2014 HIV Drug Guide

CO M M E M O R AT I N G

25

YEARS

THE 18TH ANNUAL HIV DRUG GUIDE

POSITIVELY AWARE M A R C H +A P R I L 2 0 1 4

Antiretroviral therapy in 2014 Treatment guidelines for first-timers Getting help paying for your meds Special Pull-OUT HIV DRUG CHart

DEFYING THE GRAVITY OF HIV

ABOUT PREZISTA

®

PREZISTA® is always taken with and at the same time as ritonavir (Norvir ®), in combination with other HIV medicines for the treatment of HIV infection in adults. PREZISTA® should also be taken with food.

• The use of other medicines active against HIV in combination with PREZISTA®/ritonavir (Norvir ®) may increase your ability to fight HIV. Your healthcare professional will work with you to find the right combination of HIV medicines • It is important that you remain under the care of your healthcare professional during treatment with PREZISTA® PREZISTA® does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using PREZISTA.® Please read Important Safety Information below, and talk to your healthcare professional to learn if PREZISTA® is right for you.

IMPORTANT SAFETY INFORMATION What is the most important information I should know about PREZISTA®?

• PREZISTA® can interact with other medicines and cause serious side effects. See “Who should not take PREZISTA®?”

• PREZISTA® may cause liver problems. Some people taking PREZISTA,® together with Norvir ® (ritonavir), have developed liver problems which may be life-threatening. Your healthcare professional should do blood tests before and during your combination treatment with PREZISTA.® If you have chronic hepatitis B or C infection, your healthcare professional should check your blood tests more often because you have an increased chance of developing liver problems • Tell your healthcare professional if you have any of these signs and symptoms of liver problems: dark (tea-colored) urine, yellowing of your skin or whites of your eyes, pale-colored stools (bowel movements), nausea, vomiting, pain or tenderness on your right side below your ribs, or loss of appetite • PREZISTA® may cause a severe or life-threatening skin reaction or rash. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. You should call your healthcare professional immediately if you develop a rash.

However, stop taking PREZISTA® and ritonavir combination treatment and call your healthcare professional immediately if you develop any skin changes with these symptoms: fever, tiredness, muscle or joint pain, blisters or skin lesions, mouth sores or ulcers, red or inflamed eyes, like “pink eye.” Rash occurred more often in patients taking PREZISTA® and raltegravir together than with either drug separately, but was generally mild Who should not take PREZISTA®?

• Do not take PREZISTA® if you are taking the following medicines: alfuzosin (Uroxatral®), dihydroergotamine (D.H.E.45,® Embolex,® Migranal®), ergonovine, ergotamine (Cafergot,® Ergomar ®), methylergonovine, cisapride (Propulsid®), pimozide (Orap®), oral midazolam, triazolam (Halcion®), the herbal supplement St. John’s wort (Hypericum perforatum), lovastatin (Mevacor,® Altoprev,® Advicor ®), simvastatin (Zocor,® Simcor,® Vytorin®), rifampin (Rifadin,® Rifater,®

Rifamate,® Rimactane®), sildenafil (Revatio®) when used to treat pulmonary arterial hypertension, indinavir (Crixivan®), lopinavir/ ritonavir (Kaletra®), saquinavir (Invirase®), boceprevir (Victrelis™), or telaprevir (Incivek™) • Before taking PREZISTA,® tell your healthcare professional if you are taking sildenafil (Viagra,® Revatio®), vardenafil (Levitra,® Staxyn®), tadalafil (Cialis,® Adcirca®), atorvastatin (Lipitor ®), rosuvastatin (Crestor ®), pravastatin (Pravachol®), or colchicine (Colcrys,® Col-Probenecid®). Tell your healthcare professional if you are taking estrogen-based contraceptives (birth control). PREZISTA® might reduce the effectiveness of estrogen-based contraceptives. You must take additional precautions for birth control, such as condoms This is not a complete list of medicines. Be sure to tell your healthcare professional about all the medicines you are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

What should I tell my doctor before I take PREZISTA®?

• Before taking PREZISTA,® tell your healthcare professional if you have any medical conditions, including liver problems (including hepatitis B or C), allergy to sulfa medicines, diabetes, or hemophilia • Tell your healthcare professional if you are pregnant or planning to become pregnant, or are breastfeeding — The effects of PREZISTA® on pregnant women or their unborn babies are not known. You and your healthcare professional will need to decide if taking PREZISTA® is right for you — Do not breastfeed. It is not known if PREZISTA® can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to your baby in the breast milk What are the possible side effects of PREZISTA®?

• High blood sugar, diabetes or worsening of diabetes, and increased bleeding in people with hemophilia have been reported in patients taking protease inhibitor medicines, including PREZISTA® • Changes in body fat have been seen in some patients taking HIV medicines, including PREZISTA.® The cause and long-term health effects of these conditions are not known at this time • Changes in your immune system can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden • The most common side effects related to taking PREZISTA® include diarrhea, nausea, rash, headache, stomach pain, and vomiting. This is not a complete list of all possible side effects. If you experience these or other side effects, talk to your healthcare professional. Do not stop taking PREZISTA® or any other medicines without first talking to your healthcare professional You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please refer to the ritonavir (Norvir ®) Product Information (PI and PPI) for additional information on precautionary measures.

Please read accompanying Patient Information for PREZISTA® and discuss any questions you have with your doctor.

28PRZDTC0288R8

PREZISTA® (darunavir) is a prescription medicine. It is one treatment option in the class of HIV (human immunodeficiency virus) medicines known as protease inhibitors.

ily Once-Da

Once-Daily PREZISTA® (darunavir) taken with ritonavir and in combination with other HIV medications can help lower your viral load and keep your HIV under control.

The PREZISTA® Experience isn’t just an HIV treatment.

It’s an HIV treatment experience as unique as you.

Find out if the PREZISTA® Experience is right for you.

Ask your healthcare professional and learn more at PREZISTA.com

Snap a quick pic of our logo to show your doctor and get the conversation started.

Please read the Important Safety Information and Patient Information on adjacent pages.

Janssen Therapeutics, Division of Janssen Products, LP © Janssen Therapeutics, Division of Janssen Products, LP 2014 01/14 006960-131202

IMPORTANT PATIENT INFORMATION PREZISTA (pre-ZIS-ta) (darunavir) Oral Suspension PREZISTA (pre-ZIS-ta) (darunavir) Tablets Read this Patient Information before you start taking PREZISTA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Also read the Patient Information leaflet for NORVIR® (ritonavir).

What is the most important information I should know about PREZISTA? • PREZISTA can interact with other medicines and cause serious side effects. It is important to know the medicines that should not be taken with PREZISTA. See the section “Who should not take PREZISTA?” • PREZISTA may cause liver problems. Some people taking PREZISTA in combination with NORVIR® (ritonavir) have developed liver problems which may be life-threatening. Your healthcare provider should do blood tests before and during your combination treatment with PREZISTA. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems.

• Tell your healthcare provider if you have any of the below signs and symptoms of liver problems.

• Dark (tea colored) urine • yellowing of your skin or whites of your eyes • pale colored stools (bowel movements) • nausea • vomiting • pain or tenderness on your right side below your ribs • loss of appetite PREZISTA may cause severe or life-threatening skin reactions or rash.

Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. You should call your healthcare provider immediately if you develop a rash. However, stop taking PREZISTA and ritonavir combination treatment and call your healthcare provider immediately if you develop any skin changes with symptoms below: • fever • tiredness • muscle or joint pain • blisters or skin lesions • mouth sores or ulcers • red or inflamed eyes, like “pink eye” (conjunctivitis) Rash occurred more often in people taking PREZISTA and raltegravir together than with either drug separately, but was generally mild.

See “What are the possible side effects of PREZISTA?” for more information about side effects.

What is PREZISTA? PREZISTA is a prescription anti-HIV medicine used with ritonavir and other anti-HIV medicines to treat adults with human immunodeficiency virus (HIV-1) infection. PREZISTA is a type of anti-HIV medicine called a protease inhibitor. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

When used with other HIV medicines, PREZISTA may help to reduce the amount of HIV in your blood (called “viral load”). PREZISTA may also help to increase the number of white blood cells called CD4 (T) cell which help fight off other infections. Reducing the amount of HIV and increasing the CD4 (T) cell count may improve your immune system.

This may reduce your risk of death or infections that can happen when your immune system is weak (opportunistic infections).

PREZISTA does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using PREZISTA. Avoid doing things that can spread HIV-1 infection.

• Do not share needles or other injection equipment.

• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.

• D o not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Ask your healthcare provider if you have any questions on how to prevent passing HIV to other people.

Who should not take PREZISTA? Do not take PREZISTA with any of the following medicines: • alfuzosin (Uroxatral®) • dihydroergotamine (D.H.E. 45®, Embolex®, Migranal®), ergonovine, ergotamine (Cafergot®, Ergomar®) methylergonovine • cisapride • pimozide (Orap®) • oral midazolam, triazolam (Halcion®) • the herbal supplement St. John’s Wort (Hypericum perforatum) • the cholesterol lowering medicines lovastatin (Mevacor®, Altoprev®, Advicor®) or simvastatin (Zocor®, Simcor®, Vytorin®) • rifampin (Rifadin®, Rifater®, Rifamate®, Rimactane®) • sildenafil (Revatio®) only when used for the treatment of pulmonary arterial hypertension.

Serious problems can happen if you take any of these medicines with PREZISTA. What should I tell my doctor before I take PREZISTA? PREZISTA may not be right for you. Before taking PREZISTA, tell your healthcare provider if you: • have liver problems, including hepatitis B or hepatitis C • are allergic to sulfa medicines • have high blood sugar (diabetes) • have hemophilia • are pregnant or planning to become pregnant. It is not known if PREZISTA will harm your unborn baby.

Pregnancy Registry: You and your healthcare provider will need to decide if taking PREZISTA is right for you. If you take PREZISTA while you are pregnant, talk to your healthcare provider about how you can be included in the Antiretroviral Pregnancy Registry. The purpose of the registry is follow the health of you and your baby.

• are breastfeeding or plan to breastfeed. Do not breastfeed. We do not know if PREZISTA can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Using PREZISTA and certain other medicines may affect each other causing serious side effects. PREZISTA may affect the way other medicines work and other medicines may affect how PREZISTA works.

Especially tell your healthcare provider if you take: • other medicine to treat HIV • estrogen-based contraceptives (birth control). PREZISTA might reduce the effectiveness of estrogen-based contraceptives. You must take additional precautions for birth control such as a condom.

• medicine for your heart such as bepridil, lidocaine (Xylocaine Viscous®), quinidine (Nuedexta®), amiodarone (Pacerone®, Cardarone®), digoxin (Lanoxin®), flecainide (Tambocor®), propafenone (Rythmol®) • warfarin (Coumadin®, Jantoven®) • medicine for seizures such as carbamazepine (Carbatrol®, Equetro®, Tegretol®, Epitol®), phenobarbital, phenytoin (Dilantin®, Phenytek®) • medicine for depression such as trazadone and desipramine (Norpramin®) • clarithromycin (Prevpac®, Biaxin®) • medicine for fungal infections such as ketoconazole (Nizoral®), itraconazole (Sporanox®, Onmel®), voriconazole (VFend®) • colchicine (Colcrys®, Col-Probenecid®) • rifabutin (Mycobutin®) • medicine used to treat blood pressure, a heart attack, heart failure, or to lower pressure in the eye such as metoprolol (Lopressor®, Toprol-XL®), timolol (Cosopt®, Betimol®, Timoptic®, Isatolol®, Combigan®) • midazolam administered by injection • medicine for heart disease such as felodipine (Plendil®), nifedipine (Procardia®, Adalat CC®, Afeditab CR®), nicardipine (Cardene®) • steroids such as dexamethasone, fluticasone (Advair Diskus®, Veramyst®, Flovent®, Flonase®) • bosentan (Tracleer®) • medicine to treat chronic hepatitis C such as boceprevir (VictrelisTM), telaprevir (IncivekTM)

IMPORTANT PATIENT INFORMATION • m edicine for cholesterol such as pravastatin (Pravachol®), atorvastatin (Lipitor®), rosuvastatin (Crestor®) • medicine to prevent organ transplant failure such as cyclosporine (Gengraf®, Sandimmune®, Neoral®), tacrolimus (Prograf®), sirolimus (Rapamune®) • salmeterol (Advair®, Serevent®) • medicine for narcotic withdrawal such as methadone (Methadose®, Dolophine Hydrochloride), buprenorphine (Butrans®, Buprenex®, Subutex®), buprenorphine/naloxone (Suboxone®) • medicine to treat schizophrenia such as risperidone (Risperdal®), thioridazine • medicine to treat erectile dysfunction or pulmonary hypertension such as sildenafil (Viagra®, Revatio®), vardenafil (Levitra®, Staxyn®), tadalafil (Cialis®, Adcirca®) • medicine to treat anxiety, depression or panic disorder such as sertraline (Zoloft®), paroxetine (Paxil®, Pexeva®) • medicine to treat malaria such as artemether/lumefantrine (Coartem®) This is not a complete list of medicines that you should tell your healthcare provider that you are taking. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine. Do not start any new medicines while you are taking PREZISTA without first talking with your healthcare provider.

How should I take PREZISTA? • Take PREZISTA every day exactly as prescribed by your healthcare provider.

• You must take ritonavir (NORVIR®) at the same time as PREZISTA. • Do not change your dose of PREZISTA or stop treatment without talking to your healthcare provider first.

• Take PREZISTA and ritonavir (NORVIR®) with food.

• Swallow PREZISTA tablets whole with a drink. If you have difficulty swallowing PREZISTA tablets, PREZISTA oral suspension is also available. Your health care provider will help decide whether PREZISTA tablets or oral suspension is right for you.

• PREZISTA oral suspension should be given with the supplied oral dosing syringe. Shake the suspension well before each use. See the Instructions for Use that come with PREZISTA oral suspension for information about the right way to prepare and take a dose.

• If your prescribed dose of PREZISTA oral suspension is more than 6 mL, you will need to divide the dose. Follow the instructions given to you by your healthcare provider or pharmacist about how to divide the dose. Ask your healthcare provider or pharmacist if you are not sure.

• If you take too much PREZISTA, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I do if I miss a dose?

People who take PREZISTA one time a day: • If you miss a dose of PREZISTA by less than 12 hours, take your missed dose of PREZISTA right away. Then take your next dose of PREZISTA at your regularly scheduled time.

• If you miss a dose of PREZISTA by more than 12 hours, wait and then take the next dose of PREZISTA at your regularly scheduled time.

People who take PREZISTA two times a day • If you miss a dose of PREZISTA by less than 6 hours, take your missed dose of PREZISTA right away. Then take your next dose of PREZISTA at your regularly scheduled time.

• If you miss a dose of PREZISTA by more than 6 hours, wait and then take the next dose of PREZISTA at your regularly scheduled time.

If a dose of PREZISTA is skipped, do not double the next dose. Do not take more or less than your prescribed dose of PREZISTA at any one time.

What are the possible side effects of PREZISTA? PREZISTA can cause side effects including: • See “What is the most important information I should know about PREZISTA?” • D iabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including PREZISTA can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking PREZISTA. • Changes in body fat. These changes can happen in people who take antiretroviral therapy. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The exact cause and longterm health effects of these conditions are not known.

• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Call your healthcare provider right away if you start having new symptoms after starting your HIV medicine.

• Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including PREZISTA. The most common side effects of PREZISTA include: • diarrhea • headache • nausea • abdominal pain • rash • vomiting Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of PREZISTA. For more information, ask your health care provider.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How should I store PREZISTA? • Store PREZISTA oral suspension and tablets at room temperature [77°F (25°C)].

• Do not refrigerate or freeze PREZISTA oral suspension.

• Keep PREZISTA away from high heat.

• PREZISTA oral suspension should be stored in the original container.

Keep PREZISTA and all medicines out of the reach of children.

General information about PREZISTA Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PREZISTA for a condition for which it was not prescribed. Do not give PREZISTA to other people even if they have the same condition you have. It may harm them.

This leaflet summarizes the most important information about PREZISTA. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about PREZISTA that is written for health professionals.

For more information, call 1-800-526-7736.

What are the ingredients in PREZISTA? Active ingredient: darunavir Inactive ingredients: PREZISTA Oral Suspension: hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment), purified water.

PREZISTA 75 mg and 150 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® White (polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide).

PREZISTA 400 mg and 600 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® Orange (FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide).

PREZISTA 800 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, hypromellose. The film coating contains: OPADRY® Dark Red (iron oxide red, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide).

This Patient Information has been approved by the U.S Food and Drug Administration.

Product of Ireland Manufactured by: PREZISTA Oral Suspension PREZISTA Tablets Janssen Pharmaceutica, N.V. Janssen Ortho LLC, Beerse, Belgium Gurabo, PR 00778 Manufactured for: Janssen Therapeutics, Division of Janssen Products, LP, Titusville NJ 08560 Revised: December 2013 NORVIR® is a registered trademark of its respective owner.

PREZISTA® is a registered trademark of Janssen Pharmaceuticals © Janssen Pharmaceuticals, Inc. 2006 007653-131217

POSITIVEL JOURNALISM. INTEGRITY. HOPE.

Jeff Berry

ed ito r- i n - C h i ef

Enid Vázquez

a sso c iate ed ito r

Sue Saltmarsh co py Ed ito r

Rick Guasco

C r e ative d i r ec to r

Joshua Thorne W eb M a ster

Jason Lancaster proo fr e a d er

co ntr i b u ti n g w r iters

Sal Iacopelli, Laura Jones Jim Pickett, Andrew Reynolds Matt Sharp p h oto g r a p h ers

Chris Knight Joshua Thorne a dverti s i n g

Lorraine Hayes l.hayes@tpan.com S u b sc r i pti o n s

Shelby Pollard

distribution@tpan.com

PUBLISHED BY

2014 HIV Drug Pull-out chart sponsored by

positivelyaware . com

Drug interactions chart

Potential drug-drug interactions. positivelyaware.com/2014/14-03/ interactions.shtml for a list of Walgreens HIV specialty pharmacies, and other resources, Go to HIV.walgreens.com

ON THE COVEr and on this spread Wyll Martinez photographed by chris knight.

4

POSITIVELY AWARE 5050 N. Broadway St., SUITE 300 Chicago, IL 60640-3016 phone: (773) 989–9400 fax : (773) 989–9494 email : inbox@tpan.com

HIV prevention in a pill

How an HIV treatment drug can protect against the virus.

by Heather Free, Pharm D

positivelyaware.com/2014/14-03/ truvada-as-prep.shtml

March+April 2014 | positivelyaware.com/drugguide

LY AWARE M A RC H+A P R I L 2 014

VOLUME 26

NUMBER 3

C O M M E M O R AT I N G

25

YEARS

A guide to the guide

How to navigate through these pages.

by Sue Saltmarsh

18

Defying the Gravity of HIV—

The 18th Annual HIV Drug Guide From Aptivus to Ziagen, a handbook of all the drugs used for treating HIV (and those nearing approval)—plus comments from a doctor and an activist.

Compiled by ENid VÁzquez and Patrick Clay, PharmD

24–59

Non-HIV drugs

Several drugs HIV-positive people also take.

64

Throb, yawn, scratch, and plop Potential drug side effects you should be aware of.

Compiled by AMbrose delpino, PharmD, AAHIVP

67

Departments

Feat u res

6 In Box

Antiretroviral therapy in 2014

Standard issue

How’s a doctor to choose?

DHHS guidelines for first-time therapy.

So many conditions, so many drugs

The cost of living

The ‘Cheese Guy’ speaks; Lord of the Ring.

6 Readers Poll 7 editor’s Note It’s not that complicated.

13 Contributors

14

Living longer may lead to more drug interactions.

73

76

Co-pay and patient assistance programs can help with the cost of meds.

82

March+April 2014 | positivelyaware.com/drugguide

5

I N B OX

Bob skinner’s picture for A Day with HIV has earned him a nickname.

The ‘CHEESE GUY’ SPEAKS

I sent in a picture of myself for A Day with HIV and it was published. My hope for sending it in was two-fold—first, to show that most people with HIV can and do lead a somewhat normal life; secondly, to raise more awareness by showing the diversity of this disease. I just received the new edition of PA yesterday and in the In Box, I saw that someone from my area had sent in a response to my picture. She stated that she was “shocked by the number of children, women, and straight people” that were pictured and that she saw her “cheese guy” there—that was me! I sell goat cheese at the Eugene Farmers Market in Eugene, Oregon. She went on to say, “I’ve never talked to him about HIV, but the next time I buy some of his delicious goat cheese I’ll be glad to say, ‘I saw you in Positively Aware!’ Thanks for opening our eyes.”

Now that’s some awareness.

I was also named as one of POZ magazine’s 100 “unsung heroes” and somehow our local paper caught wind of this and called me to do an interview. Of course I said yes—here was another chance to bring more awareness to my community. Little did I know that I was going to be on the front page of the paper! The interview also included a paragraph about my picture being selected as part of A Day with HIV. It is projects like these that can and do show people that HIV/AIDS does not

R ea d ers poll

discriminate. It’s not who you are but what you do. I can only hope that being part of such projects will help lower the discrimination and stigma associated with this disease and show those that think HIV/AIDS is yesterday’s news that it’s still here. Yes, we are winning the battle in some ways, but we still have a long way to go and I am in it for the long haul. I saw the beginning of this disease and my dream is to see the end.

Thank you once again for all that you do.

PA has made a difference in my life. I now have a new title “Cheese Guy”—I love it!

Here’s the article that was in our paper [The Corvallis Gazette-Times] as well as the response to my picture for A Day with HIV: gazettetimes.com/news/local/stayingpositive-with-hiv/article_0b7ea5e6-6eaf11e3-a408-001a4bcf887a.html

In the JAN+FEB issue, we asked

Do you benefit from sharing information and experiences with other HIV-positive people?

52%

Yes, very much.

26%

Yes, occasionally.

—Robert Skinner, President/CEO Valley AIDS Information Network Corvallis, Oregon

13% 9%

No, not particularly.

No, definitely not.

YO U R CO M M E N T S

“Although my status is not public knowledge, I learn so much from friends and colleagues dealing with this disease.

From my end, I have much to share, even if it is not about my own infection.”

“I find it very beneficial to talk to other people who are living with the same thing I have.”

lord of the ring

Patrick Kiser [Science and Sex, JAN+FEB issue], I knew you when you were a youngster.

You were never a ‘nerd.’ You just walked to a different drummer.

I am so proud to know someone like you.

My granddaughter is a senior at Madison, majoring in bio-medical engineering.

Congratulations to you on all of your achievements.

“Sharing information and experi-

ences with other people has made the difference in surviving with HIV.”

“I’ve been unable to find a support group to attend that includes women.

I share with my Adult Survivors of Child Abuse support group.”

—Pat Warren Lake Michigamme, Michigan

Talk back. All communications (letters, email, online posts, etc.) are treated as letters to the editor unless otherwise instructed. We reserve the right to edit for length, style, or clarity. Let us if know you prefer we not use your name and city. You can also write: Positively Aware 5050 N. Broadway St., Suite 300, Chicago, IL 60640-3016.

This issue’s question

How often do you discuss medication issues with a pharmacist? vote at positivelyaware.com or on facebook:

https://a.pgtb.me/ffPCjX 6

March+April 2014 | positivelyaware.com

E d itor ’ s note

|

Jeff Berry

IT’S NOT THAT COMPLICATED

T Photo: Joshua Thorne

his is the 18th Annual POSITIVELY AWARE HIV Drug Guide, arguably our most popular, biggest, and most technical issue of the year. When I first came on as interim editor in the fall of 2004, I had no experience as an editor and was thrown into an issue on HIV basics, followed by a special issue on pharmacokinetics (PK), while simultaneously producing the ninth annual HIV Drug Guide, all within the space of a few months. I had no idea what I was getting myself into; needless to say, my head was spinning. Not knowing any better, I took it all in stride and somehow survived the chaos, and we ended up with, if I may be so bold, three great issues of the magazine.

I owe that success to a team of dedicated professionals I worked with and who taught me the importance of hard work, patience, and attention to detail. One of those people was Patrick Clay, PharmD, who served as guest editor of the special issue on PK in the winter of 2005.

Now we have come full circle with Patrick who this year gathered a team of dedicated professionals from around the country to edit and update the content for the individual drug pages, and who served as supervising editor for the drug section of this year’s guide.

My introduction to the world of being an editor for an HIV/AIDS publication is kind of what it’s like when someone first starts therapy. All these strange terms and words are suddenly being thrown at you, and it’s all happening so fast you don’t even have time to stop and think.

You have to make some pretty quick decisions, and you need to have a certain amount of trust and confidence in those around you that they know what they’re doing.

Luckily, it doesn’t have to be that complicated. The POSITIVELY AWARE HIV Drug Guide helps decipher some of the more complex information about HIV treatment and break it down in a way people can understand and easily digest. The guide can help people who are just starting therapy, as well as those who have been on treatment for a long time, to make informed decisions about their health so they can live full and productive lives.

The drug guide also helps providers when talking with their patients and clients about living with and treating HIV. It helps them understand what some of their options might be among the therapies that are available and what to consider before starting or switching therapies. I can’t tell you how many times over the years I’ve heard from advocates and providers out in the community who tell me they have the drug chart hanging on the wall, right next to their desk!

With the more tolerable and simplified therapies

that are available today, once you’ve made your decision to start therapy and have chosen a treatment regimen, hopefully that will be as complicated as your decision-making gets. At that point, it really is all about remaining adherent to your regimen, taking the drugs as prescribed. Adherence to me is not only remembering to take each dose when I’m supposed to, but also making sure I take it with food or on an empty stomach if I need to. Otherwise, I’m not being adherent.

Adherence is about making sure that the right levels of the drug are in your body at all times to effectively fight the virus. So do whatever you have to do to make that happen—take your meds at the same time every day as prescribed; be sure not to take them with other drugs that might make them less effective or more toxic.

Commit yourself to adherence and seeing it through, so that you keep your viral load undetectable and don’t develop resistance to your medications.

A big thank you to Rick Guasco, Sue Saltmarsh, Joshua Thorne, and Enid Vázquez without whom this drug guide would not have come to fruition; Joel Gallant and Dawn Averitt for their insightful comments; Patrick Clay and all of the pharmacists who worked with us this year; and to Lorraine Hayes and Jason Lancaster for the integral parts they played!

Just as it takes more than one drug from one class to successfully control HIV, it takes the contributions of the whole PA team to produce the drug guide. Our unofficial motto could be, “This is the best drug guide ever…until next year!” We hope you think so too.

This drug guide can help people who are just starting therapy, as well as those who have been on treatment for a long time, make informed decisions about their health so they can live full and productive lives.

Follow Jeff: @PAEDITOR

Take care of yourself and each other.

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C O N T R I BU TO R S

The doctor Joel Gallant, MD, MPH Joel Gallant is Associate Medical

Director of Specialty Services at the Southwest CARE Center in Santa Fe, New Mexico, and adjunct professor of medicine in the Division of Infectious Diseases at the Johns Hopkins School of Medicine. He treats patients and conducts clinical trials on the treatment of HIV infection. He is Chair of the HIV Medicine Association, is on the Governing Council of the International AIDS Society, and the Board of Directors of the IAS-USA. He is a member of the DHHS Antiretroviral Guidelines panel and the IDSA/HIVMA HIV Primary Care Guidelines panel. He authored 100 Questions and Answers about HIV and AIDS and has an interactive question and answer blog at hivforum.tumblr.com/.

the activist Dawn Averitt Dawn Averitt was diagnosed with HIV in 1988 and is the Founder of The Well Project (thewellproject.org), a non-profit organization for HIV-positive women. She has served on the Office of AIDS Research Advisory Council (OARAC) and the President’s Advisory Council on HIV/AIDS (PACHA). Dawn has worked on several fronts increasing awareness, testing, and access to treatment. In 2003, she launched the Women’s Research Initiative on HIV/AIDS (WRI). She is a frequent speaker at conferences and universities, and has appeared on CNN, CBS, and given a TED-X Talk. Dawn was named one of 2010’s top 100 most influential AIDS activists by POZ magazine and is currently building an initiative to End AIDS in America. Dawn now lives in Vermont with her daughters and partner, Rosi.

the pharmacist Patrick G. Clay, PharmD Patrick G. Clay is currently professor

of pharmacotherapy at the University of North Texas System College of Pharmacy (UNTSCP) in Fort Worth, Texas. He has worked directly with lowincome HIV-positive people through free health clinics and research since 1996. He serves on the FDA’s Antiviral Advisory Committee and numerous National Institutes of Health (NIH) grant review panels, as well as advising the Pharmaceutical Research and Manufacturers of America (PhRMA), government and professional groups on innovative approaches to HIV treatment. He considers it an honor to find better ways to care for those with HIV, and educating them, community support groups, and healthcare professionals.

The Associate editor Enid Vázquez Associate Editor Enid Vázquez earned her journalism degree from the University of Wisconsin-Madison. Her first journalism job was reporting for the Hartford Courant, the first newspaper founded in the United States. Enid looks forward each year to updating the drug guide alongside a pharmacist who’s an expert in HIV care. She’s grateful to Dr. Patrick Clay for volunteering to work on the guide again this year—and to the 29 pharmacists who joined him to review and edit the individual drug pages. Enid welcomes comments from readers—those living with HIV and providers, case managers, and caregivers on how to improve the Drug Guide.

Co n t r i b u t i n g P h a r m ac i sts Jeffrey Abrahamson, PharmD, BCPS, AAHIVP, Methodist Dallas Medical Center; Jessica Adams, PharmD, BCPS, AAHIVP, Philadelphia College of Pharmacy, University of the Sciences; Amanda Blinkley, PharmD, AAHIVP, Penn Presbyterian Medical Center, Philadelphia; P. Brandon Bookstaver, PharmD, BCPS (AQID), AAHIVP, South Carolina College of Pharmacy, University of South Carolina, Columbia; Rodrigo Burgos, PharmD, University of Illinois at Chicago; Daniel B. Chastain, PharmD, University of Mississippi Medical Center, Jackson, MS; Tommy Chiampas, PharmD, BCPS, AAHIVP, University of Illinois at Chicago; Anne Daniels, PharmD, BCPS, AAHIVP, Froedtert Hospital, Milwaukee; Armisha Desai, PharmD, BCPS, Allegheny General Hospital, Pittsburgh; Erica Dobson, PharmD, BCPS-ID, AAHIVP, University of Rochester Medical Center; Jamie Guyear, PharmD, BCPS, AAHIVP, Kansas City (MO) Veteran Affairs Medical Center; Holly Hamilton, PharmD, Sullivan University College of Pharmacy, Louisville, KY; Emily Heil, PharmD, BCPS, AAHIVP, University of Maryland Medical Center, Baltimore; Humberto Jimenez, PharmD, BCPS, AAHIVP, JFK Medical Center, Edison, NJ; Lena Kang-Birken, PharmD, AAHIVP, FCCP, University of the Pacific School of Pharmacy and Health Sciences,

Stockton, CA; Jean Lee, PharmD, BCPS, AAHIVP, Mercy Health St. Mary’s Hospital, Grand Rapids, MI; Siyun Liao, PharmD, PhD, BCPS, University of Illinois at Chicago; Christopher McCoy, BS, PharmD, BCPS, Beth Israel Deaconess Medical Center, Boston; Andrew Merker, PharmD, BCPS, University of Illinois at Chicago; Linda Mihm, PharmD, Xavier University of Louisiana, College of Pharmacy, New Orleans; Joe Pardo, PharmD, BCPS, University of Florida Health Shands Hospital, Gainesville, FL; Shari Rosen, PharmD, Capital Health Medical Center, Trenton, NJ; Jamie Sanders, PharmD, SoutheastHEALTH, Cape Girardeau, MO; Christopher Schriever, PharmD, MS, AAHIVE, University of Illinois College of Pharmacy and Crusader Community Health Care, Rockford, IL; James D. Scott, PharmD, MEd, FCCP, AAHIVP, Western University of Health Sciences, Pomona, CA; Elizabeth Sherman, PharmD, AAHIVP, Nova Southeastern University-Fort Lauderdale and Memorial Healthcare System; Kayla Stover, PharmD, BCPS-ID, University of Mississippi School of Pharmacy, Practice site, University of Mississippi Medical Center, Jackson; Alice Tseng, BSCPHM, PharmD, FCSHP, AAHIVP, Toronto General Hospital; Velliyur Viswesh, PharmD, BCPS, California Northstate University College of Pharmacy, Sacramento.

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Antiretroviral Therapy in 2014 How does a doctor choose?

One perspective

By Joel Gallant, MD, MPH

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hile development of drugs for HIV infection has definitely slowed over the last several years, treatment options continue to expand and improve, making antiretroviral therapy (ART) easier, better tolerated, and more convenient. In this article, I’ll discuss my own opinions on options for initial therapy, and what’s in the pipeline for treatment-experienced patients.

Initial Therapy

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here’s a wealth of potential options for first-line therapy, but only a few combinations that we should actually be using on a regular basis. Speaking for myself, my “go-to” regimens for a patient starting antiretroviral therapy (ART) without baseline resistance consist of a small handful of combinations, listed here in alphabetical order:

Complera Prezista/Norvir or Reyataz/Norvir plus either Truvada or Epzicom n Stribild n Tivicay plus either Truvada or Epzicom n n

Of course, I have patients on many other first-line 14

regimens. There’s no reason to switch therapy in someone doing well on Atripla, Viramune, or Isentress, for example. But I generally stick with one of the choices mentioned above if I’m starting ART for the first time. Here’s why:

Atripla is an effective medication that has served us well for many years, but the early and usually temporary neuropsychiatric side effects (vivid dreams, dizziness, mood and cognitive changes) have always been a drawback—one that we don’t have to put up with anymore using other combinations. It’s also clear that some people have lingering side effects: depression, difficulty focusing or concentrating, or sleep changes that persist long after the more intense early side effects have resolved. These changes may be subtle, and it can sometimes be impossible to know whether they’re caused by Atripla without making a

March+April 2014 | positivelyaware.com/drugguide

THE 2014 HIV DRUG GUIDE

switch. I leave people on Atripla if they’re doing well without side effects, but I don’t use it any longer in people starting ART.

Viramune becomes a fine drug after the first month or two, but it can have potentially serious and even life-threatening toxicities during the first few weeks, especially in people with high CD4 counts. Now that we’re starting ART when CD4 counts are high, Viramune isn’t a great choice for most people. But there’s no need to switch therapy in people doing well on Viramune unless they prefer to switch to a single-tablet regimen.

Isentress is a terrific drug: it’s effective, well tolerated, and has few drug interactions. Its only downsides are that it’s taken twice a day (unlike Tivicay and Stribild) and isn’t available in a single-tablet regimen

(unlike Stribild). If you’re taking other twice-daily medications anyway, there’s no reason to switch, but for those who would prefer something more convenient, Stribild and Tivicay offer easier alternatives.

So how do I choose among my favorite regimens?

Stribild is a great choice for people who want an easy, single-tablet regimen, even if they have high viral loads or low CD4 counts. I avoid it in people with kidney disease or those who need drugs that can’t be taken with cobicistat, which is similar to Norvir in terms of drug interactions.

I sometimes use Complera in people with baseline viral loads below 100,000 and CD4 counts above 200 who want an easy, well tolerated, single-tablet regimen. Adherence is essential, of course, and it has

March+April 2014 | positivelyaware.com/drugguide

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to be taken with a meal. I avoid it in people who are taking proton pump inhibitors or H2 blockers to treat ulcers, heartburn, or reflux. I also use Complera as a “switch drug” in people on more complex regimens who want something simpler, provided they don’t have resistance to NRTIs or rilpivirine.

of a boosted PI plus either an NNRTI or an integrase inhibitor. These haven’t been well studied, and the data we have so far have been disappointing, but sometimes we just have to “wing it” (using the best available data) to avoid NRTI toxicity, hoping that we’ll soon know more about how to appropriately use regimens that don’t include NRTIs.

Prezista/Norvir or Reyataz/Norvir: I choose a PI for people whose adherence is uncertain: people with substance abuse or mental health issues, people who frequently miss clinic appointments, people with no prior experience taking long-term medications, the very young, or just the patient I don’t know well.

PIs are also recommended for those starting ART during acute infection, before resistance test results are available. There’s always the option of switching to a single-tablet regimen later, once it’s clear that there’s no resistance and the patient can adhere to therapy. However, PIs continue to get easier. This year it should be possible to take a PI-based regimen with just two pills per day: either Prezista/cobicistat or Reyataz/cobicistat plus either co-formulated Truvada or Epzicom. Of the available PIs, Prezista has the fewest side effects. Reyataz can cause jaundice, kidney stones, and gallstones, and drugs that reduce stomach acid interfere with its absorption. I may choose Reyataz for people with severe sulfa allergies, since they may be more likely to develop a rash on Prezista.

Tivicay, the newest addition, looks like a terrific drug: potent, well tolerated, easy, and with few drug interactions. Its only drawback is that it’s not available yet in a single-tablet formulation, but that will soon change when the abacavir/3TC/dolutegravir pill (see 572-Trii) is approved. Abacavir still has its issues, which I’ve discussed in my Drug Guide comments, but it will be nice to have a single-tablet combination for people who can’t take tenofovir.

The choice of NRTIs

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n my list above, those taking a PI or Tivicay have to choose between Truvada or Epzicom as their NRTI “backbone.” For people without kidney disease or osteoporosis, I choose Truvada.

I use Epzicom in people with kidney or bone disease, provided their HLA B*5701 is negative and they don’t have a lot of cardiac risk factors (hypertension, diabetes, high cholesterol, smoking, family history). The jury’s still out on whether abacavir really increases the risk of heart attack, but until we know for sure, I play it safe. Some people aren’t good candidates for any NRTI: the typical example is someone with kidney disease and either a positive HLA B*5701 or high cardiac risk. In such cases, I may use a “nuke-sparing regimen”—usually a combination

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Treatment-Experienced Patients

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ecause there are now so few people with HIV that’s “untreatable” with approved drugs, pharmaceutical companies have lost interest in developing drugs for what we used to call “salvage therapy.” Most drugs in development are intended for first-line use, because that’s where the money is. That being said, there is some good news for people with extensive drug resistance.

At double the usual dose, Tivicay is sometimes active against virus that’s resistant to Isentress and elvitegravir (the integrase inhibitor in Stribild). But the more integrase mutations you have, the less likely you are to respond to Tivicay, so don’t stay on Isentress or Stribild if they’re not keeping your viral load undetectable. Get an integrase genotype test to find out whether Tivicay will still work. If it will, get off the integrase inhibitor to avoid accumulating new mutations, and use Tivicay only when you can combine it with at least one other active drug.

Because it achieves higher tenofovir levels within cells, the investigational prodrug of tenofovir—tenofovir alafenamide fumarate (TAF)—may be active against NRTI-resistant virus, including virus that’s resistant to tenofovir DF, the current version of tenofovir (Viread), which is included in Truvada, Atripla, Complera, and Stribild.

Finally, there are new entry inhibitors in development that block the attachment of the virus to the CD4 receptor. These attachment inhibitors might eventually offer promise to people who have run out of other options.

Another bit of good news for people with drug resistance is that their regimens may soon get simpler. For example, it may not be long before someone with resistance to NRTIs, NNRTIs, and PIs could take a regimen consisting of a single tablet combination of elvitegravir, cobicistat, emtricitabine, and TAF (“son of Stribild,” if you will) plus a single tablet of Prezista. That two-tablet “salvage” regimen would be a remarkable improvement over the kinds of regimens that many treatment-experienced patients are taking now. This is just one example of how the combination of new drug development and drug coformulation may make things easier for people with drug resistance.

March+April 2014 | positivelyaware.com/drugguide

THE 2014 HIV DRUG GUIDE

Find it in print and online

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he 2014 Positively Aware HIV Drug Chart, sponsored by Walgreens, is also available as a stand-alone chart printed on heavy card-stock paper. The charts are free, but supplies are limited and orders will be filled on a first-come, first-served basis (maximum of 25 copies per order please). Email distribution@tpan.com or write/fax your request to Positively Aware, Attn.: HIV Drug Chart, 5050 N. Broadway St., Suite 300, Chicago, IL 60640; fax (773) 989-9494.

Custom URLs make it easier to go directly to the page you want to read in the online Drug Guide.

Positivelyaware.com/drugchart takes you to the online version of the HIV Drug Chart.

Positivelyaware.com/copay takes you to the co-pay and patient assistance charts starting on page 82.

Also, each drug name has its own custom URL. For example, positivelyaware.com/stribild for Stribild, or positivelyaware.com/isentress for Isentress. Go to positivelyaware.com/drugguide for the Drug Guide homepage.

Conveniently page through the digital issue of the 2014 HIV Drug Guide on your computer or mobile device, seeing it just as you would in print. Go to positivelyaware.com and click on the link, or read the digital edition at issuu.com/positivelyaware.

Positivelyaware.com also offers additional content not found in the print edition, including drug interactions and Truvada for PrEP. For additional copies of the Drug Guide, email your request: distribution@ tpan.com.

Š 2014. Positively Aware (ISSN: 1523-2883) is published bi-monthly by Test Positive Aware Network (TPAN), 5050 N. Broadway St., Suite 300, Chicago, IL 60640. TPAN is an Illinois not-for-profit corporation, providing information and support to anyone concerned with HIV and AIDS issues. Positively Aware is a registered trademark of TPAN. All rights reserved. Circulation: 100,000. For reprint permission, send email to inbox@tpan.com. Six issues mailed bulk rate for $30 donation; mailed free to those living with HIV or those unable to contribute.

We accept submission of articles covering medical or personal aspects of HIV/AIDS, and reserve the right to edit or decline submitted articles. When published, the articles become the property of TPAN, Positively Aware, and its assigns. You may use your actual name or a pseudonym for publication, but please include your name and phone number. Please include your name and phone number with your submission.

Although Positively Aware takes great care to ensure the accuracy of all the information that it presents, Positively Aware staff and volunteers, TPAN, or the institutions and personnel who provide us with information cannot be held responsible for any damages, direct or consequential, that arise from use of this material or due to errors contained herein. Opinions expressed in Positively Awaree are not necessarily those of staff or TPAN, its supporters and sponsors, or distributing agencies. Information, resources, and advertising in Positively Aware do not constitute endorsement or recommendation of any medical treatment or product. TPAN recommends that all medical treatments or products be discussed thoroughly and frankly with a licensed and fully HIV-informed medical practitioner, preferably a personal physician.

A model, photographer, or author’s HIV status should not be assumed based on their appearance in Positively Aware, association with TPAN, or contributions to this journal.

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A guide to the gu

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By Sue Saltmarsh

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ILLUSTRATION BY ABBEY DENLINGER

elow are tips to help you find your way to the knowledge you need to work with your providers and make empowered, informed choices about your treatment. Medications that are included in the HIV Drug Guide are only those drugs in the U.S. that are either FDA approved, expected to be approved this year, or those that are available through an expanded access program (EAP).

A Matter of Class There are currently five classes of anti-HIV drugs: nucleoside reverse transcriptase inhibitors (NRTIs or nukes); non-nucleoside reverse transcriptase inhibitors (NNRTIs or non-nukes); protease inhibitors (PIs); integrase strand transfer inhibitors (INSTIs); and entry inhibitors (EIs). While not a class, single tablet regimens (STRs) are grouped together too.

Anti-HIV drugs should always be taken in combination from two or more drug classes (for example, a boosted protease inhibitor plus two non-nukes).

A fixed dose combination (FDC) combines two or more drugs from the same class in one tablet, such as Epzicom (lamivudine / abacavir). A single-tablet regimen (STR) contains several drugs from different classes and is a complete regimen in one pill, such as Atripla (efavirenz / emtricitabine / tenofovir). Atripla, Complera and Stribild are the three single-tablet regimens that are now available.

When a drug is a co-formulation (combination) of several drugs, the names will be generic separated by slashes—Atripla is the co-formulation of efavirenz / emtricitabine / tenofovir.

Name that Drug Drugs are color-coded by class and are listed alphabetically within their class by brand name.

However, as you’ll see, different people know the drugs by different names.

When a drug is awaiting FDA approval, it’s given a “generic” name (such as efavirenz), which health care providers may identify it with. Once it is approved, it’s given its brand name (Sustiva is the brand name of efavirenz), which most consumers know it by. To make things even more confusing, doctors and pharmacists may refer to it by its threecharacter (letters and/or numbers) abbreviation (EFV in Sustiva’s case). Brand names are capitalized, generic names are lower case, and letters in 18

abbreviations are all caps (Sustiva, efavirenz, EFV).

Within each drug’s page, you will see the drug referred to by any or all of its names, including the “street” or common name it’s known by (such as Retrovir [zidovudine or ZDV] being commonly known as AZT). All of each drug’s names appear at the top of its page, so if you’re confused, look up there!

Viread (tenofovir) is a drug of special circumstances. It is the only “nuke” that is a nucleotide reverse transcriptase inhibitor, as opposed to nucleoside, however both types of nukes have a similar mechanism of action. Viread is also in every STR currently available, as well as being one of the two drugs in Truvada, the only drug FDA approved for PrEP. You’ll also notice that Viread is referred to by its generic name, tenofovir DF (disoproxil fumarate), but also just by “tenofovir”—another version, tenofovir alafenamide (TAF) is currently being studied. For now, whenever you see “tenofovir” without the DF, assume that it’s the DF version.

Paying the Price The Average Wholesale Price (AWP) is used by pharmacies and otherbuyers to negotiate the amount they pay for drugs. The AWP is a way to compare costs of the drugs. It is not necessarily what you would pay if you had to pay the full retail price.

HIV drugs are not cheap and with all the changes

March+April 2014 | positivelyaware.com/drugguide

THE 2014 HIV DRUG GUIDE

ide

How HIV MEDS work ENTRY INHIBITORS keep HIV out of cells either by blocking fusion to the cell’s surface or by blocking attachment to the CCR5 co-receptor.

New copies of HIV

PROTEASE INHIBITORS (PIs) block new copies of HIV from being cut into the right size proteins, preventing the new virus from being infectious.

4

1

CCR5 CO-RECEPTOR

3 INTEGRASE INHIBITORS (INSTIs) block HIV from being integrated into the cell’s DNA.

CD4 RECEPTOR

2 NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) and NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Both types of drugs stop HIV changing from a single strand of RNA into a double strand of DNA.

HIV CD4 cell in drug coverage due to the Affordable Care Act (ACA), figuring out how to pay for them can be a challenge. Luckily, there are programs that can help cover all or part of the costs and help facilitate access, though there may be some ACA-related changes there too. We’ve added information on programs for drugs used to treat hepatitis B and C, as well as several other non-HIV drugs that are often used by HIV-positive people. For a complete list of drug co-pay and patient assistance programs, see page 82.

Online Extras This year, additional information on clinical trials, post-marketing studies, charts of common side effects and drug interactions, and more will be available online at positivelyaware.com.

From Aptivus to Ziagen, you can now easily read up on each drug online by entering the drug name after our URL. For example, you’ll find the Drug Guide’s page for Prezista by typing positivelyaware. com/prezista.

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What is STRIBILD? STRIBILD is a prescription medicine used to treat HIV-1 in adults who have never taken HIV-1 medicines before. It combines 4 medicines into 1 pill to be taken once a day with food. STRIBILD is a complete single-tablet regimen and should not be used with other HIV-1 medicines.

STRIBILD does not cure HIV-1 infection or AIDS. To control HIV-1 infection and decrease HIV-related illnesses you must keep taking STRIBILD. Ask your healthcare provider if you have questions about how to reduce the risk of passing HIV-1 to others. Always practice safer sex and use condoms to lower the chance of sexual contact with body fluids. Never reuse or share needles or other items that have body fluids on them.

IMPORTANT SAFETY INFORMATION What is the most important information I should know about STRIBILD? STRIBILD can cause serious side effects: • Build-up of an acid in your blood (lactic acidosis), which is a serious medical emergency.

Symptoms of lactic acidosis include feeling very weak or tired, unusual (not normal) muscle pain, trouble breathing, stomach pain with nausea or vomiting, feeling cold especially in your arms and legs, feeling dizzy or lightheaded, and/or a fast or irregular heartbeat.

• Serious liver problems. The liver may become large (hepatomegaly) and fatty (steatosis). Symptoms of liver problems include your skin or the white part of your eyes turns yellow (jaundice), dark “tea-colored” urine, light-colored bowel movements (stools), loss of appetite for several days or longer, nausea, and/or stomach pain.

• You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking STRIBILD for a long time. In some cases, these serious conditions have led to death. Call your healthcare provider right away if you have any symptoms of these conditions.

• Worsening of hepatitis B (HBV) infection. If you also have HBV and stop taking STRIBILD, your hepatitis may suddenly get worse.

Do not stop taking STRIBILD without first talking to your healthcare provider, as they will need to monitor your health.

STRIBILD is not approved for the treatment of HBV. Who should not take STRIBILD? Do not take STRIBILD if you: • Take a medicine that contains: alfuzosin, dihydroergotamine, ergotamine, methylergonovine, cisapride, lovastatin, simvastatin, pimozide, sildenafil when used for lung problems (Revatio®), triazolam, oral midazolam, rifampin or the herb St. John’s wort.

• For a list of brand names for these medicines, please see the Brief Summary on the following pages.

• Take any other medicines to treat HIV-1 infection, or the medicine adefovir (Hepsera®).

What are the other possible side effects of STRIBILD? Serious side effects of STRIBILD may also include: • New or worse kidney problems, including kidney failure. Your healthcare provider should do regular blood and urine tests to check your kidneys before and during treatment with STRIBILD. If you develop kidney problems, your healthcare provider may tell you to stop taking STRIBILD. • Bone problems, including bone pain or bones getting soft or thin, which may lead to fractures. Your healthcare provider may do tests to check your bones.

• Changes in body fat can happen in people taking HIV-1 medicines.

• Changes in your immune system.

Your immune system may get stronger and begin to fight infections. Tell your healthcare provider if you have any new symptoms after you start taking STRIBILD. The most common side effects of STRIBILD include nausea and diarrhea. Tell your healthcare provider if you have any side effects that bother you or don’t go away.

What should I tell my healthcare provider before taking STRIBILD? • All your health problems. Be sure to tell your healthcare provider if you have or had any kidney, bone, or liver problems, including hepatitis virus infection.

• All the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. STRIBILD may affect the way other medicines work, and other medicines may affect how STRIBILD works. Keep a list of all your medicines and show it to your healthcare provider and pharmacist. Do not start any new medicines while taking STRIBILD without first talking with your healthcare provider.

• If you take hormone-based birth control (pills, patches, rings, shots, etc).

• If you take antacids. Take antacids at least 2 hours before or after you take STRIBILD. • If you are pregnant or plan to become pregnant. It is not known if STRIBILD can harm your unborn baby. Tell your healthcare provider if you become pregnant while taking STRIBILD. • If you are breastfeeding (nursing) or plan to breastfeed. Do not breastfeed. HIV-1 can be passed to the baby in breast milk. Also, some medicines in STRIBILD can pass into breast milk, and it is not known if this can harm the baby.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see Brief Summary of full Prescribing Information with important warnings on the following pages.

STRIBILD is a prescription medicine used as a complete single-tablet regimen to treat HIV-1 in adults who have never taken HIV-1 medicines before. STRIBILD does not cure HIV-1 or AIDS.

I started my personal revolution Talk to your healthcare provider about starting treatment.

STRIBILD is a complete HIV-1 treatment in 1 pill, once a day.

Ask if it’s right for you.

Patient Information STRIBILDTM (STRY-bild) (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) tablets Brief summary of full Prescribing Information. For more information, please see the full Prescribing Information, including Patient Information.

What is STRIBILD? • STRIBILD is a prescription medicine used to treat HIV-1 in adults who have never taken HIV-1 medicines before. STRIBILD is a complete regimen and should not be used with other HIV-1 medicines.

• STRIBILD does not cure HIV-1 or AIDS. You must stay on continuous HIV-1 therapy to control HIV-1 infection and decrease HIV-related illnesses.

• Ask your healthcare provider about how to prevent passing HIV-1 to others. Do not share or reuse needles, injection equipment, or personal items that can have blood or body fluids on them. Do not have sex without protection. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

What is the most important information I should know about STRIBILD? STRIBILD can cause serious side effects, including: 1. Build-up of lactic acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take STRIBILD or similar (nucleoside analogs) medicines. Lactic acidosis is a serious medical emergency that can lead to death. Lactic acidosis can be hard to identify early, because the symptoms could seem like symptoms of other health problems. Call your healthcare provider right away if you get any of the following symptoms which could be signs of lactic acidosis: • feel very weak or tired • have unusual (not normal) muscle pain • have trouble breathing • have stomach pain with nausea or vomiting • feel cold, especially in your arms and legs • feel dizzy or lightheaded • have a fast or irregular heartbeat 2. Severe liver problems. Severe liver problems can happen in people who take STRIBILD. In some cases, these liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following symptoms of liver problems: • your skin or the white part of your eyes turns yellow (jaundice) • dark “tea-colored” urine • light-colored bowel movements (stools) • loss of appetite for several days or longer • nausea • stomach pain You may be more likely to get lactic acidosis or severe liver problems if you are female, very overweight (obese), or have been taking STRIBILD for a long time.

3. Worsening of Hepatitis B infection. If you have hepatitis B virus (HBV) infection and take STRIBILD, your HBV may get worse (flare-up) if you stop taking STRIBILD. A “flare-up” is when your HBV infection suddenly returns in a worse way than before.

• Do not run out of STRIBILD. Refill your prescription or talk to your healthcare provider before your STRIBILD is all gone

• Do not stop taking STRIBILD without first talking to your healthcare provider • If you stop taking STRIBILD, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking STRIBILD Who should not take STRIBILD? Do not take STRIBILD if you also take a medicine that contains: • adefovir (Hepsera®) • alfuzosin hydrochloride (Uroxatral®) • cisapride (Propulsid®, Propulsid Quicksolv®) • ergot-containing medicines, including: dihydroergotamine mesylate (D.H.E. 45®, Migranal®), ergotamine tartrate (Cafergot®, Migergot®, Ergostat®, Medihaler Ergotamine®, Wigraine®, Wigrettes®), and methylergonovine maleate (Ergotrate®, Methergine®) • lovastatin (Advicor®, Altoprev®, Mevacor®) • oral midazolam • pimozide (Orap®) • rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®) • sildenafil (Revatio®), when used for treating lung problems • simvastatin (Simcor®, Vytorin®, Zocor®) • triazolam (Halcion®) • the herb St. John’s wort Do not take STRIBILD if you also take any other HIV-1 medicines, including: • Other medicines that contain tenofovir (Atripla®, Complera®, Viread®, Truvada®) • Other medicines that contain emtricitabine, lamivudine, or ritonavir (Combivir®, Emtriva®, Epivir® or Epivir-HBV®, Epzicom®, Kaletra®, Norvir®, Trizivir®) STRIBILD is not for use in people who are less than 18 years old.

What are the possible side effects of STRIBILD? STRIBILD may cause the following serious side effects: • See “What is the most important information I should know about STRIBILD?” • New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and while you are taking STRIBILD. Your healthcare provider may tell you to stop taking STRIBILD if you develop new or worse kidney problems.

• Bone problems can happen in some people who take STRIBILD. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do tests to check your bones.

• Changes in body fat can happen in people who take HIV-1 medicine. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms and face may also happen. The exact cause and long-term health effects of these conditions are not known.

• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.

The most common side effects of STRIBILD include: • Nausea • Diarrhea Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

• These are not all the possible side effects of STRIBILD. For more information, ask your healthcare provider.

• Call your healthcare provider for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

What should I tell my healthcare provider before taking STRIBILD? Tell your healthcare provider about all your medical conditions, including: • If you have or had any kidney, bone, or liver problems, including hepatitis B infection • If you are pregnant or plan to become pregnant. It is not known if STRIBILD can harm your unborn baby. Tell your healthcare provider if you become pregnant while taking STRIBILD. – There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.

• If you are breastfeeding (nursing) or plan to breastfeed. Do not breastfeed if you take STRIBILD. - You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.

- Two of the medicines in STRIBILD can pass to your baby in your breast milk. It is not known if the other medicines in STRIBILD can pass into your breast milk.

- Talk with your healthcare provider about the best way to feed your baby.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements: • STRIBILD may affect the way other medicines work, and other medicines may affect how STRIBILD works.

• Be sure to tell your healthcare provider if you take any of the following medicines: - Hormone-based birth control (pills, patches, rings, shots, etc) - Antacid medicines that contains aluminum, magnesium hydroxide, or calcium carbonate. Take antacids at least 2 hours before or after you take STRIBILD - Medicines to treat depression, organ transplant rejection, or high blood pressure - amiodarone (Cordarone®, Pacerone®) - atorvastatin (Lipitor®, Caduet®) - bepridil hydrochloric (Vascor®, Bepadin®) - bosentan (Tracleer®) - buspirone - carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegreto®) - clarithromycin (Biaxin®, Prevpac®) - clonazepam (Klonopin®) - clorazepate (Gen-xene®, Tranxene®) - colchicine (Colcrys®) - medicines that contain dexamethasone - diazepam (Valium®)

- digoxin (Lanoxin®) - disopyramide (Norpace®) - estazolam - ethosuximide (Zarontin®) - flecainide (Tambocor®) - flurazepam - fluticasone (Flovent®, Flonase®, Flovent® Diskus, Flovent® HFA, Veramyst®) - itraconazole (Sporanox®) - ketoconazole (Nizoral®) - lidocaine (Xylocaine®) - mexiletine - oxcarbazepine (Trileptal®) - perphenazine - phenobarbital (Luminal®) - phenytoin (Dilantin®, Phenytek®) - propafenone (Rythmol®) - quinidine (Neudexta®) - rifabutin (Mycobutin®) - rifapentine (Priftin®) - risperidone (Risperdal®, Risperdal Consta®) - salmeterol (Serevent®) or salmeterol when taken in combination with fluticasone (Advair Diskus®, Advair HFA®) - sildenafil (Viagra®), tadalafil (Cialis®) or vardenafil (Levitra®, Staxyn®), for the treatment of erectile dysfunction (ED). If you get dizzy or faint (low blood pressure), have vision changes or have an erection that last longer than 4 hours, call your healthcare provider or get medical help right away.

- tadalafil (Adcirca®), for the treatment of pulmonary arterial hypertension - telithromycin (Ketek®) - thioridazine - voriconazole (Vfend®) - warfarin (Coumadin®, Jantoven®) - zolpidem (Ambien®, Edlular®, Intermezzo®, Zolpimist®) Know the medicines you take. Keep a list of all your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. Do not start any new medicines while you are taking STRIBILD without first talking with your healthcare provider.

Keep STRIBILD and all medicines out of reach of children.

This Brief Summary summarizes the most important information about STRIBILD. If you would like more information, talk with your healthcare provider. You can also ask your healthcare provider or pharmacist for information about STRIBILD that is written for health professionals, or call 1-800-445-3235 or go to www.STRIBILD.com.

Issued: August 2012

COMPLERA, EMTRIVA, GILEAD, the GILEAD Logo, GSI, HEPSERA, STRIBILD, the STRIBILD Logo, TRUVADA, and VIREAD are trademarks of Gilead Sciences, Inc., or its related companies. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other marks referenced herein are the property of their respective owners. © 2013 Gilead Sciences, Inc. All rights reserved. QC15554 01/13

LOOK UP your HIV drug here

25 Combivir 26 Emtriva 27 Epivir 28 Epzicom 29 Retrovir 30 Trizivir 31 Truvada 32 Videx EC 33 Viread 34 Zerit 35 Ziagen

36 Edurant

NRTIs

Nucleoside / nucleotide reverse transcriptase inhibitors (“nukes”)

NNRTIs Non-nucleoside reverse transcriptase inhibitors (“non-nukes”)

37 Intelence

38 Rescriptor

39 Sustiva 40

Viramune XR

41 Aptivus

42 Crixivan 43 Invirase

44 Kaletra

PIs

Protease inhibitors

45 Lexiva

emtricitabine, or FTC lamivudine, or 3TC abacavir / lamivudine, or ABC / 3TC zidovudine, AZT, or ZDV abacavir / lamivudine / zidovudine, or ABC / 3TC / AZT emtricitabine / tenofovir, or FTC / TDF didanosine, or ddI tenofovir disoproxil fumarate [tenofovir], or TDF stavudine, or d4T abacavir, or ABC rilpivirine, or RPV etravirine, or ETR delavirdine, or DLV efavirenz, or EFV nevirapine, or NVP tipranavir, or TPV indinavir, or IDV saquinavir, or SQV lopinavir / ritonavir, or LPV / r fosamprenavir, or FPV

46 Norvir

ritonavir, or RTV

47 Prezista

48 Reyataz

49 Viracept

INSTIs

lamivudine / zidovudine, or 3TC / AZT

50 Isentress 51 Tivicay

darunavir, or DRV atazanavir, or ATV nelfinavir, or NFV raltegravir, or RAL dolutegravir, or DTG

integrase strand transfer inhibit0.ors (Integrase inhibitors)

52 elvitegravir (brand name not yet established) elvitegravir, or EVG

EIs

54 Selzentry

maraviroc, or MVC

55 Atripla

efavirenz / emtricitabine / tenofovir, or EFV / FTC / TDF

Entry inhibitors

STRs

Single-tablet regimens

PKE

“BOOSTER”

NON-HIV Other drugs 24

53 Fuzeon

56 Complera

57 Stribild

enfuvirtide, T-20, or ENF

rilpivirine / emtricitabine / tenofovir, or RPV / FTC / TDF elvitegravir / cobicistat / emtricitabine / tenofovir, or EVG / COBI / FTC / TDF

58 572-Trii

(brand name not yet established) dolutegravir / abacavir / lamivudine, or DTG / ABC / 3TC

59 cobicistat

(brand name not yet established) COBI

64 Egrifta

64 Fulyzaq

65 Serostim

tesamorelin

For HIV-related excess belly fat.

crofelemer

For HIV-related diarrhea.

somatropin [rDNA origin]

For HIV-related wasting.

March+April 2014 | positivelyaware.com/drugguide

Combivir

lamivudine / zidovudine, or 3TC / AZT NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity

More information

See the individual drugs contained in Combivir, Epivir (lamivudine) and Retrovir (zidovudine), for more details.

Side effects include nausea, fatigue, and myopathy (muscle damage). Taking with food may help decrease nausea.

Flare-up of hepatitis B upon stopping may occur (due to the withdrawal of lamivudine; see Epivir). The zidovudine in Combivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild after your regimen is changed. See page 67 for potential drug class side effects.

One head-to-head study against Truvada (emtricitabine and tenofovir) found greater toxicity with Combivir, due to anemia (see Retrovir). Under HIV treatment guidelines (DHHS), Combivir is not a preferred or alternate drug for adult men, and women who aren’t pregnant. Combivir continues to be preferred to Truvada for pregnant women who are taking therapy for the first time. Anyone taking zidovudine might consider taking Combivir instead, even if they are already resistant to the lamivudine component. Resistance to lamivudine makes HIV less fit to reproduce. It also slightly improves the antiviral activity of zidovudine and tenofovir (Viread), and for that reason, some doctors keep lamivudine onboard in combination with those drugs after resistance develops.

Although generics should be as effective and tolerable as brand name drugs, some insurers may require patients to take regimens containing generics rather than simpler brand-name, co-formulated products. For example, because both drugs in Combivir are available in generic form, insurers may require people to take separate pills of lamivudine and zidovudine rather than the fixed dose combination pill. The availability of generics might also limit choices of therapy. For example, newer brand-name drugs might be restricted to patients who can’t physically tolerate generic regimens.

See package insert for more complete information on potential side effects and interactions.

Potential drug interactions

Also see the individual drugs contained in Combivir, Epivir (lamivudine) and Retrovir (zidovudine), for more information. Do not take Combivir with Atripla, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Retrovir, Stribild, Trizivir, Truvada, or the investigational 572-Trii (a combination of Tivicay and Epzicom), since all or part of these medications are already in Combivir or they have equivalent medications. Stavudine (Zerit) cannot be taken with Combivir, as it can limit effectiveness of the zidovudine part of Combivir. Taking with ribavirin is not recommended.

STANDARD DOSE

One tablet (150 mg lamivudine / 300 mg zidovudine) twice a day (12 hours apart), with or without food, with no dietary restrictions.

Take missed dose as soon as possible, unless it is closer to the time of your next dose.

Do not double up on your next dose. Should not be used for children weighing less than 66 pounds, nor for people with kidney function less than 50 mL/min or liver disease (because the dose cannot be adjusted appropriately with this fixed dose combination). Generic is available. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872

Doctor’s comments

Activist’s comments

AWP

In the early years of HAART, Combivir was the most commonly used nucleoside “backbone” in what was often referred to as the “cocktail.” Since then it’s lost its luster: it’s taken twice a day and has the disadvantages of zidovudine (AZT) toxicity (see Retrovir). As a result, it’s been largely replaced by the safer and better tolerated once-daily co-formulations, Truvada and Epzicom.

Because the patents have expired on both AZT and 3TC (Epivir), Combivir is now available in generic form…but who cares? —Joel Gallant, MD, MPH

The first combination pill approved for HIV treatment and made available in 1997, Combivir paved the way for simpler regimens and ease of dosing. For many people, the idea of a combination pill that included AZT was easier to stomach (ironically) than AZT alone.

In addition, Combivir became the NRTI combination of choice for most pregnant women for more than a decade. Although useful in some settings, this pill has been overshadowed by newer combinations and other options. —Dawn Averitt

$1,081.70 / month; $931.61 for generic

March+April 2014 | positivelyaware.com/combivir

25

Emtriva emtricitabine, or FTC

NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE

One 200 mg capsule once a day, with or without food, with no dietary restrictions.

The dosing needs to be adjusted for children and people who have decreased kidney function.

Emtriva is very tolerable. The most common side effects (rarely seen) may include headache, diarrhea, and nausea. Flare-up of HBV (hepatitis B) in people co-infected with it and HIV has occurred when emtricitabine (Emtriva) was discontinued because it also treats HBV (see “More information”). Skin discoloration (darkening of the skin on the palms and the soles) can occur, but is generally mild and otherwise harmless. See page 67 for potential drug class side effects.

Potential drug interactions

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. It is also available as an oral solution for children from birth and older and adults who are not able to swallow the capsules. manufacturer

Gilead Sciences, Inc. gilead.com (800) GILEAD-5 (445–3235) AWP

$602.27 / month for 200 mg capsules

26

No significant drug interactions. Do not take Emtriva with Atripla, Combivir, Complera, Epivir, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, Truvada, or 572-Trii, since they contain emtricitabine or medication equivalent to it.

More information

Emtricitabine is similar to lamivudine (Epivir); both treat HIV and HBV and have the same resistance profile, meaning that if your virus is resistant to one drug, it may also be resistant to the other. However, emtricitabine remains in blood cells longer than lamivudine. Emtricitabine is active against chronic hepatitis B (though it is not FDA approved for this indication). You should never be treated only for HBV without treatment for HIV. If you have HIV and HBV and your HBV needs treatment, guidelines recommend treatment for both viruses. Emtricitabine and

tenofovir (available as one pill, Truvada) can be used as the NRTI backbone to treat HIV and HBV simultaneously.

However, there are also other HBV treatments that can be combined with HIV meds. If you are co-infected with HIV and HBV and you stop emtricitabine, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. If your HIV develops resistance to lamivudine or emtricitabine, it does not mean that your HBV is also resistant to them. Truvada is approved for HIV treatment and for HIV prevention as PrEP (pre-exposure prophylaxis; go to positivelyaware.com/2014/14-03/ truvada-for-prep.shtml). Truvada is a preferred NRTI combination in the Department of Health and Human Services (DHHS) HIV treatment guidelines for the NRTI component of first-time therapy. Sometimes, drug resistance that the virus develops against emtricitabine makes the virus less able to reproduce, meaning that it multiplies slower. It also improves the antiviral activity of zidovudine (Retrovir) and tenofovir (Viread), and for that reason, some doctors continue emtricitabine treatment in combination with other NRTIs after resistance develops.

Emtricitabine oral solution should be kept in the refrigerator. If kept at room temperature, the oral solution should be used within three months. Emtricitabine is part of the single-tablet regimens Atripla, Complera, and Stribild.

See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Like its older cousin Epivir (lamivudine), Emtriva (emtricitabine) is virtually devoid of side effects, has no drug interactions, and has the same resistance advantages. For the most part, it is used in almost any combination containing tenofovir (Viread). In fact, it probably makes sense to keep emtricitabine in any regimen containing tenofovir because the M184V mutation that causes lamivudine and emtricitabine resistance enhances the activity of tenofovir. There may be some advantages of emtricitabine over lamivudine, especially when combined with tenofovir: It remains in the blood longer after dosing and may be more potent and less prone to resistance. However, lamivudine is now available as a generic drug, and its lower price may force our hand when prescribing antiretrovirals in the future. —Joel Gallant, MD, MPH

This drug fueled the fire about the development of “me too” drugs because it is so closely related to Epivir.

At the time, there was a great deal of debate about how many NRTIs are actually needed in our HIV drug arsenal. The argument was made—successfully in this case—that even small changes, such as a longer halflife and a potentially less fit virus if resistance occurs, are actually significant over the long term clinically.

Emtriva plus Viread provided an alternative to the AZT/3TC combination of Combivir making Emtriva a far more important addition than most would have predicted. —Dawn Averitt

March+April 2014 | positivelyaware.com/emtriva

Epivir

lamivudine, or 3TC NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

Epivir is very tolerable. Side effects (though rarely seen) may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise (general ill feeling), nasal symptoms, and cough. Flare-up of hepatitis B (HBV) in people co-infected with HBV has occurred when lamivudine (Epivir) was discontinued because it also treats HBV (see “More information”). See page 67 for potential drug class side effects.

Potential drug interactions

No significant drug interactions. Do not take Epivir with Atripla, Combivir, Complera, Emtriva, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, Truvada, or 572-Trii, since they contain Epivir or medication equivalent to it.

More information

One benefit is that the drug resistance the virus develops against lamivudine (Epivir) makes the virus less able to reproduce. This mutation also slightly improves the antiviral activity of zidovudine (Retrovir or AZT) and tenofovir (Viread), and for that reason, some doctors will continue to use lamivudine after resistance develops. Lamivudine is also approved for the treatment of hepatitis B virus (HBV), under the brand name Epivir-HBV, which has a lower dose than traditional Epivir. Epivir-HBV is used only in people without HIV. It is important to note that if you have HIV and HBV, you will need to take full-dose lamivudine along with a complete HIV regimen to treat both infections. You

should never be treated only for HBV without treatment for HIV. Lamivudine and tenofovir both work against HBV and HIV and can be used together as the NRTI backbone to increase activity and decrease the risk of HBV drug resistance, but there are other HBV treatments available that can be combined with HIV meds. Truvada, for example, contains tenofovir and a medication very similar to lamivudine, formulated in one pill. If you are co-infected with HIV and HBV and you stop taking lamivudine, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. If your HIV develops resistance to lamivudine, it doesn’t mean that your HBV is also resistant to it. Lamivudine is also available in three combination products: Combivir, with zidovudine; Epzicom, with abacavir; and Trizivir, with zidovudine and abacavir. The single tablet regimen in development called 572-Trii (see page 58) contains lamivudine, abacavir, and dolutegravir (see Tivicay, page 51).

Lamivudine is available as a generic, which should be as effective and tolerable as the brand name drug Epivir.

Some insurers may require patients to take regimens containing generics rather than brand-name products.

The availability of generics might also limit choices of therapy. For example, newer brand-name drugs might be restricted to patients who can’t physically tolerate generic regimens.

See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

tenofovir and AZT, decreases the activity of abacavir.

Epivir (lamivudine, or 3TC) has been a mainstay of therapy since its approval in the mid-1990s. It’s virtually free of side effects, has no drug interactions, and has some resistance advantages. Specifically, resistance to lamivudine, occurring quickly if the viral load isn’t completely suppressed, seems to enhance the activity of zidovudine (Retrovir) and tenofovir (Viread). Lamivudine is usually used whenever abacavir (Ziagen) is used, while we tend to use its cousin emtricitabine in combination with tenofovir.

However, there is no advantage to continuing lamivudine if you’re taking abacavir but have resistance to lamivudine or emtricitabine. That’s because the M184V mutation, while enhancing the activity of

—Joel Gallant, MD, MPH

STANDARD DOSE

One 300 mg tablet once a day (or one 150 mg tablet twice daily), with or without food, with no dietary restrictions.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose is lowered for people with kidney impairment.

Dose for children 3 months to 16 years of age is 4 mg per 2.2 pounds (1 kg) twice daily to a maximum of 150 mg twice daily. A strawberry/bananaflavored liquid (10 mg/1 mL) is available.

Generic is available. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

Activist’s comments

A very potent drug that was well tolerated, Epivir was a core component of most early combination treatment regimens. Epivir made the use of AZT more tolerable for many and proved that combinations of HIV treatments would be the way of the future. Unfortunately, resistance developed quickly and although there is an added benefit of activity against hepatitis B (HBV), there is a flare-up potential for HBV co-infected patients when discontinuing Epivir. Epivir is often used as part of the NRTI backbone for pregnant women as well. —Dawn Averitt

March+April 2014 | positivelyaware.com/epivir

$498.90 / month for 300 mg tablets; $429.19 for generic

27

Epzicom

abacavir sulfate (abacavir) / lamivudine, or ABC / 3TC NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity STANDARD DOSE

One tablet (600 mg abacavir / 300 mg lamivudine), once a day, with or without food, with no dietary restrictions.

Take a missed dose as soon as possible, unless it is within 12 hours of the time of your next dose. Do not double up on your next dose. Not indicated for patients younger than 18 years old, those with kidney function less than 50 mL/min, or those with liver problems, because dose adjustments are not possible with this fixed dose combination. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$1,324.93 / month

The most common side effects of Epzicom are the same as the individual drugs it contains—see Epivir (lamivudine) and Ziagen (abacavir). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir (see Ziagen, page 35, for details of symptoms). To avoid HSR, a blood test for HLA-B*5701 (a genetic marker) can identify patients at risk for this reaction. This test is covered by most insurance (though ACA exchange plans may not cover it—check with your insurance company) and also by LabCorp/ViiV (see co-pay chart, page 84).

About 90% of HSR occurs within the first six weeks of treatment. Symptoms of HSR usually worsen, very slowly, with every dose. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom, Trizivir, Ziagen, and 572-Trii again (called “re-challenging”). Re-challenging could cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days.) Check with your doctor if you have any side effects after taking this medicine—don’t just stop! If you are co-infected with HIV and HBV and you stop Epzicom, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. Some observational studies have seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, older age, high cholesterol, and drug use), though other studies have found no increased risk.

Department of Health and Human Services (DHHS) HIV treatment guidelines state, “to date, no consensus has been reached either on the association of [abacavir] use with MI [myocardial infarction, or heart attack] risk or a possible mechanism for the association.” People who have high risk for heart disease are monitored more closely; the decision to stop or never start a regimen containing

Doctor’s comments

Epzicom is the combination of abacavir and lamivudine. It’s one of the two recommended NRTI backbones used today. Epzicom is taken once a day and is well tolerated. It has some disadvantages compared to tenofovir/emtricitabine (Truvada): Pre-testing with the HLA-B*5701 blood test is required to prevent the abacavir hypersensitivity reaction; it was less effective than Truvada in people with viral loads above 100,000 when combined with either Sustiva (efavirenz) or atazanavir/ritonavir (Reyataz/Norvir); finally, some observational studies have found evidence that abacavir may increase the risk of heart attack, especially in people with several cardiac risk factors. On the positive side, abacavir doesn’t cause the kidney toxicity sometimes seen with tenofovir; the lower effectiveness at high viral loads doesn’t apply to the combination of Epzicom plus dolutegravir (Tivicay); and the link with heart attack remains controversial because it has not been seen in all studies. In addition, a co-formulation

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abacavir is up to you and your provider. See page 67 for potential drug class side effects.

Potential drug interactions

See the individual drugs contained in Epzicom—Epivir and Ziagen—for more information. Do not take Epzicom with Atripla, Combivir, Complera, Emtriva, Epivir, EpivirHBV, Hepsera, Stribild, Trizivir, Truvada, Ziagen, or 572Trii, since all or part of these medications are already in Epzicom or contain medications equivalent to it. Other medications with major interactions include Copegus and Intron A, which can lead to side effects such as lactic acidosis and liver impairment. Tell your provider or pharmacist about all medications, herbal products, and supplements you are taking or thinking of taking, whether they are prescribed or not. Avoid use of alcohol, as it can increase the levels of abacavir and therefore increase the possibility of side effects.

More information

ViiV Healthcare applied for FDA approval late last year of a single-tablet regimen containing Tivicay and Epzicom.

In October, an update from the Department of Health and Human Services (DHHS) guidelines listed Epzicom as the preferred backbone when paired with Tivicay. Otherwise, DHHS guidelines recommend Truvada over Epzicom as the preferred backbone for the NRTI component of an HIV drug combination for first-time therapy, with Epzicom listed as an alternative NRTI backbone. The DHHS guidelines state, “Pending additional data, [Epzicom] should be used with caution in individuals who have plasma HIV RNA [viral load] greater than 100,000 copies/mL, as well as in persons at higher risk for cardiovascular disease. However, Epzicom remains a good alternative dual-NRTI option for some treatment-naïve patients.” The lamivudine portion of Epzicom is also used to treat the hepatitis B virus (HBV); see Epivir, page 27. See package insert for more complete information on potential side effects and interactions.

of abacavir, lamivudine, and dolutegravir (see 572Trii) is likely to be approved this year, making it the first single tablet regimen not containing tenofovir.

—Joel Gallant, MD, MPH

Activist’s comments

This combination pill of Epivir and Ziagen came in handy for those who could not tolerate Truvada, primarily due to kidney toxicity. Epzicom can be useful for HBV co-infected patients (although stopping Epzicom can reactiviate HBV) and those who cannot take Viread. This drug has an increasingly narrow market especially since it does not appear to be as effective in folks with higher viral loads (greater than 100,000) and its niche is somewhat nuanced. However, new life may be breathed into this drug soon in the form of a single-tablet regimen in development called 572-Trii, which contains the drugs found in Epzicom (abacavir and lamivudine) in combination with the integrase inhibitor dolutegravir (Tivicay). —Dawn Averitt

March+April 2014 | positivelyaware.com/epzicom

Retrovir

zidovudine, or AZT, or ZDV NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

May include headache, fever and chills (more common in children), muscle pain, fatigue, nausea, and fingernail discoloration. Zidovudine has been associated with alteration of various blood cells through bone marrow suppression, resulting in anemia (low red blood cell counts), which can make you feel short of breath and tired, and/ or neutropenia (low white blood cell counts), which can increase risk for getting other infections, particularly during the first three months of therapy in people with advanced HIV. Potential exists for severe anemia requiring blood transfusion, erythropoietin injections, or hospitalization. Your provider may check your blood in the first 4–6 weeks after you start zidovudine. Zidovudine is associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”).

The lipoatrophy could be irreversible or fat could take a long time to rebuild after your HIV regimen is changed.

See page 67 for potential drug class side effects.

Potential drug interactions

Do not take with Combivir or Trizivir, since zidovudine is already in these medications. Zidovudine and stavudine (Zerit) should never be used together. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Clarithromycin and rifampin may decrease zidovudine blood levels. Do not take with the cancer treatment doxorubicin. Probenecid, phenytoin, and valproic acid may increase blood levels and decrease clearance of zidovudine, but no dosing adjustments are recommended.

Bone marrow suppression should be monitored with use of ganciclovir, Valcyte, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferon-alpha, and ribavirin. Do not use ribavirin and zidovudine together, as ribavirin may decrease the effectiveness of zidovudine and increase the risk of lactic acidosis and anemia.

Measure hemoglobin once a week after starting other medications that can cause anemia until hemoglobin has stabilized. Notify your health care provider if you’re

More information

By itself, zidovudine is rarely used nowadays, though it remains the go-to medication for pregnancy and infants after birth, to prevent mother-to-child transmission.

Thanks to extensive data, zidovudine is also a preferred drug for pregnant women who are taking therapy for the first time, according to Department of Health and Human Services (DHHS) HIV treatment guidelines. Typically, zidovudine use in non-pregnant patients is rare and is mostly limited to people who have been stable on it for a long time or in salvage situations (where they have gone through other regimens and are running out of options).

You can take erythropoietin for some anemias, but that’s an expensive weekly injectable. Most doctors would prefer switching out the zidovudine for another drug. Taking with food may decrease upset stomach. Zidovudine crosses the blood-brain barrier to a useful degree, which may be beneficial for those at risk for neurological damage (such as dementia) from HIV. Although generics should be as effective and tolerable as brand name drugs, some insurers may require patients to take regimens containing generics rather than simpler brand-name, co-formulated products. For example, since both zidovudine and lamivudine (Epivir) are available in generic form, a person taking the fixed dose combination tablet Combivir might have to switch to generic lamivudine and generic zidovudine in separate pills. The availability of generics might also limit choices of therapy by insurers. For example, newer brand-name single-tablet regimens such as Stribild or Complera might be restricted to patients who can’t tolerate generic regimens. See package insert for more complete information.

Doctor’s comments

Activist’s comments

There’s still some emotional attachment to AZT (Retrovir or zidovudine), the first approved antiretroviral, and I still see the occasional patient who takes it. Personally, I haven’t found a reason to prescribe it for many years. It’s a twice-a-day drug that can cause nausea, headache, fatigue, anemia, lipoatrophy, and rarely, hepatic steatosis, and lactic acidosis. There are those who will argue its merits: It has enhanced activity in people who’ve developed tenofovir resistance with the K65R mutation, it penetrates the central nervous system well, and has a good track record for preventing mother-to-child transmission. All true, but with all the safer, more effective drugs available today, I don’t find any of those arguments persuasive.

I’d like to see AZT join d4T (Zerit) and ddI (Videx) in the NRTI wing of the antiretroviral retirement home.

The original anti-HIV drug, Retrovir (or AZT as it was known then) was a failed experimental cancer treatment that was resurrected for its antiviral activity at a time when there were no available options to fight HIV. In the early days, Retrovir was prescribed at 1200 mg per day which is twice the high-end of current dosing (300-600 mg/day) and was our first experience with the challenges of adherence (given every 4 hours around the clock) leaving it with a somewhat scarred reputation for intolerance and toxicity. That said, as with the rest of the NRTI class, Retrovir has a sordid past that includes lactic acidosis, anemia, fatigue, nausea, and links to metabolic challenges, most notably lipodystrophy. On the flip side, Retrovir was the first drug shown to reduce the risk of mother-to-child transmission of HIV by 67%, one of the great success stories in the fight against HIV. —Dawn Averitt

—Joel Gallant, MD, MPH

experiencing pain and/or swelling in the legs, worsening or shortness of breath, increases in blood pressure, dizziness, or loss of consciousness, extreme tiredness, or blood clots in hemodialysis vascular access ports.

Methadone can increase zidovudine levels—no dose adjustments are recommended, but monitor for adverse effects.

March+April 2014 | positivelyaware.com/retrovir

STANDARD DOSE

One 300 mg tablet twice a day (12 hours apart); two 100 mg capsules three times a day (8 hours apart) also available; with or without food, with no dietary restrictions.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose.

Do not double up on your next dose. Clear, strawberry-flavored liquid available for infants four weeks of age and up; dose is weight-based. If your kidney function is less than 15 mL/min or you are on dialysis, your dose will need to be adjusted. Used in pregnancy and for newborns to prevent HIV transmission from mother to child.

Generic is available. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$582.94 / month for 300 mg tablets; $360.97 for generic. $77.71 for 240 mL of 10 mg/mL syrup; $57.72 for generic

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Trizivir

abacavir sulfate (abacavir) / lamivudine / zidovudine, or ABC / 3TC / AZT NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity STANDARD DOSE

One tablet (300 mg abacavir / 150 mg lamivudine / 300 mg zidovudine), twice a day, with or without food, with no dietary restrictions.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Trizivir should not be used by those who weigh less than 88 pounds, people with weak kidney function, and those with liver disease, because dose adjustments are not possible with the fixed dose combination. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$1931.64 / month

The most common side effects of Trizivir are the same as those of the drugs it contains—see Epivir (lamivudine), Retrovir (zidovudine), and Ziagen (abacavir). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning with abacavir; see important details on Ziagen, page 35. To avoid HSR, a blood test for HLA-B*5701 (a genetic marker) can identify patients at risk for this reaction. This test is covered by most insurance (though ACA exchange plans may not cover it—check with your insurance company) and also by LabCorp/ViiV (see co-pay chart, page 84). If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as 572-Trii, Epzicom, or Ziagen, again (called “re-challenging”). Re-challenging can cause a rare life-threatening reaction. This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! It is unclear if abacavir increases the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use). People who have high risk for heart disease should be monitored more closely; the decision to stop or never start a regimen containing abacavir is up to you and your provider. Other side effects associated with Trizivir may include headache, nausea, upset stomach, and fatigue. It may be taken with food to decrease the potential nausea associated with zidovudine. The lamivudine in Trizivir will likely have an effect on hepatitis B virus (HBV) in people who are co-infected with HBV and HIV. If you are co-infected and you stop Trizivir, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. You should not stop Trizivir without first speaking with your doctor. See more details on Epivir, page 27. The zidovudine in Trizivir has been

Doctor’s comments

In the early years of the HAART era, when people were suffering on effective but complex and toxic regimens like Combivir plus Crixivan, Trizivir appeared like a breath of fresh air. Just one pill twice a day, with no need to watch the clock or time your meals, and no kidney stones, diabetes, dry skin, cracked lips, or ingrown toenails to worry about. Sure, some people developed abacavir hypersensitivity reactions (see Ziagen), and many had the usual zidovudine (AZT) side effects (see Retrovir). But compared to what we had before, it seemed almost too good to be true.

Well, it was. This “triple-nuke” regimen was shown to be less effective than a regimen containing Sustiva, both at high and low viral loads, and its use declined rapidly after that. Today, if you had some reason to be taking AZT, lamivudine, and abacavir, it would make

30

associated with anemia (low red blood cell counts) and/ or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks— sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild after changing your regimen. See page 67 for potential drug class side effects.

Potential drug interactions

See the pages for the drugs contained in Trizivir—Epivir (lamivudine), Retrovir (zidovudine), and Ziagen (abacavir), for details. Do not take Trizivir with 572-Trii, Atripla, Combivir, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir, Stribild, Truvada, or Ziagen, as all or part of these medications are already in Trizivir or it has equivalent medications. If you’re taking any of the following medications, consult your doctor or pharmacist before starting Trizivir: clarithromycin (Biaxin), Cytovene (ganciclovir), Daraprim (pyrimethamine), doxorubicin, flucytosine, Fungizone (amphotericin B), hydroxyurea, interferon, probenecid, ribavirin, rifampin, stavudine (Zerit), Valcyte (valganciclovir), Depakote (divalproex), interferon alpha, methadone, phenytoin, or sulfadiazine.

More information

Trizivir is the only triple combination NRTI that has been studied in a randomized, controlled study, which has shown it to be inferior to the standard treatment of two NRTIs plus efavirenz (Sustiva). Department of Health and Human Services (DHHS) treatment guidelines recommend that Trizivir should only be used alone if other options are not available due to toxicities or drug interactions associated with other HIV regimens. See package insert for more complete information on potential side effects and interactions.

sense to take them in the form of Trizivir, and there’s rarely a reason to take AZT. —Joel Gallant, MD, MPH Activist’s comments

The only all-NRTI triple combination regimen, Trizivir was a sign of the times when it was first approved.

Many people wanted to be free of regimens containing protease inhibitors and Trizivir created the opportunity to simplify a regimen with three drugs in one pill and avoid the PI class of drugs. The triple NRTI strategy was short-lived, showing lower efficacy without significantly reducing toxicity for most patients. The additional impact of potential hypersensitivity reactions to abacavir tipped the scales and Trizivir is really only used to simplify complex background regimens in rare cases. —Dawn Averitt

March+April 2014 | positivelyaware.com/trizivir

Truvada

emtricitabine / tenofovir, or FTC / TDF NRTI: NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITOR (NUCLEOSIDE, OR “NUKE”) | FIXED DOSE COMBINATION

Potential side effects and toxicity

See the pages for the individual drugs contained in Truvada—Viread and Emtriva. Overall, it is fairly well tolerated, but some may experience diarrhea, dizziness, nausea, depression, fatigue, insomnia, abnormal dreams, and rash. Skin discoloration on palms and soles may also occur. The tenofovir (Viread) in Truvada is associated with decreases in bone mineral density (BMD). BMD monitoring should be considered in people who have a history of bone fracture due to disease or are at risk for osteopenia or osteoporosis. It is unknown if calcium supplements with or without vitamin D would be beneficial. While calcium and vitamin D levels can be checked to assess the need for these supplements, talk with your provider before starting since many calcium supplements can affect your stomach’s acid level. Less common side effects include kidney toxicities and low blood phosphate. Tell your provider about persistent or worsening bone pain and fractures, with or without muscular pain or weakness, as these could be signs of kidney problems. If Emtriva, Viread, or Truvada are discontinued abruptly in HBV-co-infected patients, severe acute exacerbation of hepatitis may occur. See Emtriva, page 26, for hepatitis B information.

See page 67 for potential drug class side effects.

Potential drug interactions

See the pages for the individual drugs contained in Truvada—Viread and Emtriva. Do not take with 572Trii (still investigational), Atripla, Combivir, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, or Viread since all or part of these medications are already in Truvada or it contains equivalent medications.

Tenofovir decreases the concentration levels of Reyataz, therefore Reyataz must be boosted with Norvir when used in combination with tenofovir or Truvada. In addition, Reyataz and Kaletra increase tenofovir concentrations for unknown reasons. It is recommended that patients taking Reyataz or Kaletra with Truvada should be monitored for Truvada-associated adverse events, particularly

decreases in kidney function. When taken with Truvada or Viread, it is recommended that Reyataz 300 mg is taken with Norvir 100 mg (all as a single daily dose with food).

No dose adjustment is needed when used with Kaletra.

Avoid taking Truvada with drugs that negatively affect the kidneys, including Zovirax, Valtrex, and high-dose drugs like Advil, Alleve, and Motrin. Tenofovir increases levels of didanosine (Videx EC), so use with caution and make sure your dose of didanosine is adjusted accordingly and monitored for toxicities. Can be taken with Olysio (simepravir).

More information

Currently, Department of Health and Human Services (DHHS) HIV treatment guidelines recommend Truvada over Epzicom or Combivir as the preferred medication for the NRTI component for first-time therapy (unless taking Tivicay). One study reported that while both Epzicom and Truvada reduced viral load, for those people who started treatment with a viral load of more than 100,000, Epzicom was “less effective at controlling HIV” in the regimens tested. Moreover, time to a serious adverse event was sooner in the people taking Epzicom. Kidney function must be monitored before and during treatment with Truvada and it may not be a good option for patients with underlying kidney problems. The components of Truvada are contained in three single-tablet regimens taken once daily: Atripla, Complera, and Stribild. Supplementation with calcium and vitamin D has not been clearly shown to prevent bone issues in HIV patients. The FDA recommends calcium and vitamin D supplementation for all patients who need it, regardless of HIV status. Truvada was also FDA approved in July 2012 for PrEP (prevention) in HIV-negative individuals. However, awareness about proper usage is urgently needed, both for effectiveness and to avoid viral drug resistance if someone becomes infected while taking it. Go to positivelyaware. com/2014/14-03/truvada-for-prep.shtml for the use of Truvada in PrEP. See package insert for more information on side effects and interactions.

Doctor’s comments

Activist’s comments

Truvada (tenofovir combined with emtricitabine) is now the preferred nucleoside backbone for initial regimens according to DHHS and IAS-USA guidelines, based on studies showing that it’s more effective and safer than Combivir, and more effective at high viral loads than Epzicom. The two components of Truvada are also available in three single-tablet regimens: in Atripla it’s combined with efavirenz (Sustiva); in Complera it’s combined with rilpivirine (Edurant); and in Stribild it’s combined with elvitegravir and cobicistat. People taking Truvada need to be monitored for kidney toxicity (see Viread), and those who already have kidney disease may need to take Truvada less frequently than once a day, or better yet, avoid it altogether. The bone issues seen with tenofovir (Viread) also apply to Truvada. —Joel Gallant, MD, MPH

The combination of Viread and Emtriva into a single pill, Truvada, has become the cornerstone of the most widely prescribed regimens in the U.S. Truvada was swept up with much fanfare as an alternative to Retrovir or Combivir after years of struggling with the old school nukes. Truvada seems to be well tolerated, but kidney function and possible bone mineral density issues are both concerns. In any case, Truvada ushered in an age where combination pills became the standard rather than a novelty as new agents are now scrutinized in early clinical trials to determine viability for co-formulation. Gone is the tackle box assortment of pills of the early days. —Dawn Averitt

March+April 2014 | positivelyaware.com/truvada

STANDARD DOSE

For adults and children 12 years or older weighing more than 77 pounds (35 kg), one tablet (200 mg emtricitabine / 300 mg tenofovir DF) once daily, with or without food, with no dietary restrictions. Truvada should be used in HIVinfected patients only in combination with other antiretroviral agents.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. The dosing frequency needs to be adjusted for people with decreased kidney function. Truvada should not be used if kidney function is less than 30 mL/ min or if you are on dialysis. Truvada is also approved for prevention (pre-exposure prophylaxis, or PrEP) in confirmed HIV-negative adults at high risk for HIV; see online drug guide for the use of Truvada in PrEP. manufacturer

Gilead Sciences, Inc. gilead.com (800) GILEAD-5 (445–3235) AWP

$1,539.90 / month

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Videx EC didanosine, or ddI

NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE

One 400 mg entericcoated didanosine (Videx EC), delayedrelease capsule once a day for people who weigh 132 pounds or more. Take Videx EC strictly on an empty stomach (unless taking with tenofovir), one hour before or two hours after food or drink (not including water).

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose needs to be adjusted for those weighing less than 132 pounds, kidney function less than 60 mL/min, and when combined with tenofovir (Viread) or any regimens containing tenofovir. It is approved for children weighing at least 44 pounds.

Capsules must be swallowed whole. Videx is also available as a buffered powder for oral solution. Generic didanosine EC (pictured) is available.

Peripheral neuropathy (tingling, burning, numbness, or pain in the hands or feet) may go away once didanosine EC (Videx EC) is stopped, but can be painful and permanently debilitating if not treated in time or if you continue to use the drug after symptoms of neuropathy start. It occurs more frequently when didanosine EC is used with stavudine (Zerit) or in people with more advanced HIV. Upset stomach, diarrhea, headache, and, more rarely, pancreatitis (inflammation of the pancreas), have also been reported. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Body fat redistribution and accumulation have been reported. Cases of non-cirrhotic portal hypertension (increased blood pressure in the vessels that connect to and from the liver) associated with the use of didanosine EC have been reported. Symptoms (elevated liver enzymes, enlarged spleen, blood in vomit, and fluid collection in abdomen) may begin months to years after starting didanosine EC. Routine doctor visits and lab tests will assist in early detection and prompt discontinuation of didanosine.

Other possible toxicities include vision changes and optic neuritis. Periodic eye exams are recommended when taking Videx EC. Increased uric acid, alkaline phosphatase, and amylase levels are other potential side effects. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid didanosine. See a health care provider right away. You may need to stop medications. See page 67 for potential drug class side effects.

of didanosine EC when taking tenofovir to avoid didanosine-related toxicity, including neuropathy and pancreatitis. Didanosine EC dose should be decreased to 250 mg daily for patients weighing more than 132 lbs. and 200 mg daily for those weighing less. When taken with tenofovir, Videx EC may be taken with a light snack (lowfat, 400 calories). To prevent lower didanosine levels, it should be separated by two hours before or one hour after administration with atazanavir (Reyataz) or tipranavir (Aptivus). The combined use of didanosine and zidovudine, stavudine, or hydroxyurea may increase risk of peripheral neuropathy. The guidelines do not recommend administering didanosine EC and stavudine together, because of increases in the risk of facial wasting and/ or lactic acidosis. Combining Videx EC with stavudine, hydroxyurea, alcohol, valganciclovir, or intravenous (not inhaled) pentamidine may increase risk of pancreatitis.

Do not take with ribavirin or allopurinol. Also, ganciclovir substantially increases didanosine EC levels, and it’s generally recommended they not be taken together. If there is no alternative to ganciclovir, use it with caution and monitor for didanosine toxicity. Didanosine powder in oral solution should be taken on an empty stomach one hour before or two hours after protease inhibitors, cimetidine, ketoconazole, itraconazole, and dapsone, and one hour apart from delavirdine (Rescriptor). Didanosine EC capsules can be taken with them, but still on an empty stomach. Methadone decreases didanosine powder concentrations significantly and should not be used together, but if necessary, the didanosine EC capsule formulation should be used.

More information

Potential drug interactions

Based on the guidelines, Videx EC should not be taken with tenofovir (Viread) due to increases in treatment failure, adverse effects, and a decrease in CD4 count.

However, if no other options are available and coadministration is necessary, use tenofovir (or products containing tenofovir such as Atripla, Complera, Stribild, or Truvada) with caution and close monitoring since didanosine levels will be increased. Decrease the dose

Didanosine EC is rarely used. Compared to stavudine, it may have lower risk of peripheral neuropathy, but the rate found in clinical trials was still 12–34%. This is hardly an issue anymore, since stavudine is even more rarely used (if ever). The enteric coating helps reduce diarrhea. Those with reduced kidney function may require a lower dose.

Notify your doctor right away if peripheral neuropathy is suspected. See package insert for more complete information on potential side effects and interactions.

manufacturer

Bristol-Myers Squibb bms.com (800) 321-1335 AWP

$515.84 / month for 400 mg capsules; $368.72 for generic

Doctor’s comments

There’s no reason to use Videx (didanosine) anymore.

It can cause peripheral neuropathy, lipoatrophy, hepatic steatosis, and the potentially fatal complications of pancreatitis, lactic acidosis, and non-cirrhotic portal hypertension. —Joel Gallant, MD, MPH Activist’s comments

The second drug to be approved to treat HIV, ddI (Videx) has a long history of formulation changes and strategies to address intolerance, side effects,

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dosing, and toxicity management. In short, the early “hockey-puck” version of ddI involved chewing a large chalky disk which sucked all the moisture out of your mouth as you tried to choke it down dry—oh, and on an empty stomach as well. So, the latest formulation, Videx EC, for those still using this drug, is a welcome change despite the food restrictions which are still in place. The liver toxicities and peripheral neuropathy are enough to move most people on to other treatment choices. —Dawn Averitt

March+April 2014 | positivelyaware.com/videx

Viread

tenofovir disoproxil fumarate (tenofovir), or TDF NtRTI: Nucleotide reverse transcriptase inhibitor (nucleotide, or nuke)

Potential side effects and toxicity

Overall, Viread is fairly well tolerated; however, some may experience headache, diarrhea, pain, depression, nausea, weakness, and gas. Decreases in bone mineral density (BMD) have been observed. BMD monitoring should be considered in people who have a history of bone fracture due to bone disease or are at risk for osteopenia or osteoporosis. Estimated creatinine clearance (CrCl) should be assessed before initiating treatment with Viread. CrCl, glucose and protein in the urine, and serum phosphorus should be monitored more often in patients at risk for kidney problems. Less common side effects of Viread include kidney toxicities and low blood phosphate. Tell your provider about persistent or worsening bone pain and fractures, with or without muscular pain or weakness, as these could be signs of kidney problems. Since Viread is not metabolized by the liver (and appears to have less toxicity in the liver than the majority of the NRTIs), it is believed there should be minimal impact on individuals with liver disease. See page 67 for potential drug class side effects.

Potential drug interactions

Do not take Viread with Atripla, Complera, Hepsera, Stribild, or Truvada, since tenofovir is in these drugs or they contain a similar medication. Viread decreases the concentration levels of Reyataz. Therefore, Reyataz must be boosted with Norvir when used in combination with tenofovir or Truvada. Both Reyataz and Kaletra increase Viread levels. Higher Viread levels could increase the risk of Viread-associated adverse events (side effects), including kidney disorders. Patients taking Reyataz and tenofovir should be monitored for Viread-associated negative side effects. When Reyataz is taken with Viread, the dose of Reyataz is 300 mg and has to be taken with Norvir 100 mg (all as a single daily dose with food). No dose adjustment is needed when used with Kaletra.

Didanosine (Videx) levels are increased with Viread; therefore, use with caution and make sure your didanosine dose is adjusted accordingly and monitored for toxicities. Didanosine EC dose should be decreased to 250 mg daily for patients who weigh more than 132 pounds

(60 kg) and 200 mg daily for those less weighing less.

Avoid taking Viread with drugs that negatively affect the kidneys, including Zovirax, Valtrex, and high-dose or multiple NSAIDS (non-steroidal anti-inflammatory drugs, such as Advil, Aleve, and Motrin). No dose adjustment with Olysio or Sovaldi. Incivek increases Viread levels, so you and your medical provider should monitor closely for Viread side effects.

More information

Tenofovir (Viread) combined with emtricitabine (Emtriva), as Truvada, is considered the preferred NRTI combination

by DHHS HIV treatment guidelines for first-time therapy.

Tenofovir was approved in 2012 as part of Truvada for HIV prevention as PrEP (pre-exposure prophylaxis); go to positivelyaware.com/2014/14-03/truvada-forprep.shtml. The body clears most of tenofovir through the kidneys and the dosing interval needs to be adjusted for those with impaired kidney function. Serious kidney problems have been rare and mostly in those with preexisting kidney disease or taking kidney-toxic drugs. Two large observational studies found a greater risk of kidney toxicity with Viread than with other HIV meds. It is recommended that individuals with impaired kidney function be monitored closely. A large observational study published in AIDS last year discussed the negative effects on the kidneys (go to reference at positivelyaware.com/viread).

Remember that HIV itself has a negative effect on kidneys and bones. Tenofovir is FDA approved for use by itself for hep B treatment, but should not be used alone by people with both hep B and HIV. If your hep B needs treatment but your HIV doesn’t, the guidelines recommend treatment for both. If your HIV develops resistance to tenofovir and/or emtricitabine, it doesn’t mean that your HBV is also resistant to them. Tenofovir may have prolonged activity against hepatitis B even when resistant to Epivir. If you have HIV and HBV and you stop tenofovir, you may experience symptoms of acute HBV. You should be closely monitored by your physician. The FDA noted that calcium and vitamin D supplements may be beneficial for all patients taking Viread. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

that it may be safer for both bones and kidneys.

Usually a “go to” NRTI for people with healthy kidneys, tenofovir (Viread) is used in all three of the currently available single-tablet regimens. One drawback is the potential for kidney damage, which is more common in people taking tenofovir with protease inhibitors, those with pre-existing kidney problems, or people taking other drugs that damage kidneys. Kidney function and urinalysis should be monitored periodically in people taking tenofovir. Also, while all regimens containing NRTIs cause an early loss in bone mineral density during the first months of therapy, the loss is somewhat greater with tenofovir, which can be a problem when it’s taken by older people or those who already have osteopenia or osteoporosis. A newer version of tenofovir, tenofovir alafenamide fumarate (TAF), is being studied in clinical trials. There’s early evidence

—Joel Gallant, MD, MPH

STANDARD DOSE

One 300 mg tablet once a day, with or without food, with no dietary restrictions.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Dosing frequency needs to be adjusted for people with decreased kidney function. One 150 mg, 200 mg, or 250 mg once a day for children ages 2 or older weighing at least 37 pounds. Oral powder formulation available for children ages 2 and up. FDA approved for chronic HBV in patients 12 years and older. manufacturer

Gilead Sciences, Inc. viread.com (800) GILEAD-5 (445–3235) AWP

$1,047.73 / month

Activist’s comments

The story of Viread is pretty remarkable. Gilead’s wonder drug to fight HIV, now both as treatment and prevention, was approved by the FDA only after their initial drug was rejected. Fortunately, Gilead didn’t hang it up on that rejection and kept working to develop Viread.

This drug is well tolerated, but isn’t ideal for those with kidney trouble, and possibly bone density issues.

Although we will learn more with time (as we do with every drug), today Viread, either as a single drug pill or as a component of three single-tablet regimens and one fixed-dose combination, is the most widely used NRTI in the HIV arena because of its relative tolerability, effectiveness, and ease of use. —Dawn Averitt

March+April 2014 | positivelyaware.com/viread

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Zerit

stavudine, or d4T NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE

One 40 mg capsule twice a day for people weighing 132 pounds or more, or one 30 mg capsule twice a day for people weighing less; with or without food, with no dietary restrictions.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Stavudine is FDA approved for children from birth on. Stavudine is also available in 15 mg, 20 mg, 30 mg, and 40 mg capsules, and a 1 mg/mL fruit-flavored powder for oral solution (200 mL bottle) which should be shaken vigorously prior to use.

If needed, the capsules may be opened and sprinkled on 30 mL of applesauce or yogurt.

Dose reduction is needed in people with kidney problems.

A generic formulation is available. manufacturer

Bristol-Myers Squibb bms.com (800) 321-1335

Headache, diarrhea, nausea, rash, and peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) are the most common side effects. Peripheral neuropathy is more common in people who have more advanced HIV, other diseases (like diabetes or autoimmune conditions, for example) or who are taking other medications that can cause peripheral neuropathy. It tends to go away once stavudine (Zerit) is stopped, but it can be painful and permanently debilitating if stavudine is not stopped as soon as neuropathy is noticed. Caregivers of young children should be instructed on noticing and reporting peripheral neuropathy. There can be greater lipoatrophy (facial wasting) and mitochondrial toxicities when combined with didanosine (Videx EC), therefore these two medications should not be taken together.

Adverse reactions and serious laboratory abnormalities in children were similar in type and frequency to those seen in adults. Pancreatitis (inflammation of the pancreas) can be life-threatening; symptoms include pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, alcohol use, and very high triglycerides (fat in the blood).

Your physician will check for pancreatitis by doing blood tests and may have you stop all HIV medications, if necessary. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid stavudine.

Lipoatrophy, fat loss in the face, arms and legs and, to a lesser degree, lipohypertrophy (such as “buffalo hump” and increased abdominal fat) have been associated with stavudine. Stavudine and zidovudine (Retrovir, or AZT) are the HIV drugs most implicated by studies as causing lipoatrophy. Stavudine also seems to be associated with

Doctor’s comments

Zerit (stavudine) is a drug that served nobly in its time, but it should now be permanently retired. Toxicity includes peripheral neuropathy, lipoatrophy, hepatic steatosis, and potentially fatal lactic acidosis. There’s nothing it can do that safer drugs can’t do better.

—Joel Gallant, MD, MPH

AWP

Activist’s comments

$553.12 / month for 40 mg capsules; $410.70 for generic

In early HIV drug development, Zerit (d4T) was a

34

blood lipid (fat) increases, particularly triglycerides. See page 67 for potential drug class side effects.

Potential drug interactions

When used in combination with stavudine, drugs such as didanosine (Videx EC), dapsone, foscarnet (Foscavir), and amphotericin B (Fungizone) may increase the risk of developing peripheral neuropathy. Ganciclovir (Cytovene), didanosine, intravenous pentamidine (Pentam), and valganciclovir (Valcyte) may increase the risk of pancreatitis. Should be used with caution by people with pre-existing bone marrow suppression, kidney problems, or peripheral neuropathy. Zidovudine and stavudine should not be used together due to evidence that one limits the other’s effectiveness. Because of additive neurotoxicity, stavudine should not be combined with didanosine.

More information

From the pediatric to adult population, stavudine is rarely—if ever—used in the U.S., due to its toxicity and the availability of newer HIV medications. Contact your health care provider immediately if peripheral neuropathy is suspected, but do not stop taking medication unless directed to do so by your health care provider.

Studies show that stavudine crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Stavudine is associated with facial wasting, peripheral neuropathy, and pancreatitis, and many leading HIV advocates are adamant that it should be avoided because of these serious, and relatively common, toxicities. See package insert for more complete information on potential side effects and interactions.

golden child—an alternative to AZT that seemed to be far less toxic. Unfortunately, time has shown that Zerit has some serious and significant toxicities that took time to unfold. The staggering thing is that although very few people use Zerit in the global North, resource-poor countries have used the generic form of Zerit as first line therapy predominantly due to cost.

Fortunately, this is beginning to change—but only after repeating the problems already discovered and experienced in the U.S. and Europe. —Dawn Averitt

March+April 2014 | positivelyaware.com/zerit

Ziagen

abacavir sulfate (abacavir), or ABC NRTI: nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

Approximately 5–8% of people who took abacavir experienced hypersensitivity reaction (HSR), an allergic-like reaction. To avoid HSR, a blood test for HLA-B*5701 (a genetic marker) can identify patients at risk for this reaction. This test is covered by most insurance (though ACA exchange plans may not cover it—check with your insurance company) and also by LabCorp/ViiV (see co-pay chart, page 84). If the HLA-B*5701 test is positive, you would likely have HSR if you started taking abacavir. An allergy to it should be entered in your medical record. If you start abacavir without having the HLA-B*5701 test done, you should be monitored closely the first six weeks or so (HSR usually occurs within that time). Symptoms of HSR usually include some co66mbination of the following: fever, skin rash, malaise (general ill feeling), severe nausea, headache, muscle ache, chills, diarrhea, vomiting, abdominal pain, respiratory symptoms (cough, difficulty breathing, sore throat), and/or joint pain. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. HSR might be confused with flu, but symptoms of HSR usually worsen, very slowly, with every dose.

People who think they are experiencing HSR must be evaluated by an experienced HIV provider right away before they stop taking abacavir. Do not use a skin patch test to confirm HSR. Symptoms resolve quickly (24–48 hours) after permanent discontinuation. If you develop HSR, abacavir should be stopped and you can never take abacavir or any product containing abacavir (Epzicom, Trizivir, or 572-Trii) again (called re-challenging).

Re-challenging can cause a rare life-threatening reaction.

This does not apply to missed doses when there is no HSR, but watch for symptoms if you’ve stopped the drug for a few days.

Doctor’s comments

Ziagen (abacavir) is a well-tolerated drug that is typically combined with lamivudine as Epzicom, or with lamivudine and AZT as Trizivir. While it has few side effects, it has some disadvantages—pre-testing with the HLA-B*5701 blood test is required to prevent the abacavir hypersensitivity reaction and people with a positive test should never take abacavir in any of its forms (Ziagen, Epzicom, Trizivir, or 572-Trii). It was less effective than Truvada in people with viral loads above 100,000 when combined with either Sustiva (efavirenz) or Reyataz/Norvir (atazanavir/ritonavir), and finally, some observational studies have found evidence that abacavir may increase the risk of heart attack, especially in people with several risk factors. On the positive side, abacavir doesn’t cause the kidney toxicity sometimes seen with tenofovir; the lower effectiveness at high viral loads doesn’t apply to the combination of Epzicom plus dolutegravir (572-Trii); and the link with heart attack remains controversial because it has not been seen in all studies. Personally, I use abacavir mostly for patients who

Check with your doctor if you have any side effects after taking this medicine—don’t just stop! More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, trouble sleeping, unusual dreams, and anorexia (loss of appetite). Some observational studies seem to suggest that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with risk factors (such as older age, smoking, diabetes, high blood pressure, high cholesterol, and drug use). Multiple studies have looked at the association between abacavir use and the risk for heart attack, but to date no consensus has been reached on the association of abacavir with cardiac risk or a possible mechanism for the association. People who have high risk for heart disease are monitored more closely and the decision to stop or never start a regimen containing abacavir is of course up to you and your provider. See page 67 for potential drug class side effects.

Potential drug interactions

Do not take with Epivir, Epzicom, Trizivir, or 572-Trii, since abacavir is already in these medications. Excessive alcohol increases abacavir levels and may increase side effects.

More information

It is recommended that people with symptoms of acute respiratory disease consider HSR even if another diagnosis such as pneumonia, bronchitis, or flu is possible.

FDA researchers reported finding a mechanism for autoimmune drug reactions, including abacavir HSR, and hope it helps improve drug safety in the future. Abacavir is part of Epzicom and the investigational 572-Trii; see those pages. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE

Adults: two 300 mg tablets once a day (or one 300mg tablet twice a day), with or without food, with no dietary restrictions.

Children’s dose varies with age and weight.

Scored tablets and strawberry-banana flavored liquid available (may be used for children as young as 3 months).

Dose adjustment is not needed for people with kidney impairment.

Dose adjustment is needed for people with mild liver disease.

Abacavir should not be used for people with moderate or severe liver disease.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose.

Do not double up on your next dose. manufacturer

ViiV Healthcare are negative for HLA-B*5701 and who have impaired kidney function but are at low risk for heart disease.

Taking abacavir in the form of Trizivir, which combines it with AZT and 3TC, is no longer recommended, both because it contains AZT and because the triple-NRTI regimen is less effective than standard regimens.

—Joel Gallant, MD, MPH

viivhealthcare.com (877) 844-8872 AWP

$670.37 for 60 tablets; $602.66 for generic; $176.23 for 240 mL solution (20mg/mL)

Activist’s comments

The community had high hopes for Ziagen when it was first being developed because it was finally a potent, once-a-day NRTI that would make dosing easier and regimens more effective. However, the discovery of a rare but serious hypersensitivity reaction and the subsequent development of diagnostic screening to precede treatment dashed our hopes. In more recent years there has been some concern that Ziagen may also cause heart problems so we have another niche drug that may be worth investigating if other options don’t pan out, but not the homerun backbone agent many were hoping for. —Dawn Averitt

March+April 2014 | positivelyaware.com/ziagen

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Edurant

rilpivirine hydrochloride (rilpivirine), or RPV NNRTI: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity STANDARD DOSE

One 25 mg tablet once daily with a meal.

Take missed dose as soon as possible with a meal, unless it is closer to the time of your next dose. Do not double up on your next dose.

For proper absorption, it must be taken with a meal that you chew, not nutritional drinks or protein shakes, and it should have some fat. Meal examples include two slices of whole wheat toast with peanut butter and fresh fruit; a roast beef sandwich on a hard roll with mayo; or pasta and meat sauce with salad. Taking Edurant without food could result in a 40% decrease in the drug absorption and may lead to HIV resistance. manufacturer

Janssen Therapeutics janssentherapeutics.com (800) JANSSEN (526-7736)

Insomnia, headache, rash, and depressive disorders.

Tell your doctor right away if you experience negative or suicidal thoughts or actions. Nephrotic syndrome (a kidney disorder) was added to the label, noting that the level of risk is unknown, and that the syndrome may not even be related to rilpivirine (Edurant). Two different studies comparing Edurant to Sustiva showed that Edurant was slightly better tolerated. Edurant also has minimal negative effects on “bad” cholesterol, total cholesterol, and triglycerides when compared to Sustiva.

Edurant improved “good” cholesterol slightly less than Sustiva. Liver problems can occur with Edurant (even in patients without a history of liver disease). See page 68 for potential drug class side effects.

Potential drug interactions

Non-nukes interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Edurant should not be taken with other non-nukes or Complera, as the latter contains rilpivirine. Can be taken with Isentress without dose adjustments. Antacids should be taken two hours before or at least four hours after Edurant. Acid-reducing drugs (Pepcid, Tagamet, Zantac, and Axid) should be taken 12 hours before or four hours after an Edurant dose. Proton pump inhibitors (Aciphex, Nexium, Prevacid, Protonix, and Prilosec) should not be taken. Cannot be taken with the anti-seizure medications carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the anti-TB drugs rifabutin, rifampin, and rifapentine; or the herb St. John’s wort. Do not take with more than one injectable dose of the steroid dexamethasone (repeated topical use is okay). Monitor for worsening of any fungal infections when Edurant is used with anti-fungal medications like fluconazole,

itraconazole, ketoconazole, posaconazole, and voriconazole; dose adjustment for these medications may be needed. Use azithromycin when possible instead of the antibiotics clarithromycin, erythromycin, and telithromycin. Methadone levels are reduced slightly and patients should be monitored for symptoms of withdrawal. Should be used with caution when taken with medications with a known risk of Torsade de Pointes or QT prolongation (these abnormal heart rhythms can make the heart stop).

No dose adjustment needed with hepatitis C medications Olysio (simeprevir) and Sovaldi (sofosbuvir). Increase monitoring for side effects when using Incivek (telapravir) and Victrelis (boceprevir).

More information

Edurant is not recommended for patients with a viral load of greater than 100,000 copies/mL. ECHO and THRIVE studies showed that Edurant is non-inferior (a term used in scientific research that means the drug is no better or worse than those it’s compared to) to Sustiva in efficacy. Go to positivelyaware.com/edurant for more information. While its tolerability and safety profiles are advantages for Edurant, the greater potential for virologic failure in patients with high viral loads, and cross-resistance to the other NNRTIs puts Edurant at a disadvantage for first-time treatment (because patients may not be able to switch to another NNRTI if their HIV develops NNRTI resistant mutations to Edurant). Edurant is a tiny pill about the size of a baby aspirin. While Sustiva is associated with a risk of birth defects, Edurant is Pregnancy Category B (found safe in animal studies), but no human studies have been conducted. Edurant should be used in pregnancy only if the potential benefit justifies the potential risk. Most HIV medications are Pregnancy Category B and carry the same warning. See package insert for complete information on potential side effects and drug interactions.

AWP

$923.47 / month

Doctor’s comments

Edurant (rilpivirine) is the most recent addition to the NNRTI class. It’s most often taken combined with emtricitabine and tenofovir in the form of Complera, a single-tablet regimen, and it has the advantages of being extremely well tolerated with few drug interactions. When compared head-to-head against Atripla, it appeared to be as effective and better tolerated, but with some caveats. In those with viral loads well above 100,000 there was more virologic failure and resistance, including cross-resistance to Intelence (etravirine), which you don’t see after failure of efavirenz (Sustiva). For that reason, rilpivirine is recommended only for those with baseline viral loads below 100,000.

It also looks like a good “switch drug”: People whose viral load was already fully suppressed on Atripla or regimens containing a PI did well when they switched to rilpivirine, and with switches, the baseline viral load

36

doesn’t seem to matter. Rilpivirine should be taken with a meal. Drugs that block stomach acid (H2 blockers, proton pump inhibitors, and antacids) can also block the absorption of the drug. —Joel Gallant, MD, MPH Activist’s comments

The most recently approved NNRTI, Edurant is a well tolerated, if a bit finicky, typical non-nuke. This means that it has to be taken with a meal (that you eat, not drink), it should be used at just the right time (first viral load blip on another NNRTI), and it has the usual list of no-no’s (or tentative maybe’s) for drug interactions including antacids, proton pump inhibitors, anti-seizure meds, and anti-fungals to name a few. The upside is that it is an alternative to Sustiva for those who can’t tolerate that. There are no data on pregnancy, so women who may become pregnant should be aware of what we don’t know. —Dawn Averitt

March+April 2014 | positivelyaware.com/edurant

Intelence etravirine, or ETR

NNRTI: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity

Generally tolerable, but most common (though rare) side effects include rash and peripheral neuropathy. The FDA advises, “Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, malaise [general ill feeling], fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis [eye inflammation], facial edema [swelling], hepatitis, and eosinophilia [increased levels of the white blood cells called eosinophils, a sign of an allergic reaction]).” In addition, levels of liver enzymes called transaminases should be monitored. Rash is associated with all of the current NNRTIs, but if you develop a rash from Intelence, you may still be able to take one of the other NNRTI. See page 68 for potential drug class side effects.

Potential drug interactions

NNRTIs have the potential to interact with many other drugs. Refer to package insert for complete list. Tell your provider or pharmacist about all medications, herbal products, and supplements you are taking or thinking of taking, prescribed or not. Intelence should not be taken with other NNRTIs or medications that contain them (Atripla and Complera). If Intelence is taken in combination with a protease inhibitor, it must be boosted with low dose Norvir. Avoid Intelence in combination with the following PIs: Aptivus, Lexiva, Reyataz, or full-dose Norvir.

It can be taken with the integrase inhibitor Isentress with no adjustments necessary, however, should be avoided with Ticivay unless administered with one of the following combinations: Reyataz/Norvir, Prezista/Norvir, or Kaletra. Taking it in combination with Selzentry requires a Selzentry dose adjustment to 600 mg twice daily when used without a boosted PI. Adjust Selzentry dose to 150 mg twice daily if taken with both Intelence and a Norvirboosted PI. In people who’ve failed therapy with other NNRTIs, Intelence should not be taken with NRTIs alone.

Do not take Intelence with Tegretol (carbamazepine), Luminal (phenobarbital), Dilantin (phenytoin), Priftin (rifapentine), Rifadin (rifampin), or the herb St. John’s

Doctor’s comments

Intelence (etravirine) was the first “second-generation” NNRTI, meaning that it has activity in people who have become resistant to Sustiva (efavirenz) and Viramune (nevirapine). That’s not always true—there are some resistance mutations, especially nevirapine mutations, that can cause cross-resistance to Intelence—but for the most part it’s an excellent drug for people with NNRTI resistance. It’s too bad we don’t know more about using etravirine for initial therapy. It hasn’t been studied adequately as a first-line agent and isn’t approved for that indication, but it’s well tolerated, and resistance doesn’t happen as readily as with the other NNRTIs. A drawback is twice-daily dosing with a big chalky tablet that starts to dissolve as soon as it hits your mouth, but once-daily dosing is probably fine

wort. Use with caution when combined with antifungals (Diflucan and Vfend). Dosage adjustments of certain cholesterol medications may be needed based on clinical response including: Lipitor, Lescol, Mevacor, Livalo, and Zocor.

Monitor the effectiveness of Coumadin (warfarin) and adjust dose as needed based on clinical response.

Alternatives to Plavix should be considered when used with Intelence. Alternatives to clarithromycin, such as azithromycin, should be considered for treatment of MAC. Lower Valium dose may be needed. Use caution with systemic dexamethasone or consider alternatives. Intelence can be taken with Mycobutin 300 mg daily; however, it should be avoided by those who are taking a boosted PI. No interactions were found between Intelence and proton pump inhibitors Prilosec, or the acid reducer Zantac.

Intelence can be safely combined with methadone with additional monitoring for potential signs of withdrawal.

Intelence can also be safely combined with Viagra, Cialis, and Levitra, though a dosage adjustment may be necessary. Taking with Olysio is not recommended.

More information

This second-generation drug was developed to have a higher genetic barrier (more than one virus mutation) to drug resistance. It has shown significant viral load reduction in people with drug resistance to Sustiva or Viramune.

The older NNRTIs can develop resistance quickly, requiring only one viral mutation. For patients who have had virologic failure on an NNRTI-containing regimen, do not use Intelence in combination with a nucleoside backbone alone. Although not FDA approved, some providers are prescribing Intelence once daily to increase patient adherence. Some patients complain of hard-to-swallow, large chalky pills; see dissolving instructions in dose section and more commentary at positivelyaware.com/intelence.

Comparative studies between the 100 mg and 200 mg tablets showed a high rate of patient preference for the 200 mg tablets as they are dissolvable and thus, easier to swallow. Refer to package insert for complete information on potential side effects and interactions.

based on the long half-life of the drug. The tablets can also be dissolved in water (which raises the question of whether once-daily Truvada plus dissolved etravirine could be considered a “single-tablet regimen”?)

STANDARD DOSE

One 200 mg tablet, or two 100 mg tablets, twice a day, with food.

25 mg tablets available for children 6–18 years old (dose based on weight).

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. People unable to swallow pills can dissolve tablets in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication, stir well until the water looks milky, add more water if desired can use orange juice or milk as an alternative (always placing tablets in water first). Avoid grapefruit juice and warm (over 104° F) or carbonated beverages. Drink it immediately, rinse the glass several times with water, orange juice, or milk and completely swallow the rinse each time to make sure the entire dose is taken. manufacturer

Janssen Therapeutics janssentherapeutics.com (800) JANSSEN (526-7736) AWP

$1,123.52 / month

—Joel Gallant, MD, MPH

Activist’s comments

The NNRTI class was originally plagued by a common resistance pattern making the whole class a oneshot deal. Intelence changed this picture, remaining sensitive even with the standard NNRTI mutation.

Although some complain about the twice-a-day dosing schedule, for many this is not problematic (especially now that there is a 200 mg pill) and is worth the trouble to have an option other than an NRTI to use.

—Dawn Averitt

March+April 2014 | positivelyaware.com/intelence

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Rescriptor delavirdine, or DLV

NNRTI: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity STANDARD DOSE

Rarely prescribed; original full dose is two 200 mg tablets or four 100 mg tablets three times a day (every 8 hours).

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Take with or without food. Only the 100 mg tablets can be dissolved in liquid. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$432.66 / month for 200 mg tablets

Most common side effects are elevated liver enzymes and itchy skin or a rash which can be life-threatening. Most rashes occur one to three weeks after starting Rescriptor.

Patients who experienced a rash with Viramune (nevirapine) or another NNRTI are more likely to experience a rash with Rescriptor. In rare situations, if you experience blistering, mouth lesions, conjunctivitis (redness or inflammation of the eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or malaise (general ill feeling), you should stop the medication, and seek medical attention right away. See page 68 for potential drug class side effects.

Potential drug interactions

Non-nukes interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. You should not take Rescriptor with Halcion, migraine medicines in any form, Orap, oral Versed, Xanax, or the herb St. John’s wort. Do not use Mevacor, Vitorin, or Zocor cholesterol-lowering meds; suggested alternatives are Lipitor, Lescol, Crestor and Pravachol, but liver enzymes should be checked regularly, as they can increase risk for liver toxicity with Rescriptor. Rescriptor needs stomach acid in order to be absorbed correctly.

Over-the-counter antacids, like Tums or Maalox, decrease absorption of Rescriptor, so take it one hour apart from these remedies. Other acid-reducing drugs (like Zantac, Tagamet, and Prilosec) may also reduce absorption of Rescriptor—try not to take them together for long periods of time. People with low stomach acid should take Rescriptor with acidic beverages (orange or cranberry juice, etc.) to increase acidity. Certain amphetamines and antiarrhythmic drugs should not be used with Rescriptor. Rescriptor should be used with caution with Procardia or Adalat (nifedipine), Norvasc (amlodipine), Plendil (felodipine), quinidine, and Coumadin—inform

your health care provider if you have a history of heart or blood pressure problems. Dose adjustment may be needed when taken with the antibiotic Biaxin, especially with decreased kidney function. Use caution with anti-convulsants Tegretol, phenobarbital, and Dilantin.

Mycobutin and rifampin (used to treat tuberculosis), decrease Rescriptor levels and, along with Priftin, are not recommended. Rescriptor increases levels of protease inhibitors (PIs) Crixivan, Lexiva, Invirase, Kaletra, Norvir, and Viracept, as well as immunosuppressants (including transplant drugs), birth control pills (ethinyl estradiol), and methadone, so caution is advised if using together (although boosting the PIs is now virtually Rescriptor’s only use). May increase levels of Selzentry. Cialis, Levitra, and Viagra levels are increased by Rescriptor; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Also, increased levels of Desyrel can occur with Rescriptor and therefore should be used with caution. Increased levels of the inhaled and nasal sprays that contain fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Rescriptor which can result in Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes), and therefore should not be used unless no other options are available.

More information

This drug is seldom used except in unusual situations by some people who cannot tolerate Norvir (ritonavir) and are successfully using Rescriptor instead to boost their PI. The ability to boost PI blood levels makes it unique among the NNRTIs. However, newer drugs make this use nearly obsolete as well. One doctor even reported being unable to find a supply of it for one of his patients. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Rescriptor (delavirdine) is rarely used today. It was administered three times a day and was not extensively studied. When it was, it always seemed to be outperformed by its competitors. There used to be a small smattering of people who had mutations that caused cross-resistance to all NNRTIs except delavirdine, but the approval of etravirine (Intelence) made that irrelevant.

The first attempt at an NNRTI, Rescriptor was plagued by dosing, interaction, resistance, and side effect challenges that ultimately made it not worth the effort. It does boost PI levels and has remained (barely) alive to be used as an alternative to ritonavir-boosting, but that is likely to change with other options now available.

—Dawn Averitt

—Joel Gallant, MD, MPH

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March+April 2014 | positivelyaware.com/rescriptor

Sustiva efavirenz, or EFV

NNRTI: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity

Central nervous system (CNS) or psychiatric symptoms (dizziness, insomnia, impaired concentration, abnormal dreams and hallucinations, depression, suicidal thoughts or actions, aggression, paranoid/manic reactions), usually diminishing within four weeks. Bedtime dosing may help reduce symptoms. Other side effects may include rash, nausea, vomiting, diarrhea, and fever. Rash in children is more common and more severe. May raise levels of triglycerides and cholesterol. May lead to false positive urine tests for marijuana; a confirmatory test is available.

Women should not become pregnant while on Sustiva or for 12 weeks after discontinuation, because of the risk of birth defects. However, the birth defect risk is limited to the first six weeks of pregnancy and the recommendation is that women in their first trimester continue taking Sustiva as long as their viral load remains undetectable.

Close monitoring for increased liver enzyme levels is recommended initially with regular check-ups for people with hepatitis B/C or liver disease. Use with caution when mild liver impairment exists; not recommended with moderate or severe liver impairment. Check page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking.

Do not take with Atripla, Complera, Edurant, Intelence, Rescriptor, or Viramune, since Sustiva is in these drugs or they have equivalent medication. Do not take avanafil, Gingko biloba, midazolam, pimozide, rifapentine, St. John’s wort, triazolam, or Victrelis. Sustiva may affect warfarin levels. Sustiva decreases methadone levels; dose adjustment may be necessary to avoid withdrawal.

Increase Kaletra to three tablets twice daily with food when taken with Sustiva by treatment-experienced people. Kaletra cannot be taken once daily with Sustiva.

Monitor liver enzymes closely if Sustiva and Norvir are used together. Treatment-experienced people should

not take Reyataz with Sustiva at all, but for treatmentnaïve people, Reyataz once-daily dose should be 400 mg Norvir-boosted when taken with Sustiva. Boost oncedaily Lexiva with 300 mg Norvir. Increase the Sustiva dose to 800 mg once daily with rifampin for people weighing 132 pounds (60 kg) or more. Rifabutin can be used as an alternative, but dose adjustment is needed when it is used two or three times a week. When taken with anticonvulsants carbamazepine, phenobarbital, or phenytoin, periodic monitoring of anticonvulsant and Sustiva levels should be done or alternative anti-seizure drugs considered. Effectiveness of birth control pills may be decreased; consider the use of other contraceptives.

Closer monitoring and dose adjustments may be required with azole antifungal agents posaconazole and itraconzole. The dose of voriconazole should be increased to 400 mg every 12 hours and the Sustiva dose should be decreased to 300 mg once daily. Monitor effectiveness of clarithromycin or consider alternatives. Levels of immunosuppressants should be monitored when starting or stopping Sustiva. Cardizem, Lipitor, Pravachol, Zocor, and Zoloft doses may need to be adjusted. Titrate dose of bupropion and sertraline based on clinical response.

Sustiva can decrease levels of buprenorphine—monitor for withdrawal. No dose adjustment with Sovaldi. Don’t take with Olysio. An increase in the Incivek dose is needed when taken with Sustiva.

More information

According to DHHS HIV treatment guidelines, Sustiva is preferred for NNRTI-based regimens. It has been proven to work just as well as the newer NNRTIs in people without NNRTI resistance. Avoid driving or operating heavy machinery for a few hours after dose. A sleep medication may be needed—morning grogginess is possible.

Switching the timing of your dose to daytime might help. A rare genetic trait, leading to a higher rate of side effects, occurs more in African Americans. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

a generic drug, and its lower price may force my hand.

Sustiva (efavirenz) has been a gold standard agent since its approval in 1998. To this day, it remains a recommended and widely used drug for initial therapy, most commonly taken in the form of Atripla. However, while I have many patients who have been doing well on it for many years, I rarely write a new prescription for it. Since its approval, we’ve been well aware of its neuropsychiatric side effects. We put up with them because they were usually transient and minor in comparison with the more serious side effects of other drugs we used then. Today we have drugs that don’t take “getting used to,” some of which are also included in single-tablet regimens. In addition, some people continue to have difficulty sleeping or concentrating, or get depressed, even after years on the drug. Personally, I’m happy to keep people on efavirenz if they’re doing well, but I see no reason to start someone on it. That said, efavirenz will soon be

—Joel Gallant, MD, MPH

STANDARD DOSE

One 600 mg tablet, once a day, typically at bedtime, on an empty stomach or with a light, low-fat snack.

Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. Also available in smaller 50 mg and 200 mg capsules. Approved for children 3 months and older weighing at least 7.7 pounds (3.5 kg).

For those who can’t swallow capsules, administer by capsule sprinkle method (see video on website or read label for procedure; also go to positivelyaware.com/ sustiva). Strawberry/ mint flavored solution available for children under expanded access program. manufacturer

Bristol-Myers Squibb bms.com (800) 321-1335 AWP

$862.14 / month for 600 mg tablets

Activist’s comments

Sustiva has lived a few lives—the first as a solo agent to be added to regimens and now as part of the Atripla powerhouse. Ultimately, this is a very potent drug with some real annoying quirks (like neon dreams).

The rash that a fair number of folks experience is a real nuisance, but usually transient and manageable.

Resistance is not to be toyed with—this is not three strikes, but rather one strike and you’re out (fortunately covered somewhat by a very long half life). That said, Sustiva has been an essential, successful part of long-term regimens for many people. Sustiva can cause birth defects (most likely in the first trimester), so pregnancy (planned or not) should be talked about proactively. —Dawn Averitt

March+April 2014 | positivelyaware.com/sustiva

39

Viramune XR nevirapine, or NVP

NNRTI: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity STANDARD DOSE

One 200 mg IR (immediate release) tablet once daily for two weeks, then full dose of one 400 mg tablet once daily of Viramune XR or one 200 mg IR tablet twice daily, with or without food, with no dietary restrictions.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. If you interrupt therapy for more than seven days, you will need to restart with lead-in dose above.

Pediatric 100 mg XR tablets approved for children 6 to 18 years of age. Viramune IR frequently prescribed as two 200 mg tablets once daily, although that is not FDA approved. Viramune XR once daily is approved only for adults. Dose for children 15 days or older is 150 mg/m2 once daily for 14 days, then 150 mg/m2 twice daily thereafter, not to exceed 400 mg daily.

For dialysis patients, an additional 200 mg IR is required after each dialysis. 50 mg/5 mL oral suspension also available. Generic available for immediate release formulation. manufacturer

Boehringer Ingelheim viramunexr.com (800) 274–8651 AWP

$753.52 for XR / month; $650.70 / for generic IR; $175.94 for suspension; $170.52 for generic suspension

40

Most common side effects include headache, nausea, vomiting, fever, and rash (reduced with 14-day lead-in dosing). Rarely, severe and life-threatening liver damage, sometimes fatal, has occurred. Women with CD4 T-cell counts greater than 250, including pregnant women, have the highest risk of serious liver damage, though men with more than 400 T-cells are also at risk. Viramune or Viramune XR should not be started in these groups unless the benefit outweighs the risk. The highest risk period is within the first six weeks of treatment, but patients should be monitored closely for the first 18 weeks. Severe rash, including Stevens-Johnson syndrome, while rare, can be life-threatening; notify your health care provider immediately. Seek medical attention right away if you experience blistering, mouth sores, conjunctivitis (inflammation of the eye, which if untreated may result in blindness), swelling, muscle or joint aches, fever, or general ill feeling. Do not increase dose if rash develops during dose escalation or if it is accompanied by the above conditions. During the first six weeks of therapy, avoid prednisone due to increased severity and incidence of rash. Liver enzyme levels may increase and in rare instances, hepatitis has developed. In such cases, it may be necessary to stop taking Viramune (either formulation) until liver function returns to normal.

Permanently discontinue it if abnormalities return. Check page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking. Do not take with Atripla, Complera, Edurant, Intelence, Rescriptor, Reyataz, or Sustiva. Never take St. John’s wort with Viramune.

Rifampin or Priftin (rifapentine) should not be used with Viramune; Mycobutin (rifabutin) is the recommended alternative to rifampin. Use with caution with midazolam, triazolam, fluconazole, itraconazole, voriconazole, Cordarone (amiodarone), lidocaine or disopyramide, ethosuximide, clonazepam, calcium channel blockers

(Procardia and others), immunosuppressants (including transplant drugs), and warfarin (Coumadin). Viramune decreases methadone levels; dose adjustment may be necessary to avoid withdrawal. Can reduce levels of protease inhibitors; dose adjustment may be needed if they are taken together. Kaletra should be increased to three tablets twice a day in treatment-experienced people. Use caution with anti-convulsants: carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin). Effectiveness of birth control pills may be decreased; consider the use of other contraceptives. Do not take with Olysio. Insufficient information on drug interaction with other oral hepatitis C drugs (Incivek, Victrelis, Sovaldi).

More information

The once-daily Viramune XR was FDA approved in 2011, but many providers already prescribed off-label once-daily dosing with the old formulation. The regular Viramune (IR) formulation is now available as generic nevirapine. Viramune XR is considered an alternative drug under U.S. HIV treatment guidelines, and Sustiva is the preferred NNRTI. New data last year confirms that Sustiva is better than Viramune for most patients (see reference at positivelyaware.com/viramune). Monitor liver function and signs of rash during first six months. Do not ignore yellowing of eyes or skin, as this may be a sign of a severe liver effect. Nevirapine crosses the blood-brain barrier and may be beneficial for patients at risk for neurological damage from HIV. Viramune has been shown to improve triglycerides and total cholesterol levels. When taken around the time of labor, Viramune has been effective in preventing mother-to-child transmission, but drug resistance increased when taken alone—use at least one other HIV drug to prevent resistance. Viramune may be used for babies born to HIV-positive mothers; in the first week of life, Viramune is usually given with zidovudine.

In order to prevent HIV transmission to newborns, HIVpositive mothers should not breastfeed. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Viramune (nevirapine) is still widely used throughout the world, but its popularity is fading. It was never as well studied as efavirenz (Sustiva), and when the two were compared in a head-to-head study, it was more toxic and clearly not as effective. The biggest toxicity problems occur during the first few weeks, when there’s a risk for potentially serious—even fatal—skin and liver toxicity, especially in people with higher CD4 counts. Now that we’re recommending treatment for everyone, including people with high CD4 counts, a smaller number are good nevirapine candidates. Fortunately, once you get past those first few weeks, you’re home free, and it becomes a safe and effective drug. For that reason, I don’t necessarily switch people who are doing well on nevirapine, but I never prescribe it for initial therapy.

Like Sustiva, Viramune can cause mild to severe rash, usually when first initiated. However, unlike Sustiva, Viramune does not cause the central nervous system (CNS) or psychiatric side effects and can be taken either once or twice a day depending on the formulation (XR is a 400 mg once-daily pill). Interestingly, women in the developing world have decreased mother-to-child transmission due to the drug’s effectiveness in single pill administration during labor. At the same time, it has been shown to cause liver toxicity and should not be initiated in women with a CD4 count greater than 250 or men with counts greater than 400.

The thing that intrigues me most about Viramune is the possible beneficial effect this drug has on lipids in combination with drugs like boosted PIs that may negatively impact lipids. Who knows, another non-nuke with a desirable side gig? Maybe. —Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/viramune

Aptivus tipranavir, or TPV

PI: Protease Inhibitor

Potential side effects and toxicity

Most common are mild diarrhea, nausea, vomiting, abdominal pain, and fatigue. Other side effects may include headache, fever, dry mouth, and dizziness. Rash, including sensitivity to the sun, happens in 1 out of 10 patients (commonly among children). Rash may occur with joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling skin. Women taking birth control pills may be at higher risk. Stop using Aptivus if a severe rash occurs or if rash appears with the symptoms listed above and call your medical provider immediately. Caution should be used for people with mild liver impairment; don’t use with moderate to severe liver disease. Liver function should be checked before taking this drug. If you have hepatitis B or C, it may worsen when using Aptivus. Use with caution in people who may be at risk of increased bleeding or who are taking medications that may increase the risk of bleeding. Bleeding in the brain has occurred with Aptivus, but many of the patients were also taking other drugs that may have caused or added to the bleeding risk. Use with caution in patients with allergies to sulfa drugs. Aptivus may also increase blood sugar, cholesterol, and triglycerides. See page 68 for potential drug class side effects.

Potential drug interactions

Tell your provider or pharmacist about all the medications, herbs, and supplements you are taking or thinking of taking. Do not take with alfuzosin, Revatio (sildenafil), Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), quinidine, midazolam, pimozide, triazolam, or the herb St. John’s wort. Do not use lovastatin (Mevacor, Altoprev), simvastatin (Zocor), or the co-formulations containing them (Advicor and Vytorin) for treatment of high cholesterol. Cholesterol-lowering alternatives Crestor, Lescol (fluvastatin), Lipitor (atorvastatin), and Pravachol (pravastatin) should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use with caution and only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, and more). Aptivus can lower blood levels of Intelence,

Ziagen, Videx EC, and Retrovir and they should not be combined. Take Videx EC and Aptivus two hours apart.

Aptivus should not be taken with other protease inhibitors because it greatly lowers their blood levels. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Methadone doses may need to be increased.

Buprenorphine and naloxone can lower Aptivus levels significantly; dose adjustments are not recommended. A lower dose of trazodone is recommended. Calcium channel blockers should be monitored for side effects. Avoid use of ergot derivatives (dihydroergotamine, ergonovine, ergotamine, and methylergonovine). Additional monitoring may be required when taking Coumadin (warfarin).

Seizure medicines carbamazepine, phenobarbital, or phenytoin (Dilantin) may decrease Aptivus levels; alternate seizure medications should be used if possible, and monitoring of Aptivus levels is recommended. Use caution when taking itraconazole or fluconazole. Rifampin and rifapentine should not be used; reduce the dose and frequency of rifabutin, the recommended alternative.

Use with caution with bosentan, salmeterol, immunosuppressants, and colchicine. Norvir and Aptivus capsules contain alcohol (should not be enough to trigger relapse), so be cautious with Antabuse or Flagyl. Oral solution contains vitamin E; do not take more vitamin E than found in a multivitamin. Aptivus should be taken two hours before or one hour after antacids. Prilosec dose may need to be increased. Taking with Olysio or Sovaldi is not recommended. Taking Victrelis with Aptivus can potentially reduce the effectiveness of both drugs, and combined use is not recommended.

STANDARD DOSE

Two 250 mg capsules with two 100 mg capsules of Norvir, both twice daily at the same time.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Must be taken at the same time as ritonavir (Norvir). Must take with food when using Norvir tablets; no food restrictions with Norvir capsules or solution, but preferably taken with food to improve Norvir tolerability.

Oral solution is available; both formulations available for children ages 2 years and older.

Swallow Aptivus capsules whole, do not crush or chew the capsule. manufacturer

More information

Boehringer Ingelheim

Aptivus is not as commonly used as other PIs. It is not FDA approved for treatment-naïve patients. Take with food to minimize stomach problems. Refrigerate capsules before opening, but Aptivus capsules can be stored at room temperature (up to 77˚F) if used within 60 days.

The oral solution should be stored at room temperature and used within 60 days of opening bottle. See package insert for more complete information on potential side effects and interactions.

aptivus.com (800) 542–6257

Doctor’s comments

Activist’s comments

Aptivus (tipranavir) would have been an important drug for people with PI resistance if it hadn’t been for Prezista, which also worked against PI-resistant virus, but was safer and better tolerated. Aptivus has to be boosted with a whopping 400 mg per day of ritonavir, which may be why it causes more gastrointestinal side effects and has more lipid and liver toxicity than Prezista. A small number of people have virus that’s resistant to Prezista and other PIs but susceptible to tipranavir. This unusual resistance pattern is usually a result of having previously failed therapy with Lexiva (fosamprenavir). —Joel Gallant, MD, MPH

This is a challenging PI to describe because although most of us feel that having more drugs on the market is better than fewer drugs, it’s hard to find a place for Aptivus. This drug is a true niche drug for folks who are dealing with complex resistance due to previous PI use and need this option. Aptivus requires 200 mg of ritonavir twice daily to boost it and has liver and lipid challenges that make both the toxicity and side effect profile hard to sell when there are so many other choices.

AWP

$1,500.17 / month for capsules; $500.04 for 95 mL solution

—Dawn Averitt

March+April 2014 | positivelyaware.com/aptivus

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Crixivan

indinavir sulfate (indinavir), or IDV PI: Protease Inhibitor

Potential side effects and toxicity STANDARD DOSE

Rarely used by itself (two 400 mg capsules every eight hours with no food or a low-fat snack). Almost always boosted with Norvir, both twice daily: 800 mg with 100 mg Norvir or 800 mg with 200 mg Norvir. All doses taken with food and with plenty of water to avoid kidney sludge or stones.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Avoid grapefruit juice and vitamin C (more than one gram a day). Drink plenty of non-caffeinated fluids throughout the day to help reduce the risk of kidney stones. Also available in 100 mg and 200 mg capsules. manufacturer

Merck and Co. merck.com (800) 850–3430 AWP

$548.12 / month for 180 400 mg capsules

Headache, fatigue or weakness, malaise (general ill feeling), nausea, diarrhea, stomach pain, loss of appetite, yellowing of skin/eyes, changed skin color, dry mouth/ sore throat, taste changes, painful urination, indigestion, joint pain, hives, and liver toxicity. Itchy/dry skin, ingrown toe nails, and hair loss are unique to Crixivan.

Kidney stones, which may lead to more serious problems, can also occur—if pain develops in the middle to lower stomach or the back, or if there is blood in the urine, call your health care provider immediately. An increase in bilirubin has been reported, but it is not associated with liver problems. It may sometimes cause yellowing of the skin or eyes. Crixivan has also been associated with hemolytic anemia (premature destruction of red blood cells) and it should be stopped once the anemia is diagnosed. Similar to other PIs, it may cause insulin resistance and increase in cholesterol. Body fat changes made Crixivan famous in the late 1990s and early 2000s, but it appears that these changes are more related to PI and antiretroviral therapy in general than to this particular medication. See page 68 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See the package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio (sildenafil), Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), midazolam, triazolam, rifampin, pimozide, Priftin (rifapentine), garlic supplements, or the herb St. John’s wort. Do not use lovastatin (Mevacor, Altoprev) and simvastatin (Zocor) or co-formulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol. Safer cholesterol-lowering alternatives are Crestor (rosuvastatin), Lipitor (atorvastatin), and Pravachol (pravastatin), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Not recommended in combination with Reyataz. Reduce Crixivan to 600 mg every eight hours when taken with

Doctor’s comments

At one time, Crixivan (indinavir) was the key ingredient in “the cocktail” that saved so many lives in the mid- and late-’90s. It’s rarely used now because of its complex dosing and many toxicities, including kidney stones, decreased kidney function, diabetes, lipid elevations, hair loss, dry skin, and ingrown toenails—to name a few. —Joel Gallant, MD, MPH Activist’s comments

Crixivan is one of the three PIs that ushered in the

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itraconazole (200 mg twice a day), or ketoconazole (200 mg once a day). The dose of Mycobutin (rifabutin) should be reduced to 150 mg daily or 300 mg three times a week and Crixivan dose increased to 1,000 mg every eight hours or use Norvir-boosted dose when taken together.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Additional monitoring may be required when taking Coumadin (warfarin) or calcium channel blockers. Use caution with anti-seizure medicines Tegretol, phenobarbital, and Dilantin (phenytoin).

Crixivan may decrease levels of methadone, so the dose may need to be increased, but withdrawal rarely occurs. Also, increased levels of trazodone can occur with Crixivan. Increased levels of the inhaled and nasal sprays with fluticasone (Advair, Flonase, and Flovent) and budesonide (found in Pulmicort and Rhinocort) can occur with Crixivan; use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes). Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and use a lower dose of colchicine. Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs and there are limited data to support the use of Incivek with Crixivan. Taking with Olysio is not recommended.

More information

Very rarely used. Drink at least 48 oz. of fluids daily, preferably water or clear liquids (not soda!) to decrease the chances of kidney stones. Drink more water in summer or with increased sweating. Large amounts of coffee or alcohol can increase risk of stones due to dehydration.

Stones may continue after stopping Crixivan. Store in original container and keep dry. See package insert for more complete information on potential side effects and interactions.

new era of AIDS with triple combination regimens and story after story of people getting out of their deathbeds to live again. Many of us are here because we got our hands on Crixivan in the mid-’90s, and now it has been overtaken by the PI generations (and other classes) that have come after it. Now a twice-a-day boosted drug (or complex three-times-daily restricted drug without boosting), Crixivan has more cons than pros on the balance sheet—kidney stones, metabolic challenges, and body fat redistribution to name a few.

Crixivan is largely a relic of our past. —Dawn Averitt

March+April 2014 | positivelyaware.com/crixivan

Invirase saquinavir, or SQV

PI: Protease Inhibitor

Potential side effects and toxicity

Most common are diarrhea, abdominal discomfort, vomiting, and nausea. Drug label warning states that Invirase/ Norvir may change the electrical activity of the heart, which may lead to abnormal heart rhythms called prolonged QT or PR intervals. People with underlying heart conditions, who have heart rate or rhythm problems, or low potassium or magnesium levels, are at greatest risk and should take Invirase with caution. Symptoms may include lightheadedness and fainting. A medication guide is required when Invirase is prescribed. See page 68 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Viramune and Sustiva decrease Invirase levels. Not recommended to be used with Aptivus/Norvir or Prezista. Should be used with caution and may require dose adjustment with Reyataz (additive effect on QT and PR intervals may occur). Rescriptor, Crixivan, Norvir, Viracept, and Kaletra all significantly increase Invirase concentrations.

No dosage change when taken with Kaletra, but additive effect on QT and PR intervals may occur. Invirase is contraindicated with alfuzosin, Revatio (sildenafil), Tambocor (flecainide), Rythmol (propafenone), amiodarone (Cordarone), midazolam (oral Versed), triazolam (Halcion), pimozide (Orap), quinidine, trazodone, dofetilide (Tykosyn), lidocaine (systemic), rifampin, and ergot derivatives. Colchicine levels may be increased and dose reduction is necessary. Do not use lovastatin (Mevacor, Altoprev) and simvastatin (Zocor) or co-formulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol. Cholesterol-lowering alternatives are Crestor (rosuvastatin), Lescol (fluvastatin), Lipitor (atorvastatin), and Pravachol (pravastatin), but should be used with caution and started at the lowest dose possible; you should be monitored closely for increased side effects from these medications. Invirase cannot be taken with Priftin (rifapentine) or rifampin.

Rifabutin can be used as an alternative, but its dose needs to be decreased. Methadone doses may need to be increased. Invirase increases levels of fluticasone (active component of Advair, Flonase, and Flovent) and budesonide (found in Pulmicort and Rhinocort); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes). Use calcium channel blockers with caution. Monitor digoxin levels; digoxin dose may need to be decreased. Use caution with anti-convulsants carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin), as these medications will decrease Invirase levels. Invirase may increase dapsone levels and alter Coumadin (warfarin) levels; additional monitoring may be required. Do not take with birth control pills as Invirase reduces the level of the hormone ethinyl estradiol. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Prilosec, Prevacid, or any other PPI (type of medication used to treat acid reflux or heartburn) increase Invirase levels, therefore monitor for possible side effects from Invirase if taken together. Use with caution with bosentan, salmeterol, and immunosuppressants (including transplant drugs). Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs.

Refer to the package insert for the complete guide to drug interactions.

STANDARD DOSE

Two 500 mg film-coated tablets with 100 mg Norvir two times a day with food, or within two hours of a meal for patients over 16 years old. Must be taken with Norvir (ritonavir). 200 mg hard gel capsules available.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. manufacturer

Genentech genentech.com (800) 626-3553 AWP

$1,177.58 / month for 500 mg tablets

More information

Rarely used, Invirase has efficacy similar to Kaletra with less hyperlipidemia (elevated cholesterol and triglycerides). Invirase/Norvir was downgraded from “alternative choice” to the list of “regimens that are acceptable but should be used with caution” in the U.S. HIV treatment guidelines for initial HIV therapy. Invirase must be taken with food and always with Norvir. Invirase was the first PI to lose its patent (May 2011), however there is no generic available yet. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Invirase (saquinavir) has a long and confusing history. The first approved PI, it was poorly absorbed in its original hard-gel formulation, Invirase. Then came soft-gel Fortovase, which achieved better drug levels. But ritonavir boosting revived Invirase, and Fortovase disappeared. Now, when saquinavir is used at all, it’s boosted by ritonavir. However, other PIs, namely Reyataz and Prezista, are at least as effective with lower pill burdens and once-daily dosing.

In the story of PIs, first there was Invirase. Poor absorption and a suboptimal formulation gave it a rocky start, but it came back to life as an alternate once boosting with ritonavir came on the scene.

Ultimately, Invirase shares the more common PI resistance profile and is used very rarely these days.

—Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/invirase

43

Kaletra

lopinavir / ritonavir, or LPV / r PI: Protease Inhibitor

Potential side effects and toxicity STANDARD DOSE

Four tablets (200 mg lopinavir / 50 mg ritonavir) once a day for people with less than three lopinavir resistance-related mutations; or two 200 / 50 mg tablets twice daily. Do not use once daily if taken with Sustiva or Viramune, or anticonvulsants. Three tablets twice a day may be considered for treatment-experienced people, pregnant women during the second and third trimesters, or those taking it in combination with Sustiva or Viramune.

100 mg lopinavir / 25 mg ritonavir tablets are also available.

Take missed doses as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. manufacturer

AbbVie kaletra.com (800) 222–6885 AWP

$977.22 / month for tablets; $488.60 for 160 mL oral solution

Diarrhea is the most common and can be severe, but generally less severe with tablets than liquid. It is also associated with high incidence of elevated cholesterol and triglycerides, as well as insulin resistance. Rash, nausea, vomiting, stomach pain, headache, muscle weakness, lipodystrophy, and elevated liver enzymes (a sign of liver damage—may be more common in people with hepatitis B or C). See page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking, prescribed or not. Do not take with alfuzosin, Revatio (sildenafil), Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), midazolam (oral Versed), rifampin, pimozide, Priftin (rifapentine), triazolam, garlic supplements, or the herb St. John’s wort. Do not use lovastatin and simvastatin or co-formulations containing these drugs (Advicor and Vytorin). Alternatives are Crestor, Lescol, Lipitor, and Pravachol, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Oral solution contains alcohol, so do not use with Antabuse or Flagyl. Use calcium channel blockers with caution. Dosage of methadone may need to be increased.

Current U.S. HIV treatment guidelines state the Kaletra dose should total 500 mg lopinavir and 125 mg ritonavir twice daily when used with Sustiva or Viramune.

Not recommended to be taken with Lexiva. Kaletra may lower levels of AZT and Ziagen. Videx and Kaletra can be taken together without food. If Kaletra is taken with food, Videx should be taken an hour before or two hours after Kaletra. If taking Kaletra with Viread (tenofovir) or other combinations containing tenofovir (Atripla, Complera, Stribild, and Truvada), monitor for side effects from tenofovir. Rifabutin dose should be reduced to 150 mg every other day (or 150 mg three times per week) when used with Kaletra. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Mepron levels may be reduced with Kaletra.

Avoid Sporanox or Nizoral doses greater than 200 mg per day with Kaletra. Monitor for side effects when taken

with Noxafil. Decreases voriconazole levels. People with kidney impairment may require lower clarithromycin doses with Kaletra. Monitor blood levels of immunosuppressants because levels may increase. Kaletra may alter warfarin levels; additional monitoring may be required.

Steroids, especially Decadron, may decrease Kaletra levels. Kaletra increases levels of steroids, particularly fluticasone (found in Advair, Flonase, and Flovent). Monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, and more) as well as for signs of liver inflammation (elevated liver enzymes, yellowing of the eyes or skin, etc.) if you have a history of hepatitis B infection. Kaletra increases levels of trazodone. Use caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin, as they may lower levels of Kaletra. Bupropion levels are lowered; titrate dose based on clinical response. Doses of certain ED drugs should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.

Use with caution with bosentan, salmeterol, and immunosuppressants, and use lower dose of colchicine. Kaletra can decrease the effects of Malarone. Taking with Olysio is not recommended. Incivek or Victrelis along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

According to U.S. treatment guidelines, the need for 200 mg a day of Norvir (contained in Kaletra) and the higher rate of gastrointestinal side effects compared to other PIs using 100 mg Norvir, make Kaletra an alternative (instead of “preferred”) drug for treatment-naïve people. It is on the preferred list for pregnancy and pediatrics along with boosted Reyataz, but data from 2012 adds to concerns about a link to premature births with Kaletra and other Norvir-boosted PIs (go to reference at positivelyaware. com/kaletra). Four tablets once daily can increase side effects, especially diarrhea. Taking with food and antidiarrheal medicine helps lessen diarrhea. Kaletra should not be taken once a day by children under 18. Solution cannot be given to premature babies until 14 days after their due date because it contains propylene glycol. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Lopinavir is a PI that requires boosting and is available only in the form of Kaletra. The co-formulation is both its advantage and disadvantage: Taking combined lopinavir and ritonavir prevents you from taking one without the other, but it also means you’re stuck taking four pills and 200 mg of ritonavir a day, twice what you’d take with better-tolerated Prezista (darunavir) or Reyataz (atazanavir). Kaletra causes more gastrointestinal and lipid effects than those two drugs, which is why its use has been gradually falling off. In addition, its co-formulation advantage won’t be unique much longer, since we’re expecting darunavir/cobicistat and atazanavir/cobicistat combination pills soon.

This was the first boosted and co-formulated PI combination. Kaletra was another game changer as it formalized boosting in a simplified regimen (although the original formulation has changed) for PIs at a time when many were trying to get away from PI-based regimens. Although Kaletra causes lipid abnormalities and a number of GI side effects, it reigned over the PI market for quite a while. Today Kaletra is used less frequently, although many have been on Kaletra for more than a decade and continue to use it successfully.

It is still listed as a preferred PI for use in pregnancy.

—Dawn Averitt

—Joel Gallant, MD, MPH

44

March+April 2014 | positivelyaware.com/kaletra

Lexiva

fosamprenavir calcium (fosamprenavir), or FPV PI: Protease Inhibitor

Potential side effects and toxicity

As Lexiva contains a sulfa component, use with caution in patients with sulfa allergies. The most common side effects may include nausea, rash, diarrhea, headache, and vomiting. Rash occurred in about 19% of patients, but severe rashes were uncommon. If you experience a rash, notify your doctor. For mild or moderate rashes, your doctor may choose to continue Lexiva, with close monitoring. Patients with hepatitis B or C should be monitored closely for the possibility of elevated liver enzyme levels. Dose adjustment is recommended for people with liver impairment. Side effects and laboratory abnormalities were similar when Lexiva was taken once or twice daily, with or without Norvir. See page 68 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Not recommended to be taken with Kaletra. When taken with Sustiva, boost once-daily Lexiva with 300 mg of Norvir. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, midazolam (oral Versed), triazolam (Halcion), rifampin, Orap (pimozide), Priftin (rifampetine), or the herb St. John’s wort. Do not use lovastatin (Mevacor, Altoprev) and simvastatin (Zocor) or co-formulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol. Cholesterol-lowering alternatives are Crestor, Lescol (fluvastatin), Lipitor (atorvastatin), and Pravachol (pravastatin), but use with caution and start at the lowest dose possible; monitor closely for increased side effects from these medications.

Calcium channel blockers (Norvasc, Procardia, and others) should be used with caution and careful monitoring.

Lexiva should be taken two hours before H2 blockers (Zantac, Pepcid, and others). Lexiva can lower methadone concentrations. A dose adjustment of Mycobutin (rifabutin) will be needed when used in combination with Lexiva. Steroids, such as Decadron, can decrease levels of Lexiva. Increases levels of fluticasone (found in Advair, Breo Ellipta, Flonase, Flovent, and Veramyst), and

budesonide (found in Pulmicort and Rhinocort); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes). Trazodone concentrations may increase; a lower dose of trazodone is recommended.

Drug levels of Paxil are lowered; titrate dose based on clinical response. Use with caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin. Lexiva may alter Coumadin (warfarin) levels; additional monitoring may be required. Effectiveness of birth control pills may be decreased; consider the use of other contraception methods. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.

Use with caution with bosentan, clarithromycin (Biaxin), Cordarone, Nizoral, salmeterol, Sporanox, immunosuppressants (including transplant drugs), and colchicine (lower the colchicine dose). Use of Incivek or Victrelis along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

U.S. HIV treatment guidelines recommend against Lexiva without Norvir as an option for first-time therapy because of inferior potency and the potential for developing crossresistance to Prezista, a preferred protease inhibitor for first-time treatment. The lower dose of Norvir may cause less of an increase in cholesterol and triglycerides, but it’s uncertain. Protease inhibitor-experienced patients should take Lexiva 700 mg with Norvir 100 mg, both twice daily.

The once-daily dosing is not recommended for treatment-experienced patients for whom a PI therapy has previously failed. It is important to take Lexiva exactly as your doctor instructs, and not to change dosing without discussing it with your doctor. There may be an association between Lexiva and heart attacks, heart disease, and stroke. A liquid formula of Lexiva is available. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE

For people on a PI for the first time: two 700 mg tablets with either one or two 100 mg Norvir, both once daily; or two 700 mg tablets without Norvir, twice daily; or one 700 mg tablet with 100 mg Norvir, twice daily.

For PI-experienced patients, one 700 mg tablet Lexiva with 100 mg Norvir, twice daily.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Available for children ages four weeks and older.

For people with liver problems, the dose of Lexiva may need to be adjusted and Norvir may or may not be used depending on the degree of liver disease.

A grape/bubblegum/ peppermint-flavored oral suspension is also available. Adults must take suspension without food. Tablets can be taken with or without food, with no dietary restrictions. manufacturer

ViiV Healthcare

Doctor’s comments

Activist’s comments

Fosamprenavir (Lexiva) was a new and improved version of amprenavir, a PI that was not very popular, with capsules that looked more like giant suppositories than pills. Lexiva is unique in that it can be taken boosted or unboosted, with food or without food, and once daily or twice daily. But while the dosing flexibility is attractive, it is not widely used—not because there’s anything wrong with it, but because it has no real advantages over more extensively studied PIs with lower pill burdens.

A second try on a failed drug that frankly perhaps missed its window of opportunity, Lexiva is another PI option with mediocre results, so-so dosing options (once a day boosted or twice a day unboosted), nearly 20% rash (probably because of its sulfa component), not really great for the hepatitis B co-infected population because of liver toxicity, and nothing really unique to offer. Hard to compete with better options on one or more of these levels.

viivhealthcare.com (877) 844-8872 AWP

$1,126.69 / month for capsules; $172.62 for 225 mL suspension (50 mg/mL)

—Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/lexiva

45

Norvir ritonavir, or RTV

PI: Protease Inhibitor

Potential side effects and toxicity STANDARD DOSE

Used as a boosting agent for other PIs (increases the levels of other PIs), at smaller doses of 100 to 200 mg, taken either once or twice a day with a meal.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Do not crush or chew tablets, always swallow whole. See drug label of the other PIs. Always take Norvir at the same time as the other PI prescribed.

Approved for children ages one month and older. Capsule formulation requires refrigeration. Tablet formulation is better tolerated than the capsule and does not require refrigeration.

Liquid formulation available, but it tastes horrible. Liquid formula should not be taken by pregnant women, as it contains 43% alcohol.

Most common side effects include weakness, stomach pain, nausea, diarrhea, and vomiting; tingling/numbness around the mouth, hands, or feet; loss of appetite; taste disturbance; weight loss; headache; dizziness; pancreatitis; and alcohol intolerance. Other potential side effects are an increase in liver enzymes (AST, ALT, and GGT), hepatitis (liver inflammation), jaundice (yellowing of skin or eyes), increased muscle enzyme (CPK), and uric acid.

People with hepatitis B or C may be at increased risk for liver toxicity. See page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not, as there are many other drug interactions which are not listed here. Do not take with alfuzosin, Revatio (sildenafil), Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), midazolam, Halcion (triazolam), pimozide, Priftin, Rifadin, voriconazole, garlic supplements, or the herb St. John’s wort. Do not use lovastatin (Mevacor, Altoprev) and simvastatin (Zocor) or co-formulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol. Cholesterol-lowering alternatives are Crestor, Lescol (fluvastatin), Lipitor (atorvastatin), Livalo, and Pravachol (pravastatin), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Increases levels of fluticasone (found in Advair, Flonase, and Flovent) and budesonide (found in Pulmicort and Rhinocort); monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks, bone loss, possible high blood pressure, and sometimes diabetes). Trazodone concentrations may

manufacturer

Doctor’s comments

AbbVie

Some of you old-timers will remember a brief time in history when Norvir (ritonavir) was used at full dose (6 capsules twice a day) to treat HIV infection. I’ll spare you the gory details; let’s just say it was not a pleasant experience. Then we started prescribing it at a slightly reduced—but still high—dose along with saquinavir. That was no fun either. Now we’ve abandoned ritonavir as an antiretroviral and use it only to take advantage of its drug interactions. It interferes with the metabolism of many drugs, including other PIs, allowing them to be taken at lower doses and at less frequent intervals. For reasons that still aren’t clear, ritonavir boosting also prevents PI resistance, at least in people who don’t already have resistance to begin with. The coming availability of cobicistat, another “pharmacoenhancer,” will allow an alternative boosting agent. The main advantage of

norvir.com (800) 633-9110 AWP

$308.60 / month for 30 tablets; $1,728.24 for 240 mL solution (80 mg/mL)

46

increase; a lower dose of trazodone is recommended.

Norvir may decrease levels of methadone, which may need to be increased. Use caution with anti-convulsants such as carbamazepine, phenobarbital, and phenytoin.

Use calcium channel blockers (Norvasc, Procardia, and others) with caution. Norvir may alter Coumadin (warfarin) levels; additional monitoring may be required. Do not take Xarelto as Norvir can increase Xarelto concentrations and increase risk of bleeding. Cialis, Levitra, Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception.

Levels of the street drug ecstasy are greatly increased

by Norvir, and at least one death has been attributed to the combination. GHB is also dangerous with Norvir.

Tobacco and alcohol may lower blood levels of Norvir.

Clarithromycin levels can increase by up to 80%. Use with caution with bosentan, salmeterol, and immunosuppressants; use a lower colchicine dose. Taking with Olysio is not recommended. Use of Incivek or Victrelis with Norvir can potentially reduce the effectiveness of both drugs— combined use is not recommended.

More information

The real strength of Norvir is its use with other PIs as a boosting agent. An alternative to Norvir called cobicistat, which is in Stribild, is expected to be approved on its own in the near future (see cobicistat). Stomach side effects are reduced by taking Norvir with high-fat foods—however, some other HIV medicines should not be taken with high fat foods. You can mix liquid solution one hour before taking in ice cream, milk (especially chocolate), or pudding to hide the taste. See package insert for more complete information on potential side effects and interactions.

cobicistat over ritonavir is that it will be made available for co-formulation with darunavir and atazanavir.

—Joel Gallant, MD, MPH

Activist’s comments

Norvir is famous (or infamous) for its double role in HIV. One as a PI to fight HIV and the other as a boosting mechanism that increases the drug levels of other PIs to maximize their effectiveness. In addition to being the third of the first round triumvirate of initial PIs, Norvir has actually been far more important in its role as a booster than as a PI itself. Fraught with GI distress, formulation challenges, massive drug interactions, liver toxicity, and more, Norvir was destined to fail as a PI. However, boosting other drugs (including lopinavir) has made it an essential, if not troublesome, part of the HIV treatment success story thus far.

—Dawn Averitt

March+April 2014 | positivelyaware.com/norvir

Prezista darunavir, or DRV

PI: Protease Inhibitor

Potential side effects and toxicity

As Prezista contains a sulfa component, use with caution in patients with sulfa allergies. Most common may include diarrhea, nausea, headache, rash, vomiting, and abdominal pain. Measure liver function before starting and then monitor, with perhaps closer monitoring for those with underlying liver problems, especially during the first several months. No dose adjustment necessary with mild to moderate liver disease, but Prezista/ Norvir is not recommended for those with severe liver impairment. While very rare, severe rash (in less than 0.4% of those taking it), accompanied in some cases by fever and/or elevations of AST/ALT (liver enzymes), can be life-threatening. Seek medical attention immediately.

See page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. May decrease levels of phenytoin and phenobarbital, and increase levels of carbamazepine; levels should be monitored. Reduced dose of rifabutin is recommended. Do not use lovastatin (Mevacor, Altoprev) and simvastatin (Zocor) or coformulations containing these drugs (Advicor and Vytorin) for the treatment of high cholesterol.

Cholesterol-lowering alternatives are Crestor (rosuvastatin), Lipitor (atorvastatin) (should not exceed 20 mg a day), and Pravachol (pravastatin), but should be used with caution and started at the lowest dose possible. Monitor closely for increased side effects from these medications. Reduce clarithromycin dose in kidney impairment by 50 to 70%. The antifungal drugs such as itraconazole or ketoconazole and Prezista may increase each other’s levels, so caution must be exercised when used together (maximum dose is 200 mg a day for the antifungals). Voriconazole should not be used unless the benefits outweigh the risks. Cialis (tadalafil), Levitra

(vardenafil), and Viagra (sildenafil) levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Prezista may increase levels of calcium channel blockers (like Norvasc) and beta-blockers; clinical monitoring is recommended.

A lower dose of trazodone and desipramine may be recommended. Close monitoring of INR levels required when using Coumadin (warfarin). Increases levels of fluticasone (found in Advair, Flonase, and Flovent) and budesonide (found in Pulmicort and Rhinocort); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, hump between the shoulders, rounded face, red/purple stretch marks, bone loss, high blood pressure, and sometimes diabetes). Effectiveness of birth control pills may be decreased; consider other methods of contraception.

Use lowest dose of digoxin; monitor and titrate. No dose adjustment required with buprenorphine or methadone.

Monitoring of antidepressant response is recommended with selective serotonin reuptake inhibitors (such as paroxetine and sertraline). Use cautiously with bosentan, salmeterol, immunosuppressants, and colchicine; use lower dose of colchicine. No dose adjustment needed with Sovaldi. Taking with Olysio is not recommended.

More information

Prezista is one of two preferred PIs for initial therapy in U.S. HIV treatment guidelines. There are ongoing studies with Prezista boosted with cobicistat plus emtricitabine and the investigational TAF (a variation of tenofovir), as the first PI-based single-tablet regimen. A Prezista pill that also contains cobicistat is in the works, which would eliminate ritonavir and reduce pill burden. Prezista/ Norvir is as lipid friendly as Reyataz/Norvir and more so than Kaletra, which may make metabolic problems such as diabetes, high cholesterol, and body shape changes less likely. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Prezista (darunavir) is one of two recommended PIs, along with Reyataz. Like Reyataz, it’s generally taken with 100 mg of ritonavir once a day with food.

Cobicistat boosting will be possible soon, probably with a co-formulated tablet. Twice-daily dosing is required in treatment-experienced patients who have primary darunavir mutations, which are uncommon except in people who had previously failed regimens containing Agenerase (amprenavir—no longer manufactured) or Lexiva. Prezista is well tolerated, but can cause a rash, which requires a switch to a different drug in some cases. —Joel Gallant, MD, MPH

The most recently approved PI on the market and the most commonly prescribed one, Prezista works against many of the other PI-resistant viruses and is well tolerated even though it must be boosted. Unlike many of the older PIs, Prezista has data showing no difference in efficacy in men and women because Tibotec (now Janssen) did a large study that enrolled nearly 70% women and more than 85% people of color in the U.S. (a feat that had not been done before) called the GRACE Study. This signaled an important shift in the information required by the FDA to market anti-HIV drugs in this country. —Dawn Averitt

STANDARD DOSE

One 800 mg tablet with 100 mg Norvir once daily with food for first-time therapy and treatmentexperienced adults without Prezistarelated resistance.

One 600 mg tablet with 100 mg Norvir twice daily with food for pregnant women and those whose HIV therapy has failed in the past and who have at least one Prezistarelated resistance mutation. Prezista should never be taken without Norvir.

75 mg and 150 mg tablets available for children older than three, dose based on weight. The dose for children should never exceed the adult dose.

Take missed dose as soon as possible, but not if closer to the time of your next dose. Do not double up on your next dose. An oral suspension for children three and older and adults who can’t swallow pills is available.

See the package insert for specific dose of oral solution based on weight. As with the tablet, Prezista oral solution needs to be taken with Norvir. manufacturer

Janssen Therapeutics prezista.com (800) JANSSEN (526-7736) AWP

$1,399.25 / month for all strengths

March+April 2014 | positivelyaware.com/prezista

47

Reyataz

atazanavir sulfate (atazanavir), or ATV PI: Protease Inhibitor

Potential side effects and toxicity STANDARD DOSE

One 300 mg capsule plus 100 mg Norvir, once daily (this dose must be used if taking Viread or Truvada).

Two 200 mg capsules (without Norvir), once daily can be considered for treatment-naïve adults. If pregnant, dosing depends on stage of pregnancy and other interactions—ask your doctor.

Reyataz should not be taken without Norvir by pregnant women.

Take with food.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Swallow capsules whole—do not open or mix with anything. Take Norvir pill when you take Reyataz.

With end stage kidney or liver disease, use 300 mg/100 mg Norvir.

Reyataz should not be taken by treatmentexperienced patients on hemodialysis.

Take with Norvir for children 6 years and older. Children over age 13 weiging more than 88 pounds may take Reyataz without Norvir only if they can’t tolerate Norvir and are not on any interacting medications.

Also available in 150 mg capsules. manufacturer

Bristol-Myers Squibb reyataz.com (800) 321–1335 AWP

$1,409.39 / month for 300 mg capsules; $1,422.83 / month for 200 mg capsules

48

Dizziness, nausea, and possible jaundice (yellowing of the skin or eyes), which should be reported to your medical provider right away. Other side effects may include rash, kidney stones, gall stones, abnormal heart rhythm, and elevated liver enzymes (more common in people with hepatitis B or C). Reyataz is less likely to increase lipid levels, but higher lipid levels may be seen when taken with Norvir. See page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking. Do not use lovastatin (Mevacor, Altoprev), simvastatin (Zocor), or the co-formulations containing them (Advicor and Vytorin) for treatment of high cholesterol. Alternatives for these are Crestor, Lescol, Lipitor, and Pravachol, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Proton pump inhibitors (PPIs, like Protonix, Nexium, and Prevacid) and H2-receptor antagonists (H2RAs, like Pepcid, Zantac, and Tagamet) can stop Reyataz from being absorbed.

Treatment-experienced people should not take PPIs while on Reyataz. Treatment-naïve people can take a PPI at a low dose (such as 20 mg Prilosec OTC) 12 hours before Reyataz/Norvir. Acid reducers like Pepcid may be taken (no more than 20 mg twice a day if treatmentexperienced or 40 mg twice a day if treatment-naïve) at the same time as Reyataz/Norvir or at least 10 hours later. When taking Reyataz without Norvir, the dose can be taken at least two hours before and at least 10 hours after an acid reducer. If taking chewable antacids like Rolaids and Tums, take Reyataz two hours before or one hour after. Treatment-naïve people should take 400 mg Reyataz/Norvir (100 mg) when taking with Sustiva, but treatment-experienced people should not take Reyataz

with Sustiva at all. Viread decreases the levels of Reyataz and Reyataz increases Viread levels; monitor for adverse events. Reyataz can be taken unboosted with Epzicom if necessary. Reyataz must be taken two hours before or one hour after Videx EC (unless taking Videx EC with Viread). Bepridil, Cordarone, quinidine, and lidocaine should be used cautiously because of the risk of worsening heart rhythm. Monitoring may be required when used with warfarin. Calcium channel blockers should be monitored. Use caution when using the antifungals itraconazole or ketoconazole. Voriconazole is not recommended. Reducing dose and frequency of rifabutin to 150 mg every other day or three times a week is recommended. Reyataz increases levels of fluticasone (found in Advair, Flonase, and Flovent) and budesonide (found in Pulmicort and Rhinocort); monitor for signs of Cushing’s syndrome, including rounded face. Reyataz can be taken with birth control pills that contain no more than 30 mcg of ethinyl estradiol if taking Reyataz without Norvir and at least 35 mcg if taken with Norvir. Use caution with carbamazepine, phenobarbital, and phenytoin. ED drugs should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. A lower dose of trazodone is recommended. Use with caution with bosentan, salmeterol, and immunosuppressants, and use lower dose of colchicine. Use with Norvir when taking buprenorphine.

Monitor before sedation. Taking with Olysio is not recommended. Sovaldi taken with Reyataz may cause elevated total bilirubin. Incivek can be used with boosted Reyataz.

More information

Norvir-boosted Reyataz is one of two preferred PIs in the U.S. HIV treatment guidelines for people starting HIV therapy for the first time, and is also preferred for pregnancy. It is being studied in combination with cobicistat.

See package insert for details of potential side effects and interactions.

Doctor’s comments

Activist’s comments

Along with Prezista, Reyataz (atazanavir) is one of the two recommended PIs. It’s usually taken once a day with 100 mg of ritonavir, though a co-formulated atazanavir/cobicistat pill is expected soon. Reyataz is the only recommended PI that can be taken without boosting at all, although this approach has been studied mainly in people whose viral loads had already been suppressed on boosted atazanavir. Because of a drug interaction, boosting is required when Reyataz is taken with Truvada, but it can be taken unboosted with Epzicom. Reyataz is well tolerated, but it causes a harmless elevation of bilirubin that can sometimes result in visible jaundice (yellowing of skin and eyes).

It can also cause kidney stones, kidney disease, and gallstones. It should be taken with food, and requires stomach acid for absorption. Drugs used to treat heartburn or ulcers, such as antacids, H2 blockers, or proton pump inhibitors, interfere with absorption.

While it’s possible to space out the dosing to avoid that problem, it’s generally easier just to pick a different PI.

Reyataz is often thought of as the kinder, friendlier, more flexible PI. It does not have the lipid issues that other PIs have, it can be taken boosted or unboosted, it has a different resistance profile, and it is well tolerated. It is also a very potent compound but doesn’t get absorbed well enough (perhaps even boosted) to realize its full potency in the body. On the flip side, Reyataz has a number of drug interaction issues and dose modifications depending on the other drugs you combine it with so make sure you ask about anything else you are taking specifically (especially when boosted—which applies to all boosted regimens). Most notably, antacids and proton pump inhibitors interfere with the acid the drug needs to be absorbed, so there are specific instructions on what can be used and when.

—Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/reyataz

Viracept nelfinavir, or NFV

PI: Protease Inhibitor

Potential side effects and toxicity

Most common include diarrhea, stomach discomfort, nausea, gas, weakness, and rash. See page 68 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Viracept increases levels of Invirase and Crixivan, so dose adjustments may be needed. Do not take with alfuzosin, Revatio (sildenafil), oral midazolam (Versed), Cordarone (amiodarone), dihydroergotamine (or ergotamine derivatives) triazolam (Halcion), rifampin, pimozide, Priftin (rifapetine), Prilosec OTC (omeprazole), garlic supplements, or the herb St. John’s wort. Do not use lovastatin (Mevacor, Altoprev), simvastatin (Zocor), or the co-formulations containing them (Advicor and Vytorin) for treatment of high cholesterol. Alternative cholesterol-lowering agents are Crestor (rosuvastatin), Lescol (fluvastatin), Lipitor (atorvastatin), Livalo (pitavastatin) and Pravachol (pravastatin), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Viracept may decrease levels of methadone, which may need to be increased, but withdrawal rarely occurs. Use calcium channel blockers with caution. Blood levels of Viracept are reduced by rifampin and may be reduced by carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin), so it is important to inform your doctor if you are taking any of these medications. Mycobutin (rifabutin) dose must be decreased when used with Viracept. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis per 72 hours or 2.5 mg Levitra per 24 hours, or 25 mg Viagra per 48 hours. Avanafil is not recommended for use with Viracept. Viracept increases the risk of side effects of inhaled or intranasal fluticasone (Advair, Flonase, Flovent) and budesonide (Pulmicort, Rhinocort); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, hump between the shoulders, rounded face, red/purple stretch marks, bone loss, high blood

More information

Rarely used, Viracept is the only protease inhibitor that is never used with Norvir. Diarrhea is very common with this medication. Do not leave the pharmacy without anti-diarrhea meds such as loperamide (Immodium) or calcium products, such as Tums or Oscal. For example, taking a 500 mg calcium supplement with each Viracept dose helps to decrease diarrhea within 2–3 days. If diarrhea does not decrease, you might then try Solgar oat bran tablets, psyllium husk fiber bars, or pancreatic enzymes (all with meals). Be sure to get instructions from your provider or pharmacist on how to take these medications or supplements safely. As an extra precaution, take a change of clothes with you every day for the first several weeks—stick it out, talk with your provider; most often, symptoms improve after two or three weeks.

Crofelemer (Fulyzaq; see page 64) is a prescription drug that may help people with long-term or ongoing diarrhea from antiretroviral medications including Viracept.

People using Viracept can crush or dissolve tablets in a small amount of water. Mixing Viracept with acidic food or juice (e.g., orange/apple juice or apple sauce) is not recommended, due to resulting bitter taste. To get the full benefit of Viracept by increasing its level in the body, it must be taken with a meal. No longer a preferred PI in pregnancy, Viracept is still okay to use if the preferred and alternative PIs (Kaletra, Prezista, and Reyataz) are not an option. It has been used extensively in pregnancy in the past, and it is well tolerated. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

In its heyday, Viracept (nelfinavir) had two claims to fame. It was better tolerated than its competitors—which tells you something about those drugs, since it caused a lot of diarrhea. It also didn’t cause cross-resistance to other PIs—except when it did. There’s no reason to use Viracept today.

Yet another PI of a bygone era. Viracept held a muchbeloved spot until we figured out it didn’t really work that well or for very long. Because it had fewer toxicities than the first three PIs, Viracept was used early on by cutting edge docs trying to find combination regimens to use successfully in pregnancy. Viracept has been replaced by the newer next generation PIs over the last several years. —Dawn Averitt

—Joel Gallant, MD, MPH

pressure, and sometimes diabetes). Viracept should not be used with inhaled salmeterol (Advair, Serevent) due to the increased risk of cardiovascular events caused by salmeterol. Effectiveness of birth control pills may be decreased; consider the use of other methods of contraception. Use with caution with bosentan (Tracleer), immunosuppressants (including transplant drugs), trazodone (lower trazodone dose) and colchicine (lower colchicine dose). Hepatitis C protease inhibitors, Incivek (telaprevir), Olysio (simeprevir), and Victrelis (boceprevir), should not be used with Viracept.

March+April 2014 | positivelyaware.com/viracept

STANDARD DOSE

1,250 mg taken as either two 625 mg tablets or five 250 mg tablets twice daily with food.

Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$1,093.75 / month for 250 mg and 625 mg tablets

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Isentress raltegravir, or RAL

INSTI: integrase strand transfer inhibitor (INTEGRASE INHIBITOR)

Potential side effects and toxicity STANDARD DOSE

One 400 mg filmcoated tablet twice a day, with or without food, with no dietary restrictions. Can be taken by children two years or older. Dosing is based on weight for children ages 2–11 years.

Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Pediatric formulation available as an oral suspension for ages four months and up weighing at least seven pounds and in the form of bananaorange flavored 25 mg and 100 mg scored chewable tablets (which can also be swallowed), taken with or without food. The chewable tablets are not bioequivalent to the film-coated tablets; therefore, do not substitute chewable tablets for film-coated tablets. manufacturer

Merck and Co. isentress.com (800) 622–4477 AWP

$1,352.05 / month

Very tolerable and infrequent side effects. Those reported included diarrhea, insomnia, nausea, headache, and fatigue. The side effect profile in children is comparable to adults. Rarely seen are abdominal pain, vomiting, weakness, dizziness, mild to moderate rash, anxiety, anemia (lower red blood cells), neutropenia (lower white blood cells) and lipodystrophy. May cause elevated levels of creatine kinase (a muscle enzyme). Contact your health care provider if you experience dark or tea colored urine, or if you experience unexplained muscle pain, tenderness, or weakness. Increases in ALT, AST, and total bilirubin (signs of liver toxicity) can be seen in around 8% of people taking Isentress, especially those co-infected with hepatitis B or C. Although very rarely seen, side effects can include severe and potentially fatal skin and hypersensitivity (allergic) reactions, such as Stevens-Johnson Syndrome, and cerebellar ataxia (sudden, uncoordinated movement due to disease or injury of the brain). Seek medical attention and immediately stop taking Isentress and your other HIV medications if you develop a rash associated with any of the following symptoms: fever, general ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, swelling of the eyes, lips, mouth, or face, difficulty breathing, and/ or signs and symptoms of liver problems (such as yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on the right side below the ribs). Chewable tablets contain phenylalanine, which can be harmful to patients with phenylketonuria. If you have severe liver injury or impairment, your dose may need to be adjusted by your provider. See page 69 for potential drug class side effects.

Potential drug interactions

Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Alert your provider or pharmacist to any history of rhabdomyolysis, myopathy or increased creatine kinase. Like Isentress, some medications, such as statins, fenofibrate, gemfibrozil or zidovudine, have been known to cause these conditions and should be used cautiously with Isentress. Reyataz and Reyataz/Norvir increase blood levels of Isentress, but no dose adjustment

is recommended. Use caution with rifampin—increase dose of Isentress to 800 mg twice a day. Remember to decrease the Isentress dose back to 400 mg twice a day when you finish taking rifampin. There are no data on dosing of the chewable tablets with rifampin. There is no need to increase the Isentress dose with rifabutin.

Avoid Gaviscon and other antacids containing aluminum or magnesium. Tums (calcium carbonate) can be used.

Prilosec can increase concentrations of Isentress, but no dose adjustment is recommended. There is no interaction with methadone. Isentress can be used with Incivek, Olysio, Sovaldi, or Victrelis.

More information

Data illustrate that advanced patients are having good results and almost no side effects. Previously, Isentress was the preferred INSTI under the HIV treatment guidelines of the DHHS, but the guidelines changed late last year, stating that all three INSTIs on the market have been shown to be non-inferior to the preferred regimens and are now themselves preferred regimens. Long-term Isentress data show effectiveness with great tolerability in both first-time therapy and in treatment-experienced people. When taken with Truvada, it was found to be superior to and more tolerable than Atripla. The combo is a potential option for those whose virus has developed drug resistance to the NNRTIs. DHHS guidelines note drawbacks with Isentress: twice-a-day dosing and a lower barrier to drug resistance than boosted PIs. Greater tolerability may help overcome those issues and result in greater adherence. Adherence is important because of the drug’s short half-life and its low genetic barrier to drug resistance (meaning that it may only take very few missed doses for this medication to stop working). It is important that all patients taking medication to treat HIV are at least 95% adherent. The guidelines state that before prescribing Isentress, providers may want to order a resistance test that can measure INSTI resistance (standard tests cannot). If resistance to Isentress develops, elvitegravir (part of Stribild) will likely not work. However, Tivicay (dolutegravir), part of the upcoming single-tablet regimen 572-Trii, may still be effective. See package insert for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

Isentress (raltegravir) was the first approved INSTI, and when combined with other active drugs, it was a lifesaver for people who had multi-drug resistance from years of prior therapy. It’s a safe, well tolerated drug with few drug interactions, and does not require boosting. The main disadvantages, compared to the other INSTIs, are the need for twicedaily dosing and the lack of a co-formulation. A once-daily version of Isentress is now being studied.

The first integrase inhibitor to become available, Isentress made a huge difference in the lives of many people for whom a new regimen was impossible to construct out of the existing classes of drugs. Although some say that Isentress is limited by twice-daily dosing, there are many people for whom a well tolerated and efficacious treatment that must be taken twice a day is no problem at all. It is important to support a switch to Isentress with at least one other (and preferably two) drugs you are susceptible (not resistant) to.

—Joel Gallant, MD, MPH

—Dawn Averitt

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March+April 2014 | positivelyaware.com/isentress

Tivicay dolutegravir, or DTG

INSTI: integrase strand transfer inhibitor (INTEGRASE INHIBITOR)

Potential side effects and toxicity

The most common moderate to severe side effects in clinical studies were insomnia (3%) and headache (2%).

Mild insomnia was seen in 7% of participants in one study.

Rarely (in less than 1%), hypersensitivity (an allergy-like reaction) may occur. Stop taking Tivicay if signs or symptoms of hypersensitivity occur (including but not limited to severe rash or rash with: a fever, feeling ill, fatigue, muscle or joint aches, blisters or skin peeling, blisters or sores in the mouth, redness or swelling of the eyes, facial swelling, liver inflammation, angioedema (swelling under the skin), and difficulty breathing. Associated with a small increase in creatinine (a marker of kidney function; this has been a laboratory increase not found to be a sign of kidney toxicity). Liver enzymes should be monitored in people with hepatitis B or C. Stop taking Tivicay if you experience signs of liver problems (yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale-colored bowel movements, nausea or vomiting, loss of appetite, and pain, aching, or tenderness on the right side below the ribs). See page 69 for potential drug class side effects.

Potential drug interactions

Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with the anti-arrhythmic dofetilide (Tikosyn), due to the potential for serious or life-threatening reaction. Reyataz increases Tivicay levels while Prezista and rifabutin have been shown to decrease them, but no dosage adjustment is needed.

Intelence decreases Tivicay levels by 88%. This interaction must be counteracted by the addition of Kaletra, ritonavir-boosted Prezista, or boosted Reyataz. Tivicay should be taken two hours before or six hours after taking laxatives or antacids containing aluminum, magnesium (such as Maalox), or calcium, the ulcer medication sucralfate (Carafate), oral iron or calcium supplements, or buffered medications. When taken together, these medications can reduce the absorption of Tivicay. Acid reducers (such as omeprazole) and proton pump inhibitors are okay to use as no change in Tivicay levels was seen. Avoid taking with oxcarbazepine, phenytoin, phenobarbital,

carbamazepine, and St. John’s wort. Closely monitor with metformin; metformin dose may need to be adjusted.

Use alternatives to rifampin, efavirenz, Aptivus/Norvir, and Lexiva/Norvir when possible in people with INSTI experience or with certain INSTI drug resistance patterns or clinically suspected resistance. Tivicay can be taken with oral contraceptives as it is expected to have minimal effect on their levels.

More information

Tivicay was approved by the FDA in August 2013.

According to DHHS HIV treatment guidelines, all three INSTIs on the market have been shown to be non-inferior to preferred guideline regimens and are now themselves preferred regimens. The guidelines noted that while Tivicay has been found non-inferior to Isentress and superior to Norvir-boosted Prezista and regimens containing efavirenz (such as Atripla), “largely because of more discontinuations for adverse events or other reasons in the comparator arms,” it also has the shortest follow-up data and post-marketing (real world) experience. Tivicay is a second-generation INSTI, meaning that it can work in many individuals whose virus has developed resistance to other drugs in its class, like Isentress and elvitegravir (in Stribild), but it needs to be dosed twice daily in these people. This could have financial impact. It is about the size of an aspirin. Based on current data, Tivicay appears to be an exciting addition to current antiretrovirals. It will likely be co-formulated as one pill once daily with Epzicom for treatment-naïve patients (see 572-Trii, page 58). It has fewer drug interactions than Stribild and appears to be well tolerated. In laboratory studies, Tivicay has been shown to have a high barrier to drug resistance. In clinical studies to date, drug resistance has not been seen in treatment-naïve people (those on HIV therapy for the first time) whose therapy with Tivicay has stopped working; this potentially gives them more options for future treatment, but there is no switch data to date—time will tell.

See more study information on this at positivelyaware. com/tivicay. A pediatric sprinkle formulation of Tivicay is being studied. Data on its use in children ages 6 to 12 are expected this year. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE

One 50 mg tablet once daily for people on HIV therapy for the first time or treatmentexperienced people with no previous INSTI use. One 50 mg tablet twice daily when also taking efavirenz (Sustiva), Lexiva/ Norvir, Aptivus/ Norvir, or rifampin, or in people with INSTI (Isentress or elvitegravir) drug resistance or suspected resistance.

Tivicay is approved for patients 12 years and older weighing at least 88 pounds. It may be taken with or without food.

Take missed dose as soon as possible, unless it is within 4 hours of your next dose, then skip the missed dose.

Do not double up on your next dose. Not recommended for people with severe liver impairment. Use with caution in people with severe kidney impairment who have INSTI drug resistance or suspected resistance because Tivicay levels may be decreased. manufacturer

ViiV Healthcare Doctor’s comments

Activist’s comments

Tivicay (dolutegravir) is the newest INSTI, and it looks like a winner. It’s taken as a single tablet once a day without the need for boosting, is well tolerated, and may be less prone to resistance than the other two INSTIs. At double the usual dose, it can be active against some INSTI-resistant virus, though if you have enough INSTI mutations—and the right ones—you can have cross-resistance to Tivicay as well. We expect approval of a single-tablet regimen combining dolutegravir with abacavir and lamivudine soon (see 572-Trii).

Tivicay was approved in August 2013 and is considered a second-generation integrase inhibitor because it appears to work against virus that’s resistant to Isentress. Tivicay appears to be well tolerated and does not need to be boosted. It is currently being dosed once a day for treatment-naïve patients and twice a day for treatment-experienced patients who need to construct a new, viable regimen.

viivhealthcare.com; tivicay.com (877) 844-8872 AWP

$1,479.59 / month

—Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/tivicay

51

elvitegravir Investigational drug at press time; photo unavailable.

elvitegravir, or EVG

INSTI: integrase strand transfer inhibitor (INTEGRASE INHIBITOR)

Potential side effects and toxicity STANDARD DOSE

85 mg or 150 mg once a day boosted with 100 mg Norvir when taken with Reyataz or Prezista, respectively, used in research. Take with food. (Not yet approved at press time.)

Most common side effects are nausea, diarrhea, headache, and fatigue. Laboratory abnormalities indicating potential liver damage were lower with elvitegravir than with raltegravir (Isentress). Liver enzymes (ALT, AST, and GGT) can also be elevated as elvitegravir and cobicistat are processed through the liver (but the incidence is not higher than with PIs or NNRTIs). Available data are limited due to the recent approval of this medication.

See page 69 for potential drug class side effects.

Potential drug interactions

Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. manufacturer

Gilead Sciences, Inc. gilead.com (800) GILEAD-5 (445–3235) AWP

TBD; drug not yet approved as a stand-alone drug at press time. Currently available only as a component of the single-tablet regimen Stribild

52

See package insert for most complete list of interactions.

Elvitegravir is metabolized (broken down) primarily by the liver enzyme CYP450-3A (known as the P450 pathway) and any medications that affect this enzyme may affect the levels of elvitegravir. It is co-formulated with emtricitabine, tenofovir, and cobicistat in the combination tablet Stribild. Multiple drug interactions are possible with cobicistat, therefore, you should tell your provider or

pharmacist about all medications, herbal products, and supplements you are taking or thinking of taking, prescribed or not.

More information

According to Department of Health and Human Services HIV treatment guidelines, all three INSTIs on the market have been shown to be non-inferior to preferred regimens and are now themselves preferred regimens. As part of Stribild, elvitegravir was compared with Atripla and boosted Reyataz plus Truvada in patients who had never had HIV treatment. In both studies, it was shown to be non-inferior (no better, no worse) to the other regimen.

Other data showed it to be as effective as Isentress; see more information at positivelyaware.com/elvitegravir.

Providers may want to order a resistance test that can measure INSTI resistance (standard tests cannot) prior to initiating a regimen containing elvitegravir. See package insert, when available, for more complete information on potential side effects and interactions.

Doctor’s comments

Activist’s comments

At the moment, elvitegravir is available only in a single-tablet co-formulation combined with tenofovir, emtricitabine, and the pharmacoenhancer (booster) cobicistat in the form of Stribild, although a stand-alone version is likely to be approved soon, which will allow it be used in other combinations.

Elvitegravir has been approved as a component of the fixed dose combination Stribild. The FDA did not approve Gilead’s first submission for elvitegravir to be a stand-alone agent, but they’ll try again.

—Dawn Averitt

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/elvitegarivir

Fuzeon

enfuvirtide, T-20, or ENF ENTRY INHIBITOR: Fusion inhibitor

Potential side effects and toxicity

The most common are injection site reactions (ISRs), which occur in virtually all patients. The severity of reaction is variable, and for most is mild to moderate.

Symptoms could include itching, swelling, redness, pain or tenderness, and hardened skin or bumps. Bumps, termed “nodules,” seem to occur more frequently and severely in areas of high muscle mass (most notably the center of the stomach—the abs—and the thighs).

They will hurt with movement. Other side effects may include diarrhea, nausea, and fatigue, but these are more likely due to the other HIV medications taken along with Fuzeon. Hypersensitivity (allergic-like) reactions are possible. Results of a post-marketing observational study were added to Fuzeon’s drug label showing a higher incidence of pneumonia in people taking Fuzeon. Risk factors for pneumonia included a low CD4+ T-cell count or high viral load when starting therapy, intravenous drug use, smoking, and a previous history of lung disease. It is unclear if this was related to the use of Fuzeon, so report cough, fever, or trouble breathing to your health care provider immediately. See page 69 for potential drug class side effects.

Potential drug interactions

To date, no interactions that are clinically significant have been found.

More information

With other powerful, newer drugs on the market, the twice-daily injectable Fuzeon is truly a medicine of last resort. Fuzeon is intended for treatment-experienced patients. Store kit at room temperature. Preparing and

Doctor’s comments

Fuzeon (enfuvirtide, T20) blocks the fusion of the viral membrane with the CD4 cell membrane. It served its purpose for a short time in the mid-2000s, when so many people had highly resistant virus and were desperate for treatment options. But it was an expensive, difficult drug, requiring subcutaneous injections twice a day and often leaving people with painful bumps at injection sites that could last for days. Few people need Fuzeon anymore because of the availability of integrase inhibitors, a CCR5 antagonist, and secondgeneration PIs and NNRTs. I could imagine a hypothetical patient who would still need Fuzeon: someone with dual/mixed-tropic virus, resistance to all protease inhibitors, NNRTIs, and NRTIs, and susceptibility only

injecting Fuzeon can be complicated, so ask your health care provider to teach you how to do it. First, the drug needs to be dissolved with sterile water (provided in the kit), which may take up to 45 minutes. Never shake the vial with the Fuzeon, it will foam. Instead, roll it gently in your hands. To save time, you can prepare the two daily doses at the same time. You should store your second dose in the refrigerator, but it must be used within 24 hours of mixing it (allow it to warm to room temperature before using). Before injecting, it is important to make sure that the Fuzeon powder is completely dissolved.

To minimize injection site reactions, inject where you can pinch an inch (upper arm, stomach, or thigh). If not, then be sure to use half the length of the needle. Inject slowly and apply a gentle massage after injection. Try using vibrating devices after injections. Using insulin syringes to inject instead of the ones in the kit may help decrease the injection site reactions. Taking a shower before injecting helps warm and soften the skin and may also help reduce injection site reactions. Some patients use Arnica cream to decrease the inflammation. Follow proper hygiene instructions to avoid infection. ISR may worsen when injection is repeated in the same spot or given deeper than intended, for example, into the muscle.

Always rotate injection sites frequently. Never inject into moles, scars, bruises, nodules, or the navel. Fuzeon can be taken at the same time as other anti-HIV drugs. Fuzeon is the only anti-HIV compound on the market called a fusion inhibitor. Fusion inhibitors block fusion of HIV with a cell before the virus enters the cell and begins its replication process. Fusion inhibitors are a type of entry inhibitor.

See package insert for more complete information on potential side effects and interactions.

to INSTIs. Such a person would need a fully active drug to combine with an INSTI, and Fuzeon would be the only option. Fortunately, that kind of extreme resistance is quite rare. —Joel Gallant, MD, MPH Activist’s comments

STANDARD DOSE

One subcutaneous (under the skin, like insulin) injection of 90 mg (1 mL) twice daily (every 12 hours) into the upper arm, thigh, or abdomen. Take with or without food, with no dietary restrictions.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Each injection should be given in a different location from the previous one and at a site where there is no current injection site reaction from a previous dose. It is also approved for children 6 years or older. The dose for children is based on weight. manufacturer

Genentech genentech.com, fuzeon.com (877) 4–FUZEON (438–9366 AWP

$3,513.49 / month for 90 mg kit

Hard to believe that Fuzeon has been on the market for more than a decade now. When it was approved in 2003, it was groundbreaking as it introduced a new class at a time when many needed new options.

Delivered twice daily via injection coupled with a crippling cost has made this drug viable and interesting only to those in the greatest need of a new choice.

—Dawn Averitt

March+April 2014 | positivelyaware.com/fuzeon

53

Selzentry maraviroc, or MVC

ENTRY INHIBITOR: CCR5 antagonist

Potential side effects and toxicity STANDARD DOSE

150, 300, or 600 mg twice daily (available in 150 mg and 300 mg tablets). Can be taken with or without food, with no dietary restrictions. The recommended dose varies, depending on other medications being taken. Your doctor or pharmacist can determine which medications will affect Selzentry levels and recommend the appropriate dose for you.

Take a missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. Before you start Selzentry, you will need a specific blood test (a tropism assay: Trofile, Trofile DNA, or HIV-1 Coreceptor Tropism with Reflex to UDS) to determine if this medication will work for you. The manufacturer recommends the phenotypic Trofile test (or Trofile DNA for those with undetectable viral load). Results of a tropism test may take up to a month.

Genotypic tests are also available and may provide a faster and less expensive alternative. Selzentry only works for those people with CCR5tropic virus.

The most common side effects include cough, fever, cold, rash, muscle and joint pain, stomach pain, dizziness, and trouble sleeping. Other potential side effects may include allergic reactions, liver toxicity, and heart problems in those with a history of heart disease. Stop taking Selzentry and contact your doctor right away if you develop a rash, yellowing of your eyes or skin, dark urine, vomiting, or upper stomach pain. Rarely, Selzentry can cause dizziness or fainting when standing up due to low blood pressure. Selzentry should not be used in people with severe or end-stage kidney disease who are taking medications that can affect the levels of Selzentry (check with your provider). Selzentry affects immune system cells and could possibly increase the risk of infections and cancer, although this has not been observed in studies with up to five years of follow-up, and some data indicates it may be beneficial in cancer or for preventing metastasis (the spread of cancer to other parts of the body). See page 69 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Dose adjustments with other medications and anti-HIV drugs include: 150 mg twice daily if taken with medications that increase the levels of Selzentry such as protease inhibitors (except for Aptivus), Rescriptor, clarithromycin, and itraconazole; 300 mg twice daily if taken with Aptivus, Viramune, Isentress, Fuzeon, and all of the NRTIs and medications that do not affect the levels of Selzentry; and 600 mg twice daily if taken with medications that decrease the levels of Selzentry such as Sustiva, Intelence, rifampin, and some anti-convulsants

Doctor’s comments

The only approved CCR5 antagonist, Selzentry (maraviroc) blocks the binding of viral gp120 to the CCR5 co-receptor on the CD4 cell surface. It should be used only in people with R5-tropic virus: virus that can only enter the cell by binding to the CCR5 co-receptor.

Some people have virus that can get into cells by binding to the CXCR4 co-receptor (X4-tropic virus) or to both co-receptors (dual/mixed-tropic virus). To use maraviroc, you should have only R5-tropic virus, determined by a genotypic or phenotypic tropism assay. (The Trofile DNA test can determine tropism in people with undetectable viral loads.) Selzentry is a safe and well tolerated drug used primarily in

such as carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin). Dose change may be required if kidney function is less than 30 mL/min. Not recommended with rifampin (see above dosage adjustment if rifampin must be used), rifapentine, or St. John’s wort.

More information

Selzentry is now generally recommended only when anti-HIV medications from other classes cannot be used.

Complex dosing, the need for a tropism test, and competition from newer drugs have dimmed some of the initial enthusiasm for this drug. Viral tropism refers to the types of HIV that a person can have, CCR5 (R5) or CXCR4 (X4). Selzentry blocks CCR5, a receptor on the outside of a cell, and shuts down this point of entry for the virus.

Most people are infected with R5 virus, and then over time, X4 and mixed viruses may accumulate. Blocking R5 with Selzentry does not cause a shift to X4 or negatively affect disease progression or CD4 count in people whose virus can use either R5 or X4 (dual-tropic). In the MERIT clinical trial, the initial analysis suggested that Selzentry was unable to match Sustiva’s viral loads of less than 50 copies (undetectable), but a re-analysis of the data with a more sensitive tropism test showed the regimens to be comparable in achieving undetectable viral loads in treatment-naïve participants at 96 weeks, leading to FDA approval for this group. The tropism test needed is now generally paid for by public health departments, Medicare, and private insurance, though ACA insurance exchange policies may not cover it. ViiV may cover the payment for the Trofile test if someone is ADAP-eligible and insurance doesn’t cover the test. Selzentry seems to have minimal impact on lipid levels. See package insert for more complete information on potential side effects and interactions.

treatment-experienced patients. It has also been studied for initial therapy and as a component of NRTIsparing regimens, but with underwhelming results.

—Joel Gallant, MD, MPH

Activist’s comments

The first entry inhibitor to hit the market, Selzentry has struggled to find a place. The complicated diagnostic process (tropism assay) to determine if Selzentry will work combined with cost and effective options in the marketplace have made this drug a bit of a bust, although several other therapies have had slow starts only to find a place when we learned a bit more. Stay tuned.

—Dawn Averitt

manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872 AWP

$1,361.21 / month for 300 mg tablets

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Atripla

efavirenz / emtricitabine / tenofovir, or EFV / FTC / TDF STR: Single-Tablet Regimen | NNRTI and NRTIs

Potential side effects and toxicity

See the individual drugs contained in Atripla—Sustiva, Emtriva, and Viread (efavirenz, emtricitabine, and tenofovir). Atripla is well tolerated in most, but not all, individuals. Use with caution in individuals with depression or other psychiatric issues who are not under a psychiatrist’s care. Other side effects may include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. These common side effects may go away after a few weeks. Kidney function should be assessed before initiating treatment and throughout therapy as determined by a provider. Women should not become pregnant on Atripla or for 12 weeks after discontinuation, because of the slight risk of a serious birth defect (greatest in the first trimester). Dose cannot be adjusted for people with kidney problems.

Potential drug interactions

See the individual drugs contained in Atripla: Sustiva, Emtriva, and Viread. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not, as there are many other drug interactions which are not listed here. Do not take Atripla with Combivir, Complera, Edurant, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Intelence, Rescriptor, Stribild, Sustiva, Trizivir, Truvada, Viramune, Viread, or 572-Trii since these medications are already in Atripla or they have equivalent medications.

Atripla should not be taken with ergot derivatives, midazolam (oral Versed), pimozide, triazolam, voriconazole (Vfend), or St. John’s wort.

More information

Atripla was the first complete HIV treatment regimen in one pill, taken once daily. It is one of seven preferred

regimens for treatment-naïve patients in the Department of Health and Human Services (DHHS) HIV treatment guidelines. One benefit of a single tablet regimen (STR) is a decrease in the number of insurance co-pays. Sustiva (efavirenz) should not be taken during pregnancy.

However, because the birth defect risk is limited to the first six weeks of pregnancy and pregnancy is rarely recognized before six weeks, the recommendation is that women in their first trimester continue taking Sustiva as long as their viral load remains undetectable. The Sustiva in Atripla can cause a false positive for marijuana on certain drug tests. A more specific confirmatory test can be done. Most treatment-experienced people (those who’ve already been on HIV therapy) may not be able to use Atripla due to having developed drug resistance (when their medications may no longer work against the virus). Drug resistance most commonly occurs when people don’t take their HIV medicine as prescribed, but some may also be infected with a drug-resistant virus against which some of the medications in Atripla will not work. Because it is one dose once a day, it is important not to miss a dose. Be careful when stopping Atripla, so that you avoid the rapid development of HIV resistance to it—check with your doctor or pharmacist first. Use of Viread must be monitored in people with underlying kidney problems. In this co-formulation, the Viread and Emtriva dose cannot be adjusted. Therefore, Atripla should not be used in people with severe kidney problems. Check for hepatitis B before starting therapy (see Emtriva). Gilead and BMS are forever to be commended for working together to bring Atripla to market, the first collaboration of its kind. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE

One tablet (600 mg efavirenz / 200 mg emtricitabine / 300 mg tenofovir), once daily, preferably at bedtime, on an empty stomach or with a light, low-fat snack for patients 12 years and older weighing at least 88 pounds.

Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.

Do not split or crush the tablet. Dose cannot be adjusted for people with kidney problems and Atripla should not be used in people with moderate or severe kidney or liver impairment. manufacturers

Bristol-Myers Squibb bms.com (800) 321–1335 and

Doctor’s comments

Activist’s comments

Atripla was the first single-tablet, once-daily regimen.

It’s a preferred regimen in all treatment guidelines based on its outstanding efficacy, safety, tolerability, and convenience. The main disadvantages include the potential for kidney toxicity with tenofovir (see Viread) and the early side effects of efavirenz (see Sustiva). Atripla is not a good choice for people who aren’t fully committed to staying on therapy without interruption. The long half-lives of the three drugs mean that an occasional missed dose or two won’t matter, but interrupting therapy altogether can cause drug resistance, especially to efavirenz.

Atripla has taken the market by storm. After more than 25 years of cobbling together complex, often toxic, super-challenging regimens, we now had an entire regimen in one pill that we can take only once a day—at least for treatment-naïve patients. Atripla has given new life to Sustiva and sustained the ongoing reign of Truvada-based regimens—but only for a minute, because the world of fixed dose combinations is exploding with new options. —Dawn Averitt

Gilead Sciences gilead.com www.atripla.com (800) GILEAD-5 (445–3235) AWP

$2,402.04 / month

—Joel Gallant, MD, MPH

March+April 2014 | positivelyaware.com/atripla

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Complera

rilpivirine / emtricitabine / tenofovir, or RPV / FTC / TDF STR: Single-Tablet Regimen | NNRTI and NRTIs

STANDARD DOSE

One tablet (25 mg rilpivirine / 200 mg emtricitabine / 300 mg tenofovir) once daily, with a meal such as a slice of pizza; two slices of whole wheat toast with peanut butter and fresh fruit; a roast beef sandwich on a hard roll with mayo; pasta and meat sauce with salad; or tortilla with chicken, rice, and beans. Complera must be taken with a meal including some fat.

Nutritional drinks, even high-calorie protein shakes or products like Ensure, are not enough for proper absorption, and do not constitute a meal. Taken with a protein shake, Edurant levels were still half of what they are with a meal.

Take missed dose as soon as possible unless it is closer to the time of your next dose. Do not double up on your next dose. The doses in this single-tablet regimen cannot be adjusted for people with kidney function of less than 50 mL/min— therefore, it should be used with caution in individuals with kidney problems. manufacturer

Gilead Sciences, Inc. gilead.com (800) GILEAD-5 (445–3235)

Potential side effects and toxicity

More information

See the individual drugs contained in Complera—Edurant and Truvada. Moderate to severe side effects are uncommon: insomnia, headache, and depressive disorders (depression, negative thoughts, suicidal thoughts or actions) were each seen in 2% of study participants.

Complera can be difficult to take because of its food requirement and drug interactions, and so excellent adherence is critical. Moreover, the risk of virologic failure (not achieving undetectable viral load) and developing resistance and a greater number of drug resistance mutations is greater with Complera than with Atripla in people starting with viral loads greater than 100,000 copies/mL or with a CD4 count less than 200 cells/mm3. Those with a viral load of 500,000 or more in the STaR study had a greater risk of virologic failure. See positivelyaware.com/edurant for more information. Accordingly, Complera is FDA approved for people starting therapy for the first time who have viral loads of 100,000 copies/mL or less and for treatmentexperienced patients with undetectable viral loads (less than 50 copies per mL) who are switching from another regimen. In the STaR study, Complera was more tolerable than Atripla and did not have the same cholesterol elevations. Nervous system and psychiatric events were the most common side effects but higher in the Atripla group.

Concerns about switching from Atripla to Complera were eased when decreases in Complera levels were only seen in the first few weeks of a 12-week study (when Atripla levels were still high enough to be effective against HIV), and participants maintained their undetectable viral loads. All the drugs in Complera have long half-lives (time it takes a drug in the body to be reduced by half), making them a great combination. Complera pills are smaller in size than Atripla. Check for hepatitis B before starting therapy (see Emtriva). Some government programs may not pay for Complera but require that patients take its components separately. Kudos to Janssen Therapeutics, developer of Edurant, and Gilead for collaborating on Complera. See package insert for more complete information on potential side effects and drug interactions.

Potential drug interactions

Do not take this drug with Atripla, Combivir, Edurant, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Intelence, Rescriptor, Stribild, Sustiva, Trizivir, Truvada, Viramune, or Viread, since Complera contains these medications or has equivalent medication. Tell your provider or pharmacist about all medications, herbal products, and supplements you are taking or thinking of taking, prescribed or not, as there are many other drug interactions which are not listed here. Proton pump inhibitors (PPIs, stomach acid drugs like Nexium, Prevacid, Prilosec, etc.) can’t be taken with Complera. Antacids can be taken two hours before or four hours after a Complera dose. Acid reducing drugs like Pepcid, Tagamet, and Zantac, can be taken 12 hours before or four hours after a Complera dose. Do not take Complera with Tegretol (carbamazepine), oxcarbazepine, phenobarbital, or Dilantin (phenytoin); rifampin, or Priftin; or the herb St. John’s wort (other herbs have not been studied with Complera, but use caution if planning to take any herbs). Rifabutin must be taken with an extra Edurant tablet. Do not take with more than one dose of the injectable steroid dexamethasone. Use caution if used with Diflucan, Sporanox, Nizoral, Noxafil, and Vfend.

Use azithromycin when possible instead of the antibiotics clarithromycin (Biaxin), erythromycin, or Ketek, because these agents increase Edurant (rilpivirine) levels, which can increase the risk for side effects. Reduced methadone levels can be seen and while dose adjustments are not necessary, it is recommended to monitor for withdrawal. Early data shows that Complera may be taken with Incivek, Olysio, Sovaldi, and Victrelis without any dose adjustments.

Doctor’s comments

Activist’s comments

Complera is the second single-tablet regimen. A headto-head comparison of Atripla and Complera is in progress, since the original Edurant studies didn’t use the single-tablet regimen. Well-tolerated Complera is a good choice for people who have trouble with Atripla, Sustiva, or boosted PIs, but be careful about switching directly from Atripla to Complera if your viral load isn’t undetectable yet. Sustiva lowers Edurant levels, and we don’t know whether early switches are safe.

The second single-tablet regimen to hit the market has not had quite the same launch into the stratosphere as Atripla, perhaps because once someone starts a regimen they are in no hurry to change. The calmer, nicer side effect profile of Edurant may catch on once the side effect profile of the Sustiva in Atripla gets tiresome.

—Dawn Averitt

—Joel Gallant, MD, MPH

AWP

$2,463.37 / month

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Stribild

elvitegravir / cobicistat / emtricitabine / tenofovir, or EVG / COBI / FTC / TDF STR: Single-Tablet Regimen | Boosted Integrase Inhibitor and NRTIs

Potential side effects and toxicity

See the individual drugs contained in Stribild: elvitegravir, Emtriva (emtricitabine), Viread (tenofovir), and cobicistat. Note that since elvitegravir and cobicistat are newly approved drugs (as components of this combination), their long-term side effects are not known at this time. Most common are nausea, diarrhea, and headache.

Abnormal dreams and fatigue have also been seen.

Others include changes in kidney function tests (see cobicistat, page 59, for more, and reassuring, information), increases in total cholesterol, bone problems, and elevated liver function tests.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with Atripla, cobicistat, Combivir, Complera, elvitegravir, Emtriva, Epivir, EpivirHBV, Epzicom, Hepsera, Isentress, Kaletra, Norvir, 572Trii, Tivicay, Trizivir, Truvada, or Viread, since these medications are already in Stribild or it has equivalent medications. Do not take at the same time with antacids.

Separate by at least 2 hours from antacids containing aluminum, magnesium hydroxide, or calcium carbonate. Stribild is safe to take with proton pump inhibitors (Nexium, Prevacid, Prilosec) or acid reducers (Pepcid, Tagamet, Zantac). Elvitegravir can decrease blood levels of many medications. Cobicistat is expected to have many drug interactions similar to those seen with Norvir.

Do not take Stribild with Advicor, alfuzosin, Altoprev, methylergonovine, Mevacor, oral midazolam, pimozide, Revatio, rifabutin, Rifadin, rifampin, Simcor, triazolam, Uroxatral, Vytorin, Zocor, or St. John’s wort. Risks vs. benefits of using Stribild and voriconazole together should be assessed. Alternative cholesterol-lowering drugs are Crestor, Lipitor, and Pravachol, but should be used with caution and started at the lowest dose possible. Monitor closely for increased side effects from these medications, such as muscle pain. Concentrations of antidepressants such as trazodone or Prozac may be increased by Stribild, and their doses may need to

Doctor’s comments

Stribild is a good choice for initial therapy. It’s well tolerated and effective at high and low viral loads.

It’s important to know that cobicistat (COBI) reduces excretion of creatinine by the kidneys. This increases the creatinine level in the blood, which isn’t a problem except that it can give the appearance of kidney toxicity, which is detected by measurement of creatinine. This effect occurs within the first few weeks and tends to be mild, but since tenofovir can sometimes cause true kidney toxicity, it’s important to take larger or progressive creatinine elevations seriously. Other commonly used drugs, such as Tivicay (dolutegravir), ritonavir, and trimethoprimsulfamethoxazole (Bactrim, Septra), have the same effect, but to a slightly lesser degree than COBI. Because it’s a pharmacologic booster like ritonavir,

be reduced. Use with caution and therapeutic monitoring, if available, for antiarrhythmic drugs like digoxin.

Stribild increases levels of fluticasone (found in Advair, Flonase, and Flovent) and should be monitored for signs of Cushing’s syndrome (such as rounded face). Use caution with anti-convulsants such as carbamazepine, phenobarbital, and phenytoin, and calcium channel blockers.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased, consider the use of alternative other contraception methods. Use with caution with bosentan, salmeterol, and immunosuppressants like Prograf, Gengraf, Neoral, and Sandimmune. Taking with Olysio is not recommended. Use of Incivek at regular dose should be fine. Victrelis with Stribild can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

Stribild was approved by the FDA in 2012 and listed as an alternative regimen for HIV treatment-naïve people in U.S. treatment guidelines, but it is now recommended as a preferred regimen. Approval was initially based on 48-week data with 1,400 individuals showing Stribild was non-inferior (no better, no worse) at achieving undetectable viral load of less than 50 copies per mL, compared to Atripla and to Norvir-boosted Reyataz with Truvada. In October 2013, the Department of Health and Human Services (DHHS) updated recommendations on Stribild to make it one of the preferred regimens, as 96-week data from Phase 2 and 3 clinical trials and additional data through 144 weeks confirmed that Stribild remained non-inferior to Atripla and Norvir-boosted Reyataz with Truvada. Stribild should not be started in people with severe liver impairment or impaired kidney function (creatinine clearance less than 70 mL per minute). People should be checked for hepatitis B before starting therapy (see Emtriva). Insurance companies may require prior authorization. See package insert for more complete details about potential side effects and drug interactions.

STANDARD DOSE

One tablet (150 mg elvitegravir / 150 mg cobicistat / 200 mg emtricitabine / 300 mg tenofovir) once daily with food.

Take missed dose as soon as possible, unless it is closer to the time of your next dose.

Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems, therefore it should not be started in individuals with estimated creatinine clearance (CrCl) less than 70 mL/minute and should be discontinued if CrCl decreases to less than 50 mL/minute. manufacturer

Gilead Sciences, Inc. gilead.com (800) GILEAD-5 (445–3235) AWP

$2,948.70 / month

cobicistat has many drug interactions. If a drug interacts with ritonavir, it’s likely to interact with cobicistat.

—Joel Gallant, MD, MPH

Activist’s comments

The “quad” pill, as it is affectionately known in the community, has yet to conquer the universe as once predicted. An impressive combination of classes coupled with a unique boosting agent in cobicistat does offer a fresh approach to boosting regimens and sampling drug classes packaged up all neatly sort of like a TV dinner. As awesome as simple dosing regimens are, the old schooler in me still likes to know what is doing what. If something goes wrong with Stribild (or any STR for that matter), you sort of have to throw the baby out with the bathwater (and overcome the hangup that it all has to be in a single pill). —Dawn Averitt

March+April 2014 | positivelyaware.com/stribild

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572-Trii Investigational drug at press time; photo unavailable.

dolutegravir / abacavir / lamivudine, or DTG / ABC / 3TC STR: Single-Tablet Regimen | INSTI and NRTIs

Potential side effects and toxicity STANDARD DOSE

One tablet (50 mg dolutegravir / 600 mg abacavir / 300 mg lamivudine) once a day for people on HIV therapy for the first time used in research.

Twice-daily dosing in people who have viral resistance to Isentress and elvitegravir.

Take missed dose as soon as possible, unless it is closer to the time of your next dose.

Do not double up on your next dose. manufacturer

ViiV Healthcare viivhealthcare.com (877) 844-8872

See the individual drugs contained in 572-Trii: Tivicay, Ziagen, and Epivir. Available data are limited due to investigational drug status.

Potential drug interactions

See the individual drugs contained in 572-Trii: Tivicay, Ziagen, and Epivir. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with Tikosym (a heart medicine). Do not take 572Trii with Atripla, Complera, Emtriva, Epivir, Epzicom, Tivicay, Truvada, Viread, or Ziagen, since these medications are already in 572-Trii or they have equivalent medications. Reyataz and Prezista change Tivicay levels, but no dose adjustment is needed. Intelence decreases Tivicay levels by 88%, so your HIV provider would also need to prescribe Kaletra, ritonavir-boosted Prezista, or ritonavir-boosted Reyataz. 572-Trii should be taken two hours before or six hours after taking antacids (like Maalox), the ulcer medication Carafate, iron or calcium supplements or buffered medications. These medications reduce the absorption of Tivicay. Non-antacid acid reflux/heartburn medications (like omeprazole) are okay

to use. Avoid taking with some seizure medicines (carbamazepine, oxcarbazepine, phenobarbital, and phenytoin) and St. John’s wort. Metformin dose may need to be adjusted. Rifampin should be avoided in people with suspected INSTI resistance. 572-Trii has no effect on Versed, methadone, or oral contraceptives. More drug interactions are anticipated, but data are limited right now due to investigational drug status.

More information

ViiV Healthcare applied for FDA approval late last year of this single tablet regimen containing dolutegravir, abacavir, and lamivudine. See the individual drugs contained in 572-Trii—Tivicay, Ziagen, and Epivir, as well as Epzicom (Ziagen/Epivir)—for more information. Based on the current data, 572-Trii appears to be an exciting addition to the current antiretrovirals. It gives us another single-tablet complete regimen. There will be twice-daily dosing for patients with INSTI drug resistance. It should have fewer drug interactions than Stribild and appears to be well tolerated. Check for hepatitis B before starting therapy (see Epivir). 572-Trii is pronounced “572-try.”

See package insert, when available, for more complete information on potential side effects and interactions.

AWP

Doctor’s comments

activist’s comments

TBD; investigational drug at press time

A single-tablet pill combining dolutegravir, abacavir and lamivudine is expected soon. Its simplicity and effectiveness could lead to a renewed enthusiasm for abacavir, especially since its lower efficacy at high viral loads wasn’t an issue when it was combined with dolutegravir. The lingering heart attack controversy with abacavir is still an issue though (see Ziagen).

Yet another fixed dose combination regimen. There is no doubt that, for some patients, having all the meds in one pill is awesome. However, the reality of sorting out toxicities and helping folks to see that even if they struggle with the “easy” approach of a single-tablet regimen, that doesn’t mean they can’t succeed by constructing a regimen the good old fashioned way continues to concern me. The ability to avoid a booster may appeal to some, but overall, it’s difficult to imagine how this particular regimen would surface at the top of a first regimen list. —Dawn Averitt

—Joel Gallant, MD, MPH

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cobicistat cobicistat, or COBI

PKE: pharmacokinetic enhancer (booster); Not an antiretroviral

Potential side effects and toxicity

Side effects seen in clinical studies include diarrhea, nausea, increases in cholesterol and triglycerides, elevated enzymes that break down muscle, and red blood cells in the urine. Some signs of possible kidney malfunction with 10% increase in serum creatinine (SCr) and decreased estimated glomerular filtration rate (e-GFR) were seen in studies. These rarely caused the drug to be stopped. The SCr increase occurred within weeks of starting cobicistat and was reversible. SCr returned to normal within a few days after stopping cobicistat. It did not appear to impact kidney health. Stribild (containing cobicistat) should not be used in patients with poor kidney function or when the patient needs to take other medications which may harm the kidneys.

Potential drug interactions

Cobicistat is expected to interact with many drugs.

Tell your provider or pharmacist about all medications, herbal products, and supplements that you’re taking or thinking of taking, prescribed or not, before starting on a regimen that contains cobicistat. Cobicistat may increase levels of certain calcium channel blockers, beta-blockers, HMG-CoA reductase inhibitors (statins), antiarrhythmics, antidepressants, sedative-hypnotics, erectile dysfunction agents, inhaled corticosteroids, and norgestimate. Caution should be taken, with possible dose adjustments of these medications when used with Stribild. Cobicistat increases serum levels of elvitegravir,

and several protease inhibitors, including Reyataz and Prezista. Sporonox (antifungal) and Biaxin (antibiotic) may increase cobicistat concentrations. Cobicistat may increase Biaxin levels. Rifabutin and some anti-seizure medications, such as Tegretol) and phenytoin (Dilantin) may decrease cobicistat levels. Taking with Olysio is not recommended. The drug interaction list is expected to be as long as Norvir’s. Cobicistat is metabolized by the same drug breakdown pathways as Norvir. Cobicistat may change how the body moves drugs in and out of tissues too. See the package insert when available for more information.

More information

Stribild, which contains cobicistat, was FDA approved in August 2012. Stand-alone cobicistat has not yet been approved by the FDA due to lack of proper “validation of certain quality testing procedures and methods.”

Cobicistat is not an HIV medication. It could be used to boost HIV protease inhibitors (like Norvir). It is being studied in combination with other antiretrovirals (such as Prezista, Emtriva and Reyataz) and as an alternative to Norvir. As an alternative to Norvir, cobicistat’s development has created a lot of excitement. Note, cobicistat shares some of the same side effects of increased cholesterol, increased triglycerides, and stomach upset compared to Norvir. See package insert when available for more complete information on potential side effects and interactions.

Activist’s comments

Activist’s comments

Cobicistat (COBI) is not an antiretroviral medication—it has no activity against HIV. It’s a “pharmacoenhancer” which, like Norvir (ritonavir), “boosts” drug levels of some HIV drugs, including most PIs and the integrase inhibitor elvitegravir. Cobicistat is currently only available in combination with tenofovir, emtricitabine, and elvitegravir in the form of Stribild, but we expect approval of a stand-alone version this year, as well as combinations of cobicistat with Prezista and with Reyataz. The main advantage cobicistat has over Norvir is that it will be made available for co-formulation with other drugs. —Joel Gallant, MD, MPH

Cobicistat (commonly called “COBI”) is a PK (pharmacokinetic) enhancer used to boost antiretroviral drugs by inhibiting their metabolism through the CYP3A4 metabolic pathway. COBI’s initial application to the FDA for marketing as a stand-alone agent was not approved, but that does not appear to be slowing it down. Currently a component in Stribild (the “quad”), COBI seems to be playing the field and may be found in several additional fixed dose combos in the not-sodistant future. —Dawn Averitt

March+April 2014 | positivelyaware.com/cobicistat

Investigational drug at press time; photo unavailable.

STANDARD DOSE

150 mg once a day used in research.

Cobicistat is not an HIV drug, but is used to increase the levels of elvitegravir. Stribild (elvitegravir/cobicistat/ emtricitabine/ tenofovir) is currently the only available formulation with cobicistat. Take a missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. manufacturer

Gilead Sciences gilead.com (800) GILEAD-5 (445-3235) AWP

TBD; drug not yet approved as a standalone agent at press time. Currently available only as a component of the single-tablet regimen Stribild.

59

Egrifta tesamorelin

FOR HIV-RELATED EXCESS BELLY FAT; Not an antiretroviral

STANDARD DOSE

2 mg via subcutaneous (under the skin) injection once daily in the abdomen, rotating injection sites and avoiding scar tissue, bruises, and the navel. manufacturer

EMD Serono, Inc. egrifta.com (877) 714-AXIS (2947) AWP

$2,990.88 for 30 days

Each dose necessitates mixing two 1-mg vials (requiring refrigeration) of Egrifta with one vial of sterile water (stored at room temperature) or one 2-mg vial with one vial of sterile water. Do not use an unopened vial if the solution is colored, cloudy, or contains visible particles.

Once mixed, the vial should be rolled gently between the hands for 30 seconds to ensure reconstitution into a clear, colorless solution and administered right away.

Unopened vials may be stored up to three months at room temperature if refrigeration is unavailable.

A potential complication of HIV, antiretroviral therapy, or both may be the redistribution of adipose tissue (fat), otherwise known as lipodystrophy; reports of prevalence in the U.S. vary widely, anywhere from 2–60% of all HIVpositive patients. Lipohypertrophy (a form of lipodystrophy) is the accumulation of excess visceral adipose tissue (VAT)—deep belly fat surrounding the liver, stomach, and other abdominal organs.

In 2010, Egrifta became the first FDA approved medication to reduce VAT. Egrifta is an analogue of growth hormone releasing factor (GRF) which stimulates the body’s growth hormone production. The effect of this agent appears to be greatest within the first three to six months of initiation.

Two Phase 3 clinical trials found that Egrifta significantly lowered VAT (up to 15–20% on average) at both 26 and 52 weeks. Egrifta may also lower triglycerides (a type of cholesterol). Adverse events were more commonly seen in the groups given Egrifta than in those receiving

placebos. It is important to note that excess VAT returns once Egrifta is discontinued.

Egrifta should not be administered to patients who have pituitary gland tumor(s), pituitary gland surgery, or other pituitary gland problems; active cancer; hypersensitivity to either tesamorelin and/or mannitol; or who are pregnant. Egrifta should be used with caution in patients who have neoplasms (abnormal growth of tissue such as a tumor), elevated insulin-like growth factor 1 (IGF-1), fluid retention, diabetes, or pre-diabetes. The most common side effects include: joint pain, pain in legs and arms, swelling in legs, muscle soreness, tingling, numbness and prickling, nausea, vomiting, rash, and itching. Other warnings include hypersensitivity reactions, injection site reactions, and acute critical illness. Patients receiving Egrifta had a higher risk of developing diabetes compared to those on placebo. Despite initial thoughts that Egrifta may have significant drug-drug interactions with medications that use CYP450 (an enzyme in the liver) for metabolism, a study in healthy volunteers proved otherwise. However, it has not been studied with medications that use other enzymes in the liver—therefore, response to medications that are metabolized through the liver should be monitored for response and adverse reactions.

Long-term safety data is unknown. There have been previous reports of an increased risk of cancer with elevated IFG-1 levels. Other long-term concerns include development of retinopathy.

Fulyzaq crofelemer

For HIV/AIDS-associated diarrhea; Not an antiretroviral

STANDARD DOSE

One 125 mg delayedrelease tablet taken twice a day, with or without food. The tablet should be swallowed whole and not crushed or chewed. manufacturer

Salix Pharmaceuticals fulyzaq.com (919) 862-1000 AWP

In December 2012, the FDA approved Fulyzaq (crofelemer) as the first anti-diarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Currently, what is typically recommended is for the patient to take medication(s) with food and/or use Imodium for symptomatic diarrhea.

Fulyzaq approval was based on a randomized, controlled study of 374 HIV-positive patients taking Fulyzaq or a sugar pill twice daily. ADVENT showed 17.6% of patients taking Fulyzaq had two or less watery bowel movements per week compared to only 8% of patients who took the sugar pill. Fulyzaq was less effective in African Americans in clinical studies. Fulyzaq seems to work best in those who have tried and failed non-prescription anti-diarrheals, have had diarrhea for more than

two years, have more than two watery bowel movements per day, and bowel movements tend to be “pourable” (not clumpy).

At this time, there are no patients who should avoid taking Fulyzaq. If a patient is complaining of diarrhea, an infectious cause should be ruled out prior to initiating Fulyzaq. Some of the most common side effects include bronchitis, cough, flatulence (gas), and increased bilirubin. Fulyzaq may cause fetal harm, based on animal data.

Fulyzaq has not been studied in patients younger than 18 years old and its use in this population cannot be recommended at this time.

Fulyzaq could theoretically inhibit a liver enzyme that helps metabolize drugs (CYP450 3A), but no significant drug interactions occurred among participants in the ADVENT study.

$648.00 / month

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Need info about your HIV meds?

Just enter your drug’s name here.

Looking up your HIV medication in the online version of the Positively Aware HIV Drug Guide is as easy as adding your HIV drug’s name to our URL.

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Serostim somatropin (rDNA)

For HIV-related wasting; Not an antiretroviral

Serostim is recombinant (made in a lab) human growth hormone for treatment of HIV wasting (unintentional loss of weight) or cachexia (general ill health resulting from emaciation), decreased lean body mass (muscle), and loss of physical endurance. Loss of muscle can be difficult to notice or diagnose. Serostim has been shown to increase HIV replication in the test tube; therefore, patients must be taking anti-HIV therapy, known as HAART, in order to be prescribed Serostim.

Most common potential side effects include swelling (especially of the hands and feet), muscle pain, joint pain, numbness, and pain in extremities (the ends of limbs, especially the hands and feet), carpal tunnel syndrome (requiring discontinuation if unresolved by decreasing number of doses), injection site reactions (pain, numbness, redness, or swelling), increased blood fat (triglycerides) and blood sugar, including new or worsening cases of diabetes (sometimes reversible upon stopping Serostim), nausea, and fatigue. More rarely, potential side effects include pancreatitis (watch for persistent severe abdominal pain) and intracranial hypertension (rise in pressure in the skull, with visual changes, headache, nausea, or vomiting). Serostim should be avoided in patients who are acutely ill, have an active cancer, or have diabetic retinopathy (damage to one or both retinas).

Rotate injection sites to avoid injection site reactions.

Do not use while experiencing: cancer or cancer treatment; serious injuries; severe breathing problems; certain

eye diseases related to diabetes; or after critical illness due to complications of abdominal or open heart surgery.

Based on how the drug is broken down in your body, there are some potential drug-drug interactions, though no formal drug studies have been conducted. These theoretically potential interactions include patients on glucocorticoid (such as prednisone) therapy and may require an increased prednisone dose. Others may include medications that are metabolized through the CYP450 enzyme in your liver (like some antiretrovirals, cholesterol medications, or anticonvulsants), or medications like oral estrogen, insulin, or oral diabetes drugs. Be sure to tell your doctor, pharmacist, and/or other providers about all of the medications you are taking, including herbs and supplements, prescribed or not.

If someone is having difficulty paying for Serostim, there are several programs that may be able to assist the patient with acquiring it. These programs include EMD Serono Secured Distribution Program, the AXIS Center, the Serostim Patient Assistance Program (PAP), or a Co-pay Assistance Program. To find out more about these programs, call (877) 714-AXIS (2947).

Go to serostim.com for additional information. Also go to powerusa.org (Program for Wellness Restoration), a community-based resource for information about Serostim and other HIV-related therapies.

STANDARD DOSE

0.1 mg/kg via subcutaneous (under the skin) injection, which may be in the thigh, upper arm, abdomen, or buttock once daily at bedtime (up to 6 mg), rotating injection sites and avoiding scar tissue, bruises, and the navel.

It is available in 4 mg, 5 mg, and 6 mg vials.

The multi-use 4 mg vial is reconstituted with bacteriostatic (containing a biological or chemical agent that stops bacteria from reproducing) water for injection and may be refrigerated for up to 14 days after reconstitution.

The single-use 5 mg and 6 mg vials are reconstituted with sterile water for injection and must be used immediately; after administering the dose, any unused portion should be discarded.

Some loss of the dose can be expected (approximately 10%).

Inject the water into the vial aiming for the glass wall. The vial should be swirled gently in a circular motion until solution is completely dissolved; it must be clear and colorless. Do not shake. Do not inject if solution is cloudy or contains particles. manufacturer

EMD Serono, Inc. serostim.com (877) 714-AXIS (2947) AWP

$2,067.41 / month for 4 mg; $2,584.26 / month for 5 mg; $3,101.11 / month for 6 mg

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Throb, yawn, scratch, and plop Potential drug side effects you should be aware of

L

isted here are the most common side effects for antiretroviral therapy in general, as well as each drug both by class and specifically.

Nucleoside Reverse Transcriptase Inhibitors

Rare but potentially serious side effects with all NRTIs: Enlarged, fatty liver and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, and difficulty breathing.

Potential Drug class side effects:

Combivir (lamivudine / zidovudine)

Remember that some side effects are more common than others, and each person may react differently to the same medicine.

For this reason, a drug regimen can’t be based solely on possible side effects. While taking medications, discuss any physical changes or new symptoms with your doctor and pharmacist. Some side effects can be managed or controlled, while others require intervention or medication changes.

See Epivir and Retrovir.

Emtriva (emtricitabine, or FTC) A very tolerable drug, but side effects may include headache, diarrhea, nausea, and rash. Darkening of the skin on the palms and the soles of the feet has also been reported.

Epivir (lamivudine, or 3TC) A very tolerable drug, but side effects may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise, nasal symptoms, cough, myalgia, peripheral neuropathy, leukopenia, sensitivity to light, depression, rash, abdominal pain, and anemia.

ART There are both benefits and potential side effects associated with HIV medications, known as antiretroviral therapy (ART).

Benefits of ART include restoration of the immune system and reduction in risk of HIV transmission, especially if the viral load is undetectable (less than 50 copies/mL).

Safer sex methods should be practiced, and additional information regarding HIV transmission can be found at aidsinfo.nih.gov.

One potential side effect of ART is known as immune reconstitution inflammatory syndrome (IRIS), which may occur as the immune system regains strength following initiation of therapy. Symptoms of illnesses such as shingles and tuberculosis should be reported to a health care provider immediately.

NRTIs

Epzicom (abacavir / lamivudine) See Ziagen and Epivir.

Retrovir (zidovudine, AZT, or ZDV) Headaches, fever, chills, muscle soreness and/or damage, fatigue, nausea, lipodystrophy, vomiting, GI upset, diarrhea, anorexia, insomnia, blue/black nail discoloration, anemia (low red blood cell count), and neutropenia (low white blood cell count).

Trizivir (abacavir / lamivudine / zidovudine) See Ziagen, Epivir, and Retrovir.

Truvada (emtricitabine / tenofovir)

See Emtriva and Viread. Abdominal distension/pain.

Videx EC (didanosine, or ddI) Peripheral neuropathy, upset stomach, diarrhea, headache, nausea, vomiting, fever, rash, anemia, pancreatitis, eye changes and optic neuritis, increased uric acid levels, insomnia, depression, leukopenia, thrombocytopenia, and body fat redistribution.

Viread (tenofovir, or TDF) Overall fairly well tolerated; however, side effects may include nausea, diarrhea, vomiting, flatulence (gas), high cholesterol, bone changes, kidney toxicities, decreased bone mineral density, and low blood phosphate.

Zerit (stavudine, or d4T) Headache, diarrhea, nausea, vomiting, GI upset, rash, fever, insomnia, dose dependent peripheral neuropathy, myalgias, pancreatitis, lipoatrophy, mitochondrial toxicities (a variety of symptoms caused by cell damage), and elevated cholesterol levels.

Ziagen (abacavir, or ABC) Hypersensitivity reaction, nausea, vomiting, diarrhea, abdominal pain, insomnia, weakness, fatigue, headache, fever, rash, loss of appetite, and potential for increased cardiovascular event, especially in patients with risk factors.

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Throb, yawn, scratch, and plop...

NNRTIs

PIs

Non-Nucleoside Reverse Transcriptase Inhibitors

Potential Drug class side effects: The

Potential Drug class

Common with NNRTIs is rash.

side effects:

Edurant (rilpivirine, or RPV) Insomnia, headache, rash, and depressive disorders.

Intelence (etravirine, or ETR) Rash, diarrhea, nausea, nasopharyngitis (symptoms like a common cold), headache, hypersensitivity, and increased liver enzyme levels.

Rescriptor (delavirdine, or DLV) Increased liver enzyme levels and itchy skin or rash.

Sustiva (efavirenz, or EFV) Central nervous system (CNS) and psychiatric symptoms. Rash, nausea, vomiting, diarrhea, fever, insomnia, and increases in triglycerides, bad cholesterol (LDL), good cholesterol (HDL), and liver enzyme levels. False positive tests for marijuana. Birth defects.

Viramune XR (nevirapine, or NVP) Headache, nausea, vomiting, fever, rash, StevensJohnson syndrome, increased liver enzyme levels, liver damage, and drug-induced hepatitis.

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Protease Inhibitors

most common class side effects of protease inhibitors include gastrointestinal (GI) side effects such as nausea, vomiting, and diarrhea. These occur most frequently at the beginning of therapy. Additional side effects seen with most PIs include increased levels of total cholesterol, triglycerides, and blood sugar, which may be associated with an increased risk of heart disease. Other possible side effects include: lipodystrophy (body fat changes), liver toxicity, osteoporosis, increased bleeding in hemophiliacs, and rash (especially with sulfa allergies). Medical attention should be obtained to determine the severity of a rash.

Aptivus (tipranavir, or TPV) (must be taken with Norvir) GI side effects include: mild diarrhea, nausea, vomiting, and abdominal pain. Other side effects include: headache, fever, fatigue, dry mouth, rash (including sensitivity to sun), dizziness, liver toxicity, and bleeding in the brain.

Use with caution in patients allergic to sulfa drugs. Also see Norvir.

Crixivan (indinavir sulfate, or IDV) GI side effects include: nausea, diarrhea, abdominal/back pain, loss of appetite, dry mouth, sore throat, changes in taste, and indigestion. Other side effects include: headache, fatigue, weakness, painful urination, joint pain, jaundice (yellowing of skin/eyes), hives, liver toxicity, kidney stones, increased bilirubin, itching, ingrown toenails, and hair loss. Kidney stones and jaundice can be minimized or avoided by drinking at least 1.5 liters of water per day.

Invirase (saquinavir, or SQV) (must be taken with Norvir) GI side effects include: diarrhea, abdominal discomfort, vomiting, and nausea. Other side effects include: fatigue, lipodystrophy, and potential heart problems when given with certain other medications. Invirase does not affect cholesterol. Also see Norvir.

Kaletra (lopinavir / ritonavir, or LPV / r) GI side effects include: diarrhea (can be longterm), nausea, vomiting, abdominal pain, and indigestion. Other side effects include: rash, pancreatitis, headache, muscle weakness, and increased liver enzymes, cholesterol, triglycerides, and blood sugar. Potential heart problems can arise when given with certain other medications. Also see Norvir.

Lexiva (fosamprenavir calcium, or FPV)

GI side effects include: nausea, diarrhea (can be long-term), vomiting, changes in taste, and abdominal pain. Other side effects include: headache, fatigue, rash, and liver abnormalities. Lexiva does not usually affect cholesterol, although triglycerides may increase when given with Norvir. Use with caution in patients allergic to sulfa drugs.

Norvir (ritonavir, or RTV) GI side effects include: nausea, vomiting, diarrhea, changes in taste, abdominal pain, and loss of appetite. Other side effects include: weakness, weight loss, headache, dizziness, pancreatitis, liver problems, and tingling/ numbness around the mouth, hands, or feet.

Also seen are increased levels of: cholesterol, triglycerides, and muscle enzymes.

Prezista (darunavir, or DRV) (must be taken with Norvir) GI side effects include: diarrhea, nausea, and abdominal pain. Other side effects include: rash, headache, liver toxicity, and increased blood sugar and cholesterol. Use with caution in patients allergic to sulfa drugs. Also see Norvir.

Reyataz (atazanavir sulfate, or ATV) GI side effects include: nausea (diarrhea and abdominal pain are minimal). Other side effects include: rash, dizziness, increased bilirubin, yellowing of the eyes/skin, kidney stones, increased cholesterol, liver toxicity, potential heart conditions. Reyataz does not affect cholesterol.

Viracept (nelfinavir, or NFV) GI side effects include: mild diarrhea, nausea, and gas. Other side effects include: rash, weakness. Liver toxicity is minimal, and Viracept may be used in patients with hepatitis. Viracept must be taken with a meal of at least 500 calories.

March+April 2014 | positivelyaware.com/drugguide

EIs

Entry inhibitors

Potential Drug class side

No drug class side effects known to date.

effects:

Fuzeon— Fusion Inhibitor (enfuvirtide, T-20, ENF) Injection site reactions (ISRs) such as itching, pain/discomfort, or redness at site of injection, pneumonia, diarrhea, nausea, and fatigue.

Hypersensitivity possible.

Selzentry— CCR5 antagonist (maraviroc, or MVC) Cough, fever, cold, heart problems (chest pain, heart attack, low blood pressure), rash, muscle and joint pain, stomach pain, diarrhea, dizziness, liver toxicity, allergic reaction, upper respiratory tract infection, swelling, sleep disorders, runny nose, and possible increased risk of infections and cancer.

PKE Pharmacokinetic Enhancer (Not an antiretroviral) Potential Drug class side

No drug class side effects known to date.

effects:

cobicistat (or COBI) Investigational drug. Seen in clinical study: diarrhea, nausea, increases in cholesterol and triglycerides, creatine kinase, red blood cells in urine, increased serum creatinine, and decreased estimated glomerular filtration rate (e-GFR). Available data is limited due to investigational status at press time.

STRs

Single-Tablet Regimens

Because STRs contain a combination of medicines from different drug classes, you should look up each drug in the pill.

Potential Drug class side effects:

Atripla

Stribild

(efavirenz / emtricitabine / tenofovir) See Sustiva and Truvada (Emtriva and Viread). Atripla dose cannot be adjusted for people with kidney problems.

Nausea, diarrhea, rash, insomnia, abnormal dreams, and depressive disorders.

(elvitegravir / cobicistat / emtricitabine / tenofovir) See elvitegravir, cobicistat, and Truvada (Emtriva and Viread). In clinical trials, the most common side effects seen with Stribild (more than 10%) include nausea and diarrhea. Less common side effects (less than 10%) include headache, fatigue, abnormal dreams, bone problems, dizziness, insommia, rash, flatulence, changes in kidney function tests, increases in total cholesterol, and elevated liver function tests.

Complera (rilpivirine / emtricitabine / tenofovir) See Edurant and Truvada (Emtriva and Viread). Complera dose cannot be adjusted for people with kidney problems. Insomnia, headache, nausea, dizziness, rash, abnormal dreams, and depressive disorders.

INSTIs

Integrase Strand transfer inhibitors

Potential Drug class side effects:

No class-wide side effects known to date.

Isentress (raltegravir, or RAL) Isentress is generally a very tolerable drug. Side effects seen in clinical trials were uncommon (less than 5%), but can include nausea, headache, insomnia, fatigue, and dizziness. Increased levels of creatine kinase were seen in clinical trials, and resultant muscle pain or damage has been reported.

drugs we have to date. The most common side effects seen in clinical trials (less than 2%) were headache and insomnia.

Tivicay (dolutegravir, or DTG) Tivicay is one of the most well-tolerated

elvitegravir (or EVG) To date, elvitegravir is only available in a combination single-tablet regimen called Stribild. See Stribild. Because elvitegravir is in a combination tablet, side effects may not be solely caused by elvitegravir.

Updated by Walgreens pharmacists Christopher A. Casale, RPH, AAHIVP; Ambrose Delpino, PharmD, AAHIVP; Daniel Jude, PharmD; Mallory Kruckman, PharmD, AAHIVP; Swarup Mehta, PharmD, AAHIVP; Brittany Mills, PharmD, BCACP, AAHIVP; Christopher M. Nguyen, PharmD, AAHIVP; and Nesreen Sweilem.

March+April 2014 | positivelyaware.com/drugguide

69

Individual with HIV

ment options. out my HIV treat ab e or m rn lea chose I was ready to essional and we y healthcare prof m to e uld ok sp I So . He told me it co my HIV regimen of rt pa as S ES ISENTR s and lifest yle. may fit my need fight my HIV and next. r what comes I’m excited fo

In a clinical study lasting more than 4 years (240 weeks), patients being treated with HIV medication for the first time demonstrated that ISENTRESS速 (raltegravir) plus Truvada 速 (emtricitabine/tenofovir

disoproxil fumarate):

INDICATION ISENTRESS is a prescription HIV-1 medicine used with other HIV medicines to treat adults with human immunodeficiency virus (HIV-1) infection. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

The use of other medicines active against HIV-1 in combination with ISENTRESS may increase your ability to fight HIV. ISENTRESS does not cure HIV infection or AIDS. Patients must stay on continuous HIV therapy to control infection and decrease HIV-related illnesses.

IMPORTANT RISK INFORMATION Severe, potentially lifethreatening, and fatal skin reactions and allergic reactions have been reported in some patients taking ISENTRESS. If you develop a rash with any of the following symptoms, stop using ISENTRESS and contact your doctor right away: fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters or sores in mouth, blisters or peeling of skin, redness or swelling of the eyes, swelling of the mouth or face, problems breathing.

Sometimes allergic reactions can affect body organs, like the liver. Contact your doctor right away if you have any of the following signs or symptoms of liver problems: yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale-colored stools/bowel movements, nausea/vomiting,

May reduce viral load to undetectable (less than 50 copies/mL) May significantly increase CD4 cell counts ISENTRESS may not have these effects on all patients Patients had a low rate of these moderate-to-severe common side effects (that interfered with or kept patients from performing daily activities): trouble sleeping (4%), headache (4%), nausea (3%), dizziness (2%), and tiredness (2%).

loss of appetite, pain, aching or tenderness on the right side below the ribs.

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines.

Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your doctor right away if you start having new symptoms after starting your HIV medicine.

People taking ISENTRESS may still develop infections or other conditions associated with HIV infections.

The most common side effects of ISENTRESS include: dizziness, headache, nausea, tiredness and trouble sleeping.

Less common side effects include: allergic reaction, depression, hepatitis, genital herpes, herpes zoster including shingles, kidney failure, kidney stones, stomach pain, suicidal thoughts and actions, vomiting and weakness.

Tell your doctor before beginning ISENTRESS if you have a history of muscle disorders (rhabdomyolysis or myopathy) or increased creatine kinase or if you are taking medications known to cause these conditions such as statins, fenofibrate, gemfibrozil or zidovudine.

Tell your doctor right away if you get unexplained muscle pain, tenderness, or weakness while taking ISENTRESS. This may be a sign of a rare but serious muscle problem that can lead to kidney problems.

Rash occurred more often in patients taking ISENTRESS and darunavir/ritonavir (Prezista 速) together, than with either drug separately, but was generally mild.

These are not all the possible side effects of ISENTRESS. For more information, ask your doctor or pharmacist. Tell your doctor if you have any side effect that bothers you or that does not go away.

Tell your doctor about all your medical conditions, including if you have any allergies, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. ISENTRESS is not recommended for use during pregnancy. Women with HIV should not breastfeed because their babies could be infected with HIV through their breast milk.

Tell your doctor about all the medicines you take, including: prescription medicines like rifampin (a medicine commonly used to treat tuberculosis), non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take antacids, as certain antacids (those containing aluminum and/or magnesium) are not recommended to be taken with ISENTRESS. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call FDA at 1-800-FDA-1088.

Please read the Patient Information on the adjacent page for more detailed information.

Need help paying for ISENTRESS? Call 1-866-350-9232 Talk to your healthcare professional about ISENTRESS and visit isentress.com.

Brands mentioned are the trademarks of their respective owners.

Copyright 息 2013 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. INFC-1049069-0011 11/13

Patient Information ISENTRESS ® (eye sen tris) (raltegravir) Film-Coated Tablets Read this Patient Information before you start taking ISENTRESS and each time you get a refill.

There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is ISENTRESS? ISENTRESS is a prescription HIV medicine used with other HIV medicines to treat adults with human immunodeficiency virus (HIV-1) infection. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

When used with other HIV medicines, ISENTRESS may reduce the amount of HIV in your blood (called “viral load”). ISENTRESS may also help to increase the number of CD4 (T) cells in your blood which help fight off other infections. Reducing the amount of HIV and increasing the CD4 (T) cell count may improve your immune system. This may reduce your risk of death or infections that can happen when your immune system is weak (opportunistic infections).

ISENTRESS does not cure HIV infection or AIDS. People taking ISENTRESS may still develop infections or other conditions associated with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Patients must stay on continuous HIV therapy to control infection and decrease HIV-related illnesses.

Avoid doing things that can spread HIV-1 infection to others: • Do not share needles or other injection equipment.

• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.

• Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Ask your doctor if you have any questions on how to prevent passing HIV to other people.

What should I tell my doctor before taking ISENTRESS? Before taking ISENTRESS, tell your doctor if you: • have liver problems.

• have any other medical conditions.

• take antacids. Certain antacids (those containing aluminum and/or magnesium) are not recommended with ISENTRESS. • are pregnant or plan to become pregnant. It is not known if ISENTRESS can harm your unborn baby.

Pregnancy Registry: You and your doctor will need to decide if taking ISENTRESS is right for you. If you take ISENTRESS while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry. The purpose of the registry is to follow the health of you and your baby.

• are breastfeeding or plan to breastfeed.

- Do not breastfeed if you are taking ISENTRESS. You should not breastfeed if you have HIV because of the risk of passing HIV to your baby.

- Talk with your doctor about the best way to feed your baby.

Tell your doctor about all the medicines you take, including: prescription and nonprescription medicines, vitamins, and herbal supplements. Taking ISENTRESS and certain other medicines may affect each other causing serious side effects. ISENTRESS may affect the way other medicines work and other medicines may affect how ISENTRESS works.

Especially tell your doctor if you take: • antacids. It is not recommended to take ISENTRESS with certain antacids (those containing aluminum and/or magnesium). Talk to your doctor about other antacids you can take.

• rifampin (Rifadin, Rifamate, Rifater, Rimactane), a medicine commonly used to treat tuberculosis.

Ask your doctor or pharmacist if you are not sure whether any of your medicines are included in the list above.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. Do not start any new medicines while you are taking ISENTRESS without first talking with your doctor.

How should I take ISENTRESS? • Take ISENTRESS exactly as prescribed by your doctor.

• You should stay under the care of your doctor while taking ISENTRESS. • Do not change your dose of ISENTRESS or stop your treatment without talking with your doctor first.

• Take ISENTRESS by mouth, with or without food.

• ISENTRESS Film-Coated Tablets must be swallowed whole.

• If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule.

Do not double your next dose or take more than your prescribed dose.

• If you take too much ISENTRESS, call your doctor or go to the nearest emergency room right away.

• Do not run out of ISENTRESS. Get your ISENTRESS refilled from your doctor or pharmacy before you run out.

What are the possible side effects of ISENTRESS? ISENTRESS can cause serious side effects including: • Serious skin reactions and allergic reactions. Severe, potentially life-threatening and fatal skin reactions and allergic reactions have been reported in some patients taking ISENTRESS. If you develop a rash with any of the following symptoms, stop using ISENTRESS and contact your doctor right away: ° fever ° muscle or joint aches ° redness or swelling of the eyes ° generally ill feeling ° blisters or sores in mouth ° swelling of the mouth or face ° extreme tiredness ° blisters or peeling of the skin ° problems breathing

Sometimes allergic reactions can affect body organs, like the liver. Contact your doctor right away if you have any of the following signs or symptoms of liver problems: ° yellowing of the skin or whites of the eyes ° dark or tea colored urine ° pale colored stools/bowel movements ° nausea/vomiting ° loss of appetite ° pain, aching or tenderness on the right side below the ribs • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your doctor right away if you start having new symptoms after starting your HIV medicine.

The most common side effects of ISENTRESS include: • dizziness • tiredness • headache • trouble sleeping • nausea Less common side effects include: • allergic reaction • kidney failure • depression • kidney stones • genital herpes • stomach pain • hepatitis • suicidal thoughts and actions • herpes zoster • vomiting including shingles • weakness Tell your doctor before beginning ISENTRESS if you have a history of muscle disorders (rhabdomyolysis or myopathy) or increased creatine kinase or if you are taking medications known to cause these conditions such as statins, fenofibrate, gemfibrozil or zidovudine.

Tell your doctor right away if you get unexplained muscle pain, tenderness, or weakness while taking ISENTRESS. This may be a sign of a rare but serious muscle problem that can lead to kidney problems.

Rash occurred more often in patients taking ISENTRESS and darunavir/ritonavir together than with either drug separately, but was generally mild.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ISENTRESS. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store ISENTRESS? Film-Coated Tablets: • Store ISENTRESS Film-Coated Tablets at room temperature between 68°F to 77°F (20°C to 25°C).

Keep ISENTRESS and all medicines out of the reach of children.

General information about ISENTRESS Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information Leaflets. Do not use ISENTRESS for a condition for which it was not prescribed.

Do not give ISENTRESS to other people, even if they have the same symptoms you have.

It may harm them.

This leaflet gives you the most important information about ISENTRESS. If you would like to know more, talk with your doctor. You can ask your doctor or pharmacist for information about ISENTRESS that is written for health professionals.

For more information go to www.ISENTRESS.com or call 1-800-622-4477.

What are the ingredients in ISENTRESS? ISENTRESS Film-Coated Tablets: Active ingredient: raltegravir Inactive ingredients: microcrystalline cellulose, lactose monohydrate, calcium phosphate dibasic anhydrous, hypromellose 2208, poloxamer 407 (contains 0.01% butylated hydroxytoluene as antioxidant), sodium stearyl fumarate, magnesium stearate.

The film coating contains: polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc, red iron oxide and black iron oxide.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Distributed by: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Whitehouse Station, NJ 08889, USA Revised November 2013 USPPI-0518-T-1310R024 Copyright © 2007, 2009, 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. INFC-1049069-0011 11/13 U.S. Patent Nos. US 7,169,780

So Many Conditions, So Many Drugs Living longer may lead to more drug interactions

By Stephanie Lynch, RPh and Alice Tseng, PharmD

Photo: ©PURESTOCK

P

eople with HIV are living longer than ever before with improved antiretroviral (ARV) therapies.

As patients age, however, other health conditions become more common, such as heart disease, high cholesterol, high blood pressure, diabetes, osteoporosis, kidney disease, and non-AIDS related cancers. These medical conditions may result from aging in general, long-term side effects of ARVs, risk factors that are more common in HIVpositive patients, or the virus itself.

With older age, the number of medications patients require tends to increase.

They may also be taking vitamins, supplements, and complementary and alternative

medicines (CAM) in addition to their prescription medications. As the number of medications grows, the potential for drugdrug interactions increases.

First things first To better understand drug interactions, it’s helpful to know something about the chemical reactions that may cause them.

Several ARVs may be more likely to cause drug interactions because of their effects on CYP (pronounced “sip”) enzymes.

Cytochrome P450 (CYP450) enzymes are a family of enzymes which work to break down medications in the liver.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are moderate inducers of CYP3A4 enzymes, which means they can speed up how quickly the liver breaks down drugs such as protease inhibitors (PIs) or other drugs that are broken down by this

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73

ARV effects

pathway. The concern is that if ARV drug levels become too low, this may lead to viral breakthrough (detectable viral load), development of ARV resistance, or less than ideal disease management.

Conversely, PIs are strong CYP450 inhibitors and can slow down the metabolism of other drugs resulting in increased drug concentrations. This in turn may lead to a greater chance of side effects.

A common finding in published studies

multiple drugs and aging Here in Toronto, we conducted a recent study, along with our colleagues, comparing the frequency of potential ARV interactions in HIV-positive people who were 50 years of age or older versus HIV-positive adults who were younger than 50. Fifty years of age was used as the definition of “older,” as patients with HIV may age prematurely.

The study included 914 HIV-positive patients attending the specialist-based immunodeficiency clinic in Toronto General Hospital. Fifty-four percent were younger than 50.

When current medications were compared between older and younger patients, older patients were taking more medications than younger ones, nine compared to seven drugs, and this was a statistically significant difference. Older patients were also more likely to be on a ritonavir (Norvir)boosted PI or an integrase inhibitor.

They were also taking a greater number of non-ARV medications. These non-HIV therapies included antibiotics, blood thinning agents, drugs for heart disease, antidepressants, mood stabilizers, sedatives, stomach medications, bone medications, narcotics and other painkillers, hormonal drugs, and CAM. In this study, factors associated with the chance of having one or more potential drug-drug interaction (PDDI) included older age, greater number of non-ARV medications, use of drugs for heart disease, and use of a boosted or unboosted PI. Moreover, for every 10-year increase in age the odds of identifying one or more PDDI was nearly two times higher (1.72) after taking into account gender, race, and type or number of ARVs. In contrast, the use of an integrase inhibitor was associated with a decreased probability of one or more PDDI. 74

is that the use of PIs is associated with a higher risk of having an interaction.

Ritonavir specifically may be involved in potential drug-drug interactions with a variety of drug classes because it is a potent inhibitor of CYP3A4 and p-glycoprotein (a substance that helps pump drugs and toxins out of cells). Ritonavir also induces numerous enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, and glucuronyltransferase.

The results of this study indicate almost half of the patients (44 percent) had PDDIs involving ritonavir, and patients on ritonavir-boosted PIs were 40 times more likely to have a PDDI than patients not taking these drugs.

On the other hand, integrase inhibitors, specifically raltegravir [Isentress], were associated with a decreased likelihood of a PDDI. This is not surprising given raltegravir’s lack of inducing or inhibiting effects on the CYP450 enzyme system.

The newest integrase inhibitor, dolutegravir [Tivicay], also does not significantly affect the cytochrome P450 enzyme system, and is also associated with a low risk of drug interactions.

In contrast, the integrase inhibitor elvitegravir [available only in Stribild] needs to be given with the booster cobicistat. Cobicistat acts similarly to ritonavir in inhibiting CYP3A4 and p-glycoprotein, and may therefore be associated with a higher risk of possible interactions.

Interactions

more ARVs (four compared to three) and were more likely to be virally suppressed compared with patients without PDDIs (92 percent versus 87 percent), possibly due to the greater number of ARVs taken by this group.

Since older patients have been shown to be more adherent to ARVs, this may be another reason for increased virological suppression in patients with orange flag PDDIs in this study as compared to other published research.

Specific interactions In total, 1,718 potential drug-drug interactions (PDDIs) were identified in 63 percent of patients. Of those, 24% occurred between ARVs and the majority, 76%, were between ARVs and non-ARVs. A total of 31 red flag PDDIs were identified in three percent of patients. Fourteen involved a PI and an NNRTI which could have resulted in reduced PI levels and viral breakthrough. Seven patients had a red flag PDDI between salmeterol and a PI. Three patients were on combination ritonavir and Levitra (vardenafil), whereas two patients were on Lexiva (fosamprenavir) and Valium (diazepam). The remaining patients had a red flag interaction between a PI and Cordarone (amiodarone), for atrial fibrillation, Zocor (simvastatin), and Halcion (triazolam).

Of a total of 571 orange flag PDDIs found in 62 percent of patients, the most common were:

n between PIs and nucleosides (28%),

n medications for heart disease (23%),

n narcotics (17%),

n and antidepressants (13%).

We found no statistically significant difference in “red flag” drug interactions by age.

“Red flags” were defined as medication combinations that are contraindicated, or not to be taken together.

Older patients, however, were more likely to have one or more “orange flag” interactions. “Orange flags” included combinations that should not be taken together, could be given with dose adjustment or increased monitoring, or have not been studied for safety, efficacy, or clinical significance. Orange flag PDDIs were found for 71% of older people compared to 55% of younger individuals.

Patients with orange flag PDDIs were on

The most common examples were combinations of ritonavir and analgesics or narcotics (17%), Reyataz (atazanavir) and Viread (tenofovir) (13%), and ritonavir with antidepressants (10%).

Older patients were more likely to have PDDIs involving:

n Sustiva or Atripla (containing efavirenz) or Intelence (etravirine) with Lipitor (atorvastatin),

n PIs with calcium channel blockers or statins (heart and cholesterol medications), and

n ritonavir with beta-blockers (high blood pressure drugs).

March+April 2014 | positivelyaware.com/drugguide

An overall look Overall, this study demonstrated that HIV-positive patients at a specialty clinic treated with ARV therapy are at high risk for experiencing a PDDI. Two-thirds of the patients on ARV therapy had one or more PDDIs identified, with a median of two PDDIs per patient (half of the patients had more than this and half had less). Potential consequences of these interactions included higher risk of drug toxicity or reduced drug effectiveness.

The rate of orange flag interactions was found to be slightly higher in this study when compared to other studies. This may be due to the fact that PDDIs with questionable clinical significance were included; around 8% of orange flag PDDIs in this study fell into that category.

In this study, older patients were significantly more likely than younger patients to be male, men who have sex with men, white and non-immigrants, have a history of an AIDS-defining illness, and have been HIV-positive and on ARV treatment longer.

In the study overall, 78 percent of study participants were male and 90 percent were virologically suppressed.

The study is limited by the fact that PDDI frequency rates may be underestimated, as potential interactions between non-ARV medications were not analyzed.

Secondly, orange flag PDDIs that were already taken into account through dose adjustments were included.

Finally, given the multifactorial nature of PDDIs on patient outcomes, it was not possible to quantify the clinical impact of a PDDI on individual patient health.

Recommendations for patients

medications so that drug-drug interactions can be promptly identified.

It is also recommended that patients check with their physician or pharmacist before starting any new prescription medication, over-the-counter drugs, vitamins, supplements, or complementary and alternative medicines to ensure there are no potential drug-drug interactions with their current medication regimen.

Conclusions Older patients are at a higher risk of experiencing potential drug-drug interactions due to a greater number of non-ARV medications, specifically medications for heart diseases. Increased vigilance should be taken in the care of HIV-positive patients of at least 50 years of age on ARV therapy to prevent drug-drug interactions, to maximize ARV and non-ARV efficacy, and to minimize toxicity.

University of Toronto. She graduated from Dalhousie University with a Bachelor of Science in pharmacy in 2011 and completed an accredited Canadian pharmacy residency program at the Moncton Hospital, Horizon Health Network in 2012.

Alice Tseng, PharmD, is a pharmacist at the Immunodeficiency Clinic, Toronto General Hospital and assistant professor with the faculty of pharmacy, University of Toronto. She is an editor of two popular websites on HIV and hepatitis C drug interaction and pharmacology information— hivclinic.ca and hcvdruginfo.ca. She is also a reviewer of this year’s drug guide.

Reference

Tseng A, Szadkowski L, Walmsley S, et al.

Association of Age With Polypharmacy and Risk of Drug Interactions with Antiretroviral Medications in HIV-Positive Patients. Ann Pharmacother 2013;47(11): 1429-1439.

Stephanie Lynch, RPh , is a pharmacist and doctoral student of pharmacy at the

For every 10-year increase in age, the odds of identifying one or more potential drug-drug interactions was nearly two times higher.

Where available, referral to an expert

Photo: Getty Images

HIV pharmacist for a medication review and assessment of PDDIs is recommended in order to optimize drug treatments.

Patients are highly encouraged to use one pharmacy to fill all of their prescription

Websites such as hivclinic.ca/main/drugs_interact.html, hiv-druginteractions.org or hivinsite.ucsf.edu/insite?page=ar-00-02 are frequently-updated sources of ARV drug interaction information which can be used by physicians and patients to help identify potential drug-drug interactions (PDDIs).

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75

Standard issue DHHS Guidelines for first-time treatment

integrase strand transfer inhibitor

A

NNRTI

Start on one of three types of combination regimens:

DRUG Class Abbreviations

INSTI

non-nucleoside reverse transcriptase inhibitor

regimen should be individualized on the basis of virologic efficacy (suppression of viral load to less than 50 copies per mL), toxicity, pill burden, dosing frequency, drug-drug interaction potential, drug resistance testing results, and co-morbid conditions (such as kidney disease, hepatitis B or C, etc.). For further details of the DHHS recommendations, go to aidsinfo.nih. gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.

Patients new to antiretroviral therapy NNRTI-based regimen

PI-based regimen

+

+

NRTI nucleoside reverse transcriptase inhibitor

PI protease inhibitor

Preferred regimens NNRTI-based

Atripla (EFV 1/FTC/TDF)3 boosted Prezista (DRV/r) (once daily) + Truvada (FTC/TDF)3 boosted Reyataz (ATV/r) + Truvada (FTC/TDF)3

generic name

Isentress (RAL) + Truvada (FTC/TDF)3

Abbreviations

INSTI-based

Stribild (EVG/COBI/FTC/TDF)3 Tivicay (DTG) + Epzicom (3TC/ABC)3, 4 Tivicay (DTG) + Truvada (FTC/TDF)3

Preferred for pregnant women6,7,8 Kaletra (LPV/r) (twice daily) + Combivir (3TC/ZDV)3

PI-based

boosted Reyataz (ATV/r) (once daily) + Combivir (3TC/ZDV)3

Alternative regimens Based on personal characteristics and needs, in some instances, an alternative regimen may actually be a preferred regimen for an individual.

Complera (RPV6, 7/FTC/TDF)3 NNRTI-based

Edurant (RPV) + Epzicom (ABC/3TC)3, 4 Sustiva (EFV)1 + Epzicom (ABC/3TC)3, 4 Kaletra (LPV/r) (once or twice daily) + Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3 boosted Lexiva (FPV/r) (once or twice daily) + Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3

PI-based

boosted Prezista (DRV/r) + Epzicom (ABC/3TC)3, 4 boosted Reyataz (ATV/r) + Epzicom (ABC/3TC)3, 4 INSTI-based

76

+

(preferably boosted)

PI-based

3TC lamivudine ABC abacavir ATV atazanavir COBI cobicistat ddI didanosine DRV darunavir EFV efavirenz EVG elvitegravir FPV fosamprenavir FTC emtricitabine LPV lopinavir MVC maraviroc NVP nevirapine RAL raltegravir RPV rilpivirine r low-dose ritonavir SQV saquinavir TDF tenofovir ZDV zidovudine (or AZT)

INSTI-based regimen

Isentress (RAL) + Epzicom (ABC/3TC)3, 4

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THE 2014 HIV DRUG GUIDE

Other antiretroviral regimens Regimens that may be selected for some patients but are less satisfactory than preferred or alternative regimens.

Edurant (RPV) + Combivir (3TC/ZDV)3 NNRTI-based

Sustiva (EFV 1) + Combivir (3TC/ZDC)3 Viramune (NVP2) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3 boosted Invirase (SQV/r) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3 Kaletra (LPV/r) + Combivir (3TC/ZDV)3

PI-based

boosted Lexiva (FPV/r) + Combivir (3TC/ZDV)3 boosted Prezista (DRV/r) + Combivir (3TC/ZDV)3 boosted Reyataz (ATV/r) + Combivir (3TC/ZDV)3 Reyataz (ATV) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4

INSTI-based

Isentress (RAL) + Combivir (3TC/ZDV)3

CCR5 antagonistbased regimen

Selzentry (MVC)5 + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3

FOOTNOTES

1. Except during first trimester of pregnancy or in women with high pregnancy potential.

2. Nevirapine (Viramune) should not be initiated in women with CD4+ T-cell count greater than 250 cells/mm3 or in men with CD4+ T-cell count greater than 400 cells/mm3.

3. Emtriva (emtricitabine, FTC) and lamivudine (Epivir, 3TC) are interchangeable.

4. ABC should not be used in people who test positive for HLA-B*5701.

5. MVC may be considered in people who have only CCR5-tropic HIV. 6. Perinatal guidelines panel recommends that Sustiva (efavirenz, also found in Atripla) be continued in women obtaining antenatal care in the first trimester if viral load is suppressed.

7. Perinatal guidelines panel recommends that pregnant women tolerating a nevirapine-containing regimen (brand name Viramune) who are virologically suppressed should continue regimen regardless of CD4 count.

8. In general, perinatal guidelines panel recommends that pregnant women obtaining antenatal care in the first trimester should continue their HIV treatment, assuming the regimen used is tolerated and effective in suppressing viral replication.

These combinations are among those available as co-formulated fixed dose combinations

EFV/FTC/TDF (Atripla)

3TC/ZDV (Combivir) RPV/FTC/TDF (Complera) ABC/3TC (Epzicom) LPV/r (Kaletra) EVG/COBI/FTC/TDF (Stribild) FTC/TDF (Truvada)

* Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.

Available at aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section accessed January 31, 2014, Tables 5a and 5b. ** Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed January 31, 2014; Table 5 and Recommendations.

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The

one

for me

Patient model. Pill shown is not actual size.

What is COMPLERA? COMPLERA is a prescription HIV medicine that is used as a complete regimen to treat HIV-1 in adults who have never taken HIV medicines before and who have an amount of HIV in their blood (this is called “viral load”) that is no more than 100,000 copies/mL. COMPLERA contains 3 medicines – rilpivirine, emtricitabine and tenofovir disoproxil fumarate. It is not known if COMPLERA is safe and effective in children under the age of 18 years. ®

COMPLERA® does not cure HIV-1 infection or AIDS. To control HIV-1 infection and decrease HIV-related illnesses you must keep taking COMPLERA. Avoid doing things that can spread HIV-1 to others: always practice safer sex and use condoms to lower the chance of sexual contact with body fluids; never reuse or share needles or other items that have body fluids on them, do not share personal items that may contain bodily fluids. Ask your healthcare provider if you have questions about how to reduce the risk of passing HIV-1 to others.

IMPORTANT SAFETY INFORMATION What is the most important information you should know about COMPLERA? COMPLERA® can cause serious side effects: • Build-up of an acid in your blood (lactic acidosis), which is a serious medical emergency. Symptoms of lactic acidosis include feeling very weak or tired, unusual (not normal) muscle pain, trouble breathing, stomach pain with nausea or vomiting, feeling cold, especially in your arms and legs, feeling dizzy or lightheaded, and/or a fast or irregular heartbeat.

• Serious liver problems. The liver may become large (hepatomegaly) and fatty (steatosis). Symptoms of liver problems include your skin or the white part of your eyes turns yellow (jaundice), dark “tea-colored” urine, light-colored bowel movements (stools), loss of appetite for several days or longer, nausea, and/or stomach pain.

• You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking COMPLERA for a long time.

In some cases, these serious conditions have led to death. Call your healthcare provider right away if you have any symptoms of these conditions.

• Worsening of hepatitis B (HBV) infection. If you also have HBV and stop taking COMPLERA, your hepatitis may suddenly get worse. Do not stop taking COMPLERA without first talking to your healthcare provider, as they will need to monitor your health. COMPLERA is not approved for the treatment of HBV.

Who should not take COMPLERA? Do not take COMPLERA if you have ever taken other anti-HIV medicines.

COMPLERA may change the effect of other medicines and may cause serious side effects. Your healthcare provider may change your other medicines or change their doses.

Do not take COMPLERA if you also take these medicines: • anti-seizure medicines: carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol-XR, Teril, Epitol); oxcarbazepine (Trileptal), phenobarbital (Luminal), phenytoin (Dilantin, Dilantin-125, Phenytek) • anti-tuberculosis medicines: rifabutin (Mycobutin), rifampin (Rifater, Rifamate, Rimactane, Rifadin) and rifapentine (Priftin) • proton pump inhibitors for stomach or intestinal problems: esomeprazole (Nexium, Vimovo), lansoprazole (Prevacid), dexlansoprazole (Dexilant), omeprazole (Prilosec), pantoprazole sodium (Protonix), rabeprazole (Aciphex) • more than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate • St. John’s wort (Hypericum perforatum) If you are taking COMPLERA you should not take other HIV medicines or other medicines containing tenofovir (Viread, Truvada, Stribild or Atripla); other medicines containing emtricitabine or lamivudine (Emtriva, Combivir, Epivir, Epivir-HBV, Epzicom, Trizivir, Atripla, Stribild or Truvada); rilpivirine (Edurant) or adefovir (Hepsera).

In addition, tell your healthcare provider if you are taking the following medications because they may interfere with how COMPLERA works and may cause side effects: • certain antacid medicines containing aluminum, magnesium hydroxide, or calcium carbonate (examples: Rolaids, TUMS). These medicines must be taken at least 2 hours before or 4 hours after COMPLERA. • medicines to block stomach acid including cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine HCL (Zantac). These medicines must be taken at least 12 hours before or 4 hours after COMPLERA. • any of these medicines: clarithromycin (Biaxin); erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Ilosone), fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral) methadone (Dolophine); posaconazole (Noxafil), telithromycin (Ketek) or voriconazole (Vfend).

• medicines that are eliminated by the kidneys like acyclovir (Zovirax), cidofovir (Vistide), ganciclovir (Cytovene IV, Vitrasert), valacyclovir (Valtrex) and valganciclovir (Valcyte).

COMPLERA.

A complete HIV treatment in only 1 pill a day.

COMPLERA is for adults who have never taken HIV-1 medicines before and have no more than 100,000 copies/mL of virus in their blood.

Ask your healthcare provider if it’s the one for you.

These are not all the medicines that may cause problems if you take COMPLERA. Tell your healthcare provider about all prescription and nonprescription medicines, vitamins, or herbal supplements you are taking or plan to take.

The most common side effects reported with COMPLERA are trouble sleeping (insomnia), abnormal dreams, headache, dizziness, diarrhea, nausea, rash, tiredness, and depression. Some side effects also reported include vomiting, stomach pain or discomfort, skin discoloration (small spots or freckles) and pain.

Before taking COMPLERA, tell your healthcare provider if you: liver problems, including hepatitis B or C virus infection, or have abnormal liver tests • Have kidney problems • Have ever had a mental health problem • Have bone problems • Are pregnant or planning to become pregnant. It is not known if COMPLERA can harm your unborn child • Are breastfeeding: Women with HIV should not breastfeed because they can pass HIV through their milk to the baby. Also, COMPLERA may pass through breast milk and could cause harm to the baby

This is not a complete list of side effects. Tell your healthcare provider or pharmacist if you notice any side effects while taking COMPLERA, and call your healthcare provider for medical advice about side effects.

• Have

COMPLERA can cause additional serious side effects: • New or worsening kidney problems, including kidney failure. If you have had kidney problems, or take other medicines that may cause kidney problems, your healthcare provider may need to do regular blood tests.

• Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms: feeling sad or hopeless, feeling anxious or restless, have thoughts of hurting yourself (suicide) or have tried to hurt yourself.

• Changes in liver enzymes: People who have had hepatitis B or C, or who have had changes in their liver function tests in the past may have an increased risk for liver problems while taking COMPLERA. Some people without prior liver disease may also be at risk. Your healthcare provider may need to check your liver enzymes before and during treatment with COMPLERA. • Bone problems can happen in some people who take COMPLERA. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do additional tests to check your bones.

• Changes in body fat can happen in people taking HIV medicine.

• Changes in your immune system. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new symptoms after starting COMPLERA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088.

Additional Information about taking COMPLERA:

• Always take COMPLERA exactly as your healthcare provider tells you to take it.

• Take COMPLERA with food. Taking COMPLERA with food is important to help get the

right amount of medicine in your body. (A protein drink does not replace food. If your healthcare provider stops COMPLERA, make certain you understand how to take your new medicine and whether you need to take your new medicine with a meal.)

Stay under the care of your healthcare provider during treatment with COMPLERA and see your healthcare provider regularly.

Please see Brief Summary of full Prescribing Information with important warnings on the following pages.

Learn more at www.COMPLERA.com

BriefBrief Summary Summary of full of Prescribing full Prescribing Information Information

• Worsening Worsening of Hepatitis of Hepatitis B infection.

B infection.

If youIf have you have hepatitis hepatitis B virus B virus (HBV)(HBV) infection infection and and taketake COMPLERA, COMPLERA, your your HBV HBV may may get worse get worse (flare-up) (flare-up) if youif stop you stop COMPLERA COMPLERA (kom-PLEH-rah) (kom-PLEH-rah) taking taking COMPLERA. COMPLERA. A “flare-up” A “flare-up” is when is when your your HBV HBV infection infection suddenly suddenly returns returns (emtricitabine, (emtricitabine, rilpivirine, rilpivirine, tenofovir tenofovir disoproxil disoproxil fumarate) fumarate) tablets tablets in a in worse a worse way way thanthan before. before.

COMPLERA COMPLERA is notis approved not approved for the for treatment the treatment of of BriefBrief summary summary of full of Prescribing full Prescribing Information.

Information.

For more For more information, information, please please see see HBV,HBV, so you so must you must discuss discuss your your HBV HBV withwith your your healthcare healthcare provider. provider. the full the Prescribing full Prescribing Information Information including including Patient Patient Information.

Information.

– Do–not Do let notyour let your COMPLERA COMPLERA run out. run out.

RefillRefi your ll your prescription prescription or talk or talk to your to your healthcare healthcare provider provider before before your your COMPLERA COMPLERA is allisgone. all gone.

WhatWhat is COMPLERA? is COMPLERA? – Do–not Do stop not stop taking taking COMPLERA COMPLERA without without first fitalking rst talking to your to your healthcare healthcare • COMPLERA • COMPLERA is a prescription is a prescription HIV (Human HIV (Human Immunodefi Immunodefi ciency ciency Virus) Virus) medicine medicine provider. provider. that that is used is used to treat to treat HIV-1HIV-1 in adults in adults – If you – If stop you stop taking taking COMPLERA, COMPLERA, your your healthcare healthcare provider provider will need will need to check to check – who – who havehave never never takentaken HIV medicines HIV medicines before, before, and and your your health health oftenoften and and do blood do blood teststests regularly regularly to check to check your your HBV HBV infection. infection.

– who – who havehave an amount an amount of HIV of in HIVtheir in their bloodblood (this(this is called is called ‘viral‘viral load’)load’) that that Tell your Tell your healthcare healthcare provider provider aboutabout any new any new or unusual or unusual symptoms symptoms you may you may is noismore no more thanthan 100,000 100,000 copies/mL. copies/mL. YourYour healthcare healthcare provider provider will measure will measure havehave afterafter you stop you stop taking taking COMPLERA. COMPLERA. your your viralviral load.load.

WhoWho should should not take not take COMPLERA? COMPLERA? (HIV (HIV is theis virus the virus that that causes causes AIDSAIDS (Acquired (Acquired Immunodefi Immunodefi ciency ciency Syndrome)).

Syndrome)).

Do not Do take not take COMPLERA COMPLERA if: if: • COMPLERA • COMPLERA contains contains 3 medicines 3 medicines – rilpivirine, – rilpivirine, emtricitabine, emtricitabine, tenofovir tenofovir • your • your HIV infection HIV infection has been has been previously previously treated treated withwith HIV medicines.

HIV medicines. disoproxil disoproxil fumarate fumarate – combined – combined in one in tablet. one tablet.

It is Ita complete is a complete regimen regimen to to • • you are you taking are taking any of any the of following the following medicines: medicines: treattreat HIV-1HIV-1 infection infection and and should should not be notused be used withwith otherother HIV medicines.

HIV medicines.

– anti-seizure – anti-seizure medicines: medicines: carbamazepine carbamazepine (Carbatrol, (Carbatrol, Equetro, Equetro, Tegretol, Tegretol, • It is • It notis known not known if COMPLERA if COMPLERA is safe is safe and and effective effective in children in children underunder the age the age Tegretol-XR, Tegretol-XR, Teril,Teril, Epitol); Epitol); oxcarbazepine oxcarbazepine (Trileptal); (Trileptal); phenobarbital phenobarbital of 18ofyears 18 years old. old.

(Luminal); (Luminal); phenytoin phenytoin (Dilantin, (Dilantin, Dilantin-125, Dilantin-125, Phenytek) Phenytek) • COMPLERA • COMPLERA doesdoes not cure not cure HIV infection HIV infection or AIDS. or AIDS. You must You must stay stay on continuous on continuous – – anti-tuberculosis anti-tuberculosis (anti-TB) (anti-TB) medicines: medicines: rifabutin rifabutin (Mycobutin); (Mycobutin); rifampin rifampin therapy therapy to control to control HIV infection HIV infection and and decrease decrease HIV-related HIV-related illnesses. illnesses.

(Rifater, (Rifater, Rifamate, Rifamate, Rimactane, Rimactane, Rifadin); Rifadin); rifapentine rifapentine (Priftin) (Priftin) • Ask• your Ask your healthcare healthcare provider provider if youif have you have any questions any questions about about how how to to – proton pumppump inhibitor inhibitor (PPI)(PPI) medicine medicine for certain for certain stomach stomach or intestinal or intestinal prevent prevent passing passing HIV to HIVother to other people. people.

Do not Do share not share or re-use or re-use needles needles or other or other – proton problems: problems: esomeprazole esomeprazole (Nexium, (Nexium, Vimovo); Vimovo); lansoprazole lansoprazole (Prevacid); (Prevacid); injection injection equipment, equipment, and and do not do share not share personal personal itemsitems that that can have can have bloodblood or or dexlansoprazole (Dexilant); (Dexilant); omeprazole omeprazole (Prilosec, (Prilosec, Zegerid); Zegerid); pantoprazole pantoprazole bodybody fluidsfluids on them, on them, like toothbrushes like toothbrushes and and razorrazor blades. blades.

Always Always practice practice safersafer dexlansoprazole sodium sodium (Protonix); (Protonix); rabeprazole rabeprazole (Aciphex) (Aciphex) sex by sexusing by using a latex a latex or polyurethane or polyurethane condom condom to lower to lower the chance the chance of sexual of sexual contact contact withwith semen, semen, vaginal vaginal fluidsfluids or blood. or blood.

– more – more thanthan 1 dose 1 dose of theof steroid the steroid medicine medicine dexamethasone dexamethasone or dexamethasone or dexamethasone sodium sodium phosphate phosphate WhatWhat is theis most the most important important information information I should I should knowknow about about COMPLERA? COMPLERA? – St.–John’s St. John’s wortwort (Hypericum (Hypericum perforatum) perforatum) COMPLERA COMPLERA can can cause cause serious serious sideside effects, effects, including: including: • If you • If take you take COMPLERA, COMPLERA, you should you should not take: not take: • Build-up • Build-up of anofacid an acid in your in your bloodblood (lactic (lactic acidosis). acidosis).

Lactic Lactic acidosis acidosis can can happen happen in some in some people people who who taketake COMPLERA COMPLERA or similar or similar (nucleoside (nucleoside analogs) analogs) – Other – Other medicines medicines that that contain contain tenofovir tenofovir (Atripla, (Atripla, Stribild, Stribild, Truvada, Truvada, Viread) Viread) medicines. medicines.

Lactic Lactic acidosis acidosis is a serious is a serious medical medical emergency emergency that that can lead can lead to to – Other – Other medicines medicines that that contain contain emtricitabine emtricitabine or lamivudine or lamivudine (Combivir, (Combivir, death. death.

Lactic Lactic acidosis acidosis can be canhard be hard to identify to identify early,early, because because the symptoms the symptoms Emtriva, Emtriva, EpivirEpivir or Epivir-HBV, or Epivir-HBV, Epzicom, Epzicom, Trizivir, Trizivir, Atripla, Atripla, Truvada, Truvada, Stribild) Stribild) couldcould seemseem like symptoms like symptoms of other of other health health problems. problems.

Call Call youryour healthcare healthcare – – rilpivirine rilpivirine (Edurant) (Edurant) provider provider rightright awayaway if youif get you any get of anythe of following the following symptoms symptoms which which couldcould be signs be signs of lactic of lactic acidosis: acidosis: – adefovir – adefovir (Hepsera) (Hepsera) – feel– very feel very weakweak or tired or tired WhatWhat should should I tellI my tellhealthcare my healthcare provider provider before before taking taking COMPLERA? COMPLERA? – have – have unusual unusual (not (not normal) normal) muscle muscle painpain Before Before you take you take COMPLERA, COMPLERA, tell your tell your healthcare healthcare provider provider if you: if you: – have – have trouble trouble breathing breathing • have • have or had or had liverliver problems, problems, including including hepatitis hepatitis B or BC or virus C virus infection, infection, kidney kidney problems, mental mental health health problem problem or bone or bone problems problems – have – have stomach stomach painpain withwith nausea nausea (feeling (feeling sick sick to your to your stomach) stomach) or vomiting or vomiting problems, • are• pregnant are pregnant or plan or plan to become to become pregnant. pregnant.

It is Itnotis known not known if COMPLERA if COMPLERA can can – feel– cold, feel cold, especially especially in your in your armsarms and and legs legs harmharm your your unborn unborn child.child.

– feel– dizzy feel dizzy or lightheaded or lightheaded Pregnancy Pregnancy Registry.

Registry.

ThereThere is a pregnancy is a pregnancy registry registry for women for women who who taketake – have – have a fast a fast or irregular or irregular heartbeat heartbeat antiviral antiviral medicines medicines during during pregnancy. pregnancy.

The purpose The purpose of this of this registry registry is toiscollect to collect information aboutabout the health the health of you of and you and your your baby.baby.

Talk Talk to your to your healthcare healthcare • Severe • Severe liverliver problems. problems.

Severe Severe liverliver problems problems can happen can happen in people in people who who taketake information provider provider aboutabout how how you can you take can take part part in this in this registry. registry.

COMPLERA. COMPLERA. In some In some cases, cases, thesethese liverliver problems problems can lead can lead to death. to death.

YourYour liverliver may may become become largelarge (hepatomegaly) (hepatomegaly) and and you may you may develop develop fat infatyour in your liverliver • are• breast-feeding are breast-feeding or plan or plan to breast-feed. to breast-feed.

You You should should not breastfeed not breastfeed if youif you (steatosis). (steatosis).

Call Call youryour healthcare healthcare provider provider rightright awayaway if youif get you any get of anythe of the havehave HIV because HIV because of the of risk the risk of passing of passing HIV to HIVyour to your baby.baby.

Do not Do breastfeed not breastfeed following following symptoms symptoms of liver of liver problems: problems: if youif are you taking are taking COMPLERA. COMPLERA. At least At least two of twotheof medicines the medicines contained contained in in COMPLERA COMPLERA can be canpassed be passed to your to your babybaby in your in your breast breast milk.milk.

We do Wenot do know not know – your – your skin skin or theor white the white part part of your of your eyeseyes turnsturns yellow yellow (jaundice) (jaundice) whether whether this this couldcould harmharm your your baby.baby.

Talk Talk to your to your healthcare healthcare provider provider aboutabout the the – dark – dark “tea-colored” “tea-colored” urineurine bestbest way way to feed to feed your your baby.baby.

– light-colored – light-colored bowelbowel movements movements (stools) (stools) Tell your Tell your healthcare healthcare provider provider about about all the all medicines the medicines you take, you take, including including ®

– loss – loss of appetite of appetite for several for several daysdays or longer or longer

prescription prescription and and nonprescription nonprescription medicines, medicines, vitamins, vitamins, and and herbal herbal supplements. supplements.

– nausea – nausea

•

– stomach – stomach painpain •

•

®

You• You maymay be more be more likelylikely to get to lactic get lactic acidosis acidosis or severe or severe liverliver problems problems if if you are you female, are female, veryvery overweight overweight (obese), (obese), or have or have beenbeen taking taking COMPLERA COMPLERA for afor long a long time.time.

• COMPLERA COMPLERA maymay affect affect the way the way otherother medicines medicines work,work, and and otherother medicines medicines maymay affect affect how how COMPLERA COMPLERA works, works, and and maymay cause cause serious serious sideside effects. effects.

If If you take you take certain certain medicines medicines withwith COMPLERA, COMPLERA, the amount the amount of COMPLERA of COMPLERA in your in your bodybody may may be too below too and low and it may it may not work not work to help to help control control your your HIV infection.

HIV infection.

The HIV The virus HIV virus in your in your bodybody may may become become resistant resistant to COMPLERA to COMPLERA or other or other HIV HIV medicines medicines that that are like are it. like it.

The most The most common common side side effects effects of COMPLERA of COMPLERA include: include: Especially Especially tell your tell your healthcare healthcare provider provider if youif take: you take: an •antacid an antacid medicine medicine that that contains contains aluminum, aluminum, magnesium magnesium hydroxide, hydroxide, or or • trouble • trouble sleeping sleeping (insomnia) (insomnia) calcium calcium carbonate. carbonate.

If youIf take you take an antacid an antacid during during treatment treatment withwith COMPLERA, COMPLERA, • abnormal • abnormal dreams dreams taketake the antacid the antacid at least at least 2 hours 2 hours before before or atorleast at least 4 hours 4 hours afterafter you you taketake COMPLERA. COMPLERA. • headache • headache • a medicine • a medicine to block to block the acid the acid in your in your stomach, stomach, including including cimetidine cimetidine • dizziness • dizziness (Tagamet), (Tagamet), famotidine famotidine (Pepcid), (Pepcid), nizatidine nizatidine (Axid), (Axid), or ranitidine or ranitidine hydrochloride hydrochloride • diarrhea • diarrhea (Zantac).

(Zantac).

If youIf take you take one of onethese of these medicines medicines during during treatment treatment withwith • nausea COMPLERA, COMPLERA, taketake the acid the acid blocker blocker at least at least 12 hours 12 hours before before or atorleast at least 4 hours 4 hours • nausea afterafter you take you take COMPLERA. COMPLERA. • rash • rash •

•

any• of anythese of these medicines medicines (if taken (if taken by mouth by mouth or injection): or injection):

•

– clarithromycin – clarithromycin (Biaxin) (Biaxin)

• tiredness tiredness

•

• depression depression

– erythromycin – erythromycin (E-Mycin, (E-Mycin, Eryc,Eryc, Ery-Tab, Ery-Tab, PCE,PCE, Pediazole, Pediazole, Ilosone) Ilosone)

•

• vomiting vomiting

– itraconazole – itraconazole (Sporanox) (Sporanox)

•

• stomach stomach painpain or discomfort or discomfort

– ketoconazole – ketoconazole (Nizoral) (Nizoral)

•

skin• skin discoloration discoloration (small (small spotsspots or freckles) or freckles)

•

• pain pain

– methadone – methadone (Dolophine) (Dolophine) – posaconazole – posaconazole (Noxafi (Noxafi l) l) – telithromycin – telithromycin (Ketek) (Ketek) – voriconazole – voriconazole (Vfend) (Vfend) •

Additional Additional common common side side effects effects include: include:

– fluconazole – fluconazole (Diflucan) (Diflucan)

Tell your Tell your healthcare healthcare provider provider if youif have you have any side any side effecteffect that that bothers bothers you or youthat or that doesdoes not go notaway. go away.

TheseThese are not are all notthe all possible the possible side side effects effects of COMPLERA. of COMPLERA. For more For more information, information, ask your ask your healthcare healthcare provider provider or pharmacist. or pharmacist.

• medicines medicines that that are eliminated are eliminated by the by kidney, the kidney, including including acyclovir acyclovir (Zovirax), (Zovirax), your your doctor doctor for medical for medical advice advice aboutabout side side effects. effects.

You may You may report report side side cidofovir cidofovir (Vistide), (Vistide), ganciclovir ganciclovir (Cytovene (Cytovene IV, Vitrasert), IV, Vitrasert), valacyclovir valacyclovir (Valtrex), (Valtrex), Call Call effects effects to FDA to FDA at 1-800-FDA-1088 at 1-800-FDA-1088 (1-800-332-1088).

(1-800-332-1088). and and valganciclovir valganciclovir (Valcyte) (Valcyte)

WhatWhat are the are possible the possible sideside effects effects of COMPLERA? of COMPLERA? COMPLERA COMPLERA can can cause cause serious serious sideside effects, effects, including: including: • See • See “What “What is theis most the most important important information information I should I should knowknow about about COMPLERA?” COMPLERA?” •

• New New or worse or worse kidney kidney problems, problems, including including kidney kidney failure, failure, can happen can happen in in somesome people people who who taketake COMPLERA. COMPLERA. YourYour healthcare healthcare provider provider should should do blood do blood teststests to check to check your your kidneys kidneys before before starting starting treatment treatment withwith COMPLERA. COMPLERA. If youIf you havehave had had kidney kidney problems problems in thein past the past or need or need to take to take another another medicine medicine that that can cause can cause kidney kidney problems, problems, your your healthcare healthcare provider provider may may needneed to dotoblood do blood teststests to check to check your your kidneys kidneys during during your your treatment treatment withwith COMPLERA. COMPLERA.

•

• Depression Depression or mood or mood changes. changes.

Tell your Tell your healthcare healthcare provider provider rightright awayaway if if you have you have any of anythe of following the following symptoms: symptoms:

– feeling – feeling sad or sadhopeless or hopeless

HowHow should should I take I take COMPLERA? COMPLERA? •

• Stay Stay under under the care the care of your of your healthcare healthcare provider provider during during treatment treatment withwith COMPLERA. COMPLERA.

•

• Take Take COMPLERA COMPLERA exactly exactly as your as your healthcare healthcare provider provider tellstells you to youtake to take it. it.

•

• Always Always taketake COMPLERA COMPLERA withwith food.food.

Taking Taking COMPLERA COMPLERA withwith foodfood is important is important to help to help get the get right the right amount amount of medicine of medicine in your in your body.body.

A protein A protein drinkdrink is notis not a substitute a substitute for food. for food.

If your If your healthcare healthcare provider provider decides decides to stop to stop COMPLERA COMPLERA and and you are you switched are switched to new to new medicines medicines to treat to treat HIV that HIV that includes includes rilpivirine rilpivirine tablets, tablets, the rilpivirine the rilpivirine tablets tablets should should be taken be taken only only withwith a meal. a meal.

•

Do •not Do change not change your your dosedose or stop or stop taking taking COMPLERA COMPLERA without without first fitalking rst talking withwith your your healthcare healthcare provider. provider.

See your See your healthcare healthcare provider provider regularly regularly whilewhile taking taking COMPLERA. COMPLERA.

•

• If miss If you you miss a dose a dose of COMPLERA of COMPLERA within within 12 hours 12 hours of theof time the time you usually you usually taketake it, take it, take your your dosedose of COMPLERA of COMPLERA withwith foodfood as soon as soon as possible. as possible.

Then,Then, taketake your your next next dosedose of COMPLERA of COMPLERA at the at regularly the regularly scheduled scheduled time.time.

If youIf miss you miss a dose a dose of COMPLERA of COMPLERA by more by more thanthan 12 hours 12 hours of theof time the time you usually you usually taketake it, wait it, wait and and thenthen taketake the next the next dosedose of COMPLERA of COMPLERA at the at regularly the regularly scheduled scheduled time.time.

•

Do •not Do take not take moremore thanthan your your prescribed prescribed dosedose to make to make up for upafor missed a missed dose.dose.

– feeling – feeling anxious anxious or restless or restless – have – have thoughts thoughts of hurting of hurting yourself yourself (suicide) (suicide) or have or have triedtried to hurt to hurt yourself yourself •

• Change Change in liver in liver enzymes. enzymes.

People People withwith a history a history of hepatitis of hepatitis B or BC or virus C virus infection infection or who or who havehave certain certain liverliver enzyme enzyme changes changes may may havehave an increased an increased risk risk of developing of developing new new or worsening or worsening liverliver problems problems during during treatment treatment withwith COMPLERA. COMPLERA. LiverLiver problems problems can can also also happen happen during during treatment treatment withwith COMPLERA COMPLERA in people in people without without a history a history of liver of liver disease. disease.

YourYour healthcare healthcare provider provider may may needneed to dototests do tests to check to check your your liverliver enzymes enzymes before before and and during during treatment treatment withwith COMPLERA. COMPLERA.

This This BriefBrief Summary Summary summarizes summarizes the most the most important important information information aboutabout COMPLERA. COMPLERA. If youIf would you would like more like more information, information, talk talk withwith your your healthcare healthcare provider. provider.

You can You also can also ask your ask your healthcare healthcare provider provider or pharmacist or pharmacist for for information information aboutabout COMPLERA COMPLERA that that is written is written for health for health professionals, professionals, or call or call 1-800-445-3235 1-800-445-3235 or goortogowww.COMPLERA.com to www.COMPLERA.com

•

• Bone Bone problems problems can happen can happen in some in some people people who who taketake COMPLERA. COMPLERA. BoneBone Issued: Issued: JuneJune 20132013 problems problems include include bonebone pain,pain, softening softening or thinning or thinning (which (which may may leadlead to to fractures). fractures).

YourYour healthcare healthcare provider provider may may needneed to dotoadditional do additional teststests to check to check your your bones. bones.

•

• Changes Changes in body in body fat can fat happen can happen in people in people taking taking HIV medicine.

HIV medicine.

TheseThese changes changes may may include include increased increased amount amount of fatofinfatthein upper the upper backback and and neckneck (“buffalo (“buffalo hump”), hump”), breast, breast, and and around around the main the main part part of your of your bodybody (trunk). (trunk).

LossLoss of fatoffrom fat from the legs, the legs, armsarms and and faceface may may also also happen. happen.

The cause The cause and and longlong termterm health health effecteffect of these of these conditions conditions are not are known. not known.

•

• Changes Changes in your in your immune immune system system (Immune (Immune Reconstitution Reconstitution Syndrome) Syndrome) can can happen happen whenwhen you start you start taking taking HIV medicines.

HIV medicines.

YourYour immune immune system system may may get get stronger stronger and and beginbegin to fight to fiinfections ght infections that that havehave beenbeen hidden hidden in your in your bodybody for for a long a long time.time.

Tell your Tell your healthcare healthcare provider provider if youif start you start having having new new symptoms symptoms afterafter starting starting your your HIV medicine.

HIV medicine.

COMPLERA, the COMPLERA Logo, EMTRIVA, GILEAD, the GILEAD Logo, GSI, HEPSERA, STRIBILD, TRUVADA, VIREAD, and VISTIDE are trademarks of Gilead Sciences, Inc., or its related companies.

ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other marks referenced herein are the property of their respective owners. ©2013 Gilead Sciences, Inc. All rights reserved. CPAC0056 09/13

The cost of

Living Assistance programs help pay for meds

HIV

Co-pay & Patient Assistance Programs

Drug

Company

Aptivus

Boehringer Ingelheim

Atripla

Bristol-Myers Squibb and Gilead Sciences

Combivir

ViiV Healthcare

Complera

Gilead Sciences and Janssen Therapeutics

Crixivan

Merck & Co.

Edurant

Janssen Therapeutics

Emtriva

Gilead Sciences

Epivir

ViiV Healthcare

Epzicom

ViiV Healthcare

Fuzeon Intelence

Genentech

Invirase Isentress

Genentech

Kaletra

AbbVie, Inc.

Lexiva

ViiV Healthcare

Norvir

AbbVie, Inc.

Prezista

Janssen Therapeutics

Rescriptor

ViiV Healthcare

Retrovir

ViiV Healthcare

Reyataz

Bristol-Myers Squibb

Selzentry

ViiV Healthcare

Stribild

Gilead Sciences

Sustiva

Bristol-Myers Squibb

Tivicay

ViiV Healthcare

Trizivir

ViiV Healthcare

Truvada

Gilead Sciences

Videx EC Viracept

Bristol-Myers Squibb

Viramune XR

Boehringer Ingelheim

Viread

Gilead Sciences

Zerit Ziagen

Bristol-Myers Squibb

By Jeff Berry and John Peller

T

reatment for HIV is expensive, but the good news is that help is out there! Several non-profit organizations and even the pharmaceutical companies themselves have programs to help you pay for the treatment you need.

Co-pay and Patient Assistance Programs

The Affordable Care Act

Most pharmaceutical companies provide some level of assistance through a patient assistance program (PAP) for people who can’t afford their HIV medications. These PAPs are typically for patients without insurance who don’t qualify for Medicare, Medicaid, or ADAP. Qualifications and criteria vary by program and are based on a percentage of Federal Poverty Level (FPL). Patients or providers should contact the program to see if they are eligible (see charts beginning on this page).

Many companies also have co-pay assistance programs for those who have drug coverage through privately held insurance. These programs may cover all or part of the drug co-pay up to a specified amount. Certain restrictions and eligibility requirements apply (for example, recipients of ADAP, Medicare, and Medicaid are not eligible). Individuals can get the co-pay card directly from their provider, the manufacturer’s website, or by calling a toll-free number. Some programs have a reimbursement process in case you are forced to pay the co-pay out of pocket if the pharmacy can’t or won’t accept the card. And some PAPs will make exceptions; for example, for a person on ADAP who has insurance but who has a high deductible, they may cover a certain percentage. Check with each program for details.

referred to as “Obamacare”) will improve access to coverage for many people with HIV. Although the new law is far from perfect, the ACA’s intention to provide more affordable benefits will allow many people with HIV to address their health needs.

Beginning this year, insurers won’t be able to deny coverage to people with HIV/AIDS or impose annual limits on coverage. Lowand middle-income earners may be eligible for tax subsidies to help them buy coverage from health insurance exchanges, or marketplaces. In 26 states that haven’t refused it (as of January 2014), Medicaid eligibility will expand to generally include those under 65 with incomes below 133% of the federal poverty level ($15,282 for an individual; $31,322 for a family of four).

Advocates across the country have raised concerns about the high cost of some HIV drugs available through some exchange plans. Although plans with affordable HIV drug coverage co-pays exist in almost all areas, individuals who select the wrong plan may have to pay $1,000 or more (up to 50%) in co-insurance for HIV drugs for several months out of the year. Make sure you know what your plan will cost in terms of co-insurance and deductibles, as well as the monthly premium. In addition, some plans do not cover all HIV medications. To make sure your drugs are included on the formulary of

82

The Affordable Care Act (ACA, commonly

March+April 2014 | positivelyaware.com/copay

Janssen Therapeutics

Merck & Co.

ViiV Healthcare

ViiV Healthcare

rograms (PAPs) Co-Pay Program

Patient Assistance

Details

None.

800-556-8317 rxhope.com or pparx.com

Patient assistance program only.

866-784-3431 atripla.com

866-290-4767 atripla.com

Co-pay program covers first $400 per month per prescription.

Card available through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online at mysupportcard.com or through provider.

877-505-6986 complera.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $400 per month per prescription.

Card available through your provider, AIDS service organization, and pharmacy.

None.

800-850-3430 merck.com/merckhelps

Patient assistance program only.

866-961-7169 edurant.com

800-652-6227 jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap.

Card available through your provider or at janssentherapeutics.com.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription.

Card available through your provider, AIDS service organization, and pharmacy.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through your provider.

None.

866-257-5084; fuzeon.com

Genentech Access to Care Foundation for un- and under-insured .

866-961-7169 intelence.com

800-652-6227 intelence.com, or jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap. Must re-apply annually. Card available through your provider or at janssentherapeutics.com.

None.

None.

No company programs.

866-350-9232 isentress.com

800-850-3430 isentress.com

Co-pay program covers up to $400 per month per prescription.

Card available online or through provider.

800-441-4987 kaletra.com

800-222-6885 kaletra.com, or abbviepaf.org

Co-pay program covers up to $200 per month per prescription. Must re-apply annually.

Card available online or through provider. 30-day sample program available.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider.

800-441-4987 norvir.com

800-222-6885 abbviepaf.org

Co-pay program covers up to $50 per month per prescription.

Card available through provider.

866-961-7169 prezista.com

800-652-6227 jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap.

Card available through your provider or at janssentherapeutics.com.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. For Retrovir only, not generic.

888-281-8981 reyataz.com

888-281-8981 bms.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider or by calling the toll-free number.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider.

877-585-6986 stribild.com

800-226-2056 stribild.com

Co-pay program covers up to $400 per month per prescription.

Card available through your provider.

888-281-8981 sustiva.com

888-281-8981 bms.com

Co-pay program covers up to $200 per month per prescription.

Card available through provider, or by calling toll-free number.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to 400 per month per prescription.

Card available online or through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription.

Card available through your provider, AIDS service organization, and pharmacy.

None.

bms.com

No company co-pay or patient assistance program for Videx. Available as generic.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available through your provider, AIDS service organization, and pharmacy.

877-411-8641 viramunexr.com

800-556-8317 needymeds.org

Co-pay program for Viramune XR only: Patient pays first $25; no cap. Card available through your provider. No co-pay or PAP for Viramune (IR); available as generic.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription.

Card available through provider.

None.

bms.com

No company co-pay or patient assistance program for Zerit. Available as generic.

866-747-1170 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription.

Card available online or through provider.

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83

the plan you choose; have a list of all your meds, for HIV and any other condition, and ask specifically if they are covered.

Fortunately, many state AIDS Drug Assistance Programs (ADAPs) can help pay out-of-pocket costs for HIV drugs obtained through some exchange plans.

ADAPs can also help pay premiums in some states. Check with your state ADAP to learn what your state offers, as well as the income limits. If you’re not eligible for ADAP, you may be able to use co-pay cards to make medications more affordable.

It is critical to consult a trained enrollment “navigator,” when choosing an exchange plan. Contact your local HIV/AIDS service organization for help or a referral.

Advocates are pressing for clarity from the administration as to whether or not qualified health plans (QHPs) purchased through a health insurance exchange are considered government programs, which would therefore make policyholders ineligible to receive co-pay assistance. As this issue went to press, several companies have interpreted it this way and are currently excluding people with QHPs from co-pay coverage.

Medicare Part D The Affordable Care Act provides for closing the Medicare Part D prescription drug benefit “donut hole” by 2020.

Beneficiaries receive a 50% discount on covered brand-name drugs while they are in the “donut hole,” with increased savings on prescription drugs while they are in the coverage gap until the gap is fully closed.

In addition, ADAP benefits are now considered as contributions toward Medicare Part D’s True Out of Pocket spending limit (“TrOOP”), so ADAP clients who have Medicare Part D should be able to benefit.

Harbor Path and the Common PAP Form HarborPath is a non-profit organization that helps uninsured people living with HIV/AIDS and/or hepatitis C to gain access to brand-name prescription medicines at no cost, by providing case managers with

a single online portal for PAP applications and medication fulfillment through a mailorder pharmacy. Go to harborpath.org.

The Department of Health and Human Services (DHHS), along with seven pharmaceutical companies, the National Alliance of State and Territorial AIDS Directors (NASTAD), and community stakeholders developed a common patient assistance program application that can be used by both providers and patients, instead of filling out different sets of paperwork for each company PAP. To download the form, go to hab.hrsa.gov/patientassistance.

Additional programs Co-pay and patient assistance programs are also available for hepatitis B and C drugs, and medications or treatments used for other HIV-related conditions such as lipodystrophy—some of these are included in the co-pay and PAP charts at right.

To learn more about patient assistance or co-pay programs for drugs used to treat certain opportunistic infections or other conditions, talk to your provider, contact the manufacturer directly, or go to pparx. org and needymeds.org. SurvivorRxPlan offers help in getting many medications not covered by ADAP, including alternative therapies and generics, even if you receive medicines through another discount program. It is available to individuals with incomes of up to $36,425, and higher based on family size. Go to SurvivorRxPlan.com.

Stay informed and up to date Keeping the lines of communication open between you and your health care provider, pharmacist, and case manager is essential when managing your health, so stay informed. Use the adjacent chart to check specific details, or go to positivelyaware. com/copay for the most current information, as details of specific programs may change.

Co-pay & Patient Assistance

Drug

Company

Baraclude

Bristol-Myers Squibb

Epivir-HBV Hepsera

ViiV Healthcare

Tyzeka

Novartis

Viread

Gilead Sciences

Hepatitis C Copegus ribavirin

Gilead Sciences

Co-pay & Patient Assistance Genentech

Incivek

Vertex Pharmaceuticals

Olysio

Janssen Pharmaceuticals

Pegasys

Genentech

PegIntron

Merck & Co.

Sovaldi

Gilead Sciences

Victrelis

Merck & Co.

peginterferon alfa-2a peginterferon alfa-2b

HIV-related conditions

Co-pay & Patient

Drug / ASSAY

Androgel (testosterone gel 1% & 1.62%) Used to treat adult males who have low or no testosterone.

Egrifta

Injectable approved for treating HIV-related excess belly fat (lipohypertrophy).

Fulyzaq

Anti-diarrheal approved for use in those with HIV/AIDS and on antiretroviral therapy.

HLA-Aware

HLA-B*5701 test to determine if a person can start taking Ziagen, Epzicom, or Trizivir.

Procrit

Treats anemia due to zidovudine therapy.

Radiesse

Injectable facial filler approved for use in people with HIV to treat facial fat loss (lipoatrophy).

Sculptra John Peller is Interim President/CEO

of AIDS Foundation of Chicago.

Special thanks to the Fair Pricing Coalition (FPC) for some of the information contained in this article. The FPC recently issued a policy guide which outlines issues and challenges that need to be addressed as people begin accessing care via Qualified Health Plans (QHPs) in the health insurance exchanges. Go to fairpricingcoalition.org.

[Note: Jeff Berry is a member of the FPC.]

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Hepatitis B

March+April 2014 | positivelyaware.com/copay

Injectable facial filler approved for use in people with HIV to treat facial fat loss (lipoatrophy).

Serostim

Injectable human growth hormone used for treating HIV-associated wasting in those on ART.

Testim (testosterone gel 1%) For adult males with low or no testosterone.

Trofile Assay

A test used for determining the tropism of a person’s HIV to identify if a CCR5 antagonist (such as Selzentry) would be effective.

Programs (PAPs) Co-Pay Program

Patient Assistance

Details

855-898-0267

855-898-0267 bmspaf.org

Co-pay program covers $200 per month, per prescription. Ask operator to speak to someone about the Baraclude Co-pay Discount Benefits Program, and have card mailed to you. Program runs through Dec. 31, 2014.

mysupportcard.com

866-475-3678; gskforyou.com

Co-pay program covers $200 per month, per prescription.

None.

800-226-2056 gilead.com/us_advancing_access

PAP only, no co-pay program.

None.

800-277-2254 pparx.org

PAP only, no co-pay program. PAP is through Novartis Patient Assistance Foundation, Inc.

877-627-0415

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers after first $50 and up to $200 per month for patients who are uninsured or pay their prescription costs in full.

888-941-3331 pegasysaccesssolutions.com

PAP only, no co-pay program.

855-837-8394 incivek.com

855-837-8394 incivek.com

Co-pay program covers co-pay costs up to $10,000 for those who have private insurance, regardless of income.

855-5-OLYSIO (65-9746) olysio.com

800-652-6227 jjpaf.org

Co-pay coupon program covers out of pocket costs to $25,000.

PAP is for those not qualified for other assistance up to 500% FPL.

866-422-2377 genetech-access.com

888-941-3331 pegasysaccesssolutions.com

Co-pay program through other non-profits.

866-939-4372 pegintron.com merck-cares.com

866-363-6379 merckhelps.com

Co-pay program covers up to $200 per month, per prescription.

855-769-7284

mysupportpath.com

Co-pay program covers up to $16,000, maximum $5 co-pay charge per prescription. PAP covers those not qualified for other assistance with a household income of up to $100,000 per year (1-3 people) and 500% FPL (4 or more).

866-939-4372; victrelis.com

866-363-6379 merckhelps.com

Co-pay program covers up to 20% of total cost of each Victrelis prescription up to 12 (44 weeks), including co-pays, co-insurance, or deductibles for those who have commercial insurance or are paying cash.

Programs (PAPs) None.

atient Assistance Programs (PAPs) Company

Co -Pay Program

Patient Assistance

Details

AbbVie, Inc.

800-441-4987 androgel.com

800-222-6885 abbviepaf.org; pparx.org

Co-pay: Patient pays first $10, then covers up to $50 per month. Card available through provider or you can print the card online.

EMD Serono

877-714-2947 egrifta.com

877-714-2947 egrifta.com

Co-pay program covers up to $500 of your co-pay or co-insurance per prescription. AXIS Center provides education and support; go to website or call 877-714-2947.

Salix Pharmaceuticals

800-508-0024 fulyzaq.com

800-933-8312 fulyzaq.com

Co-pay covers first use up to $100, then patient pays first $25 up to $100. Card available online or from provider. Support program helps with PAP, prior authorization and access issues.

LabCorp/ ViiV Healthcare

None.

800-533-1037 viivhcdxresource.com

No co-pay program, PAP only. Covers entire cost of test for insured/uninsured. Test must be ordered by provider.

Contact local ViiV rep, order online, or call.

Janssen

None.

800-652-6227 jjpaf.org

No co-pay program, PAP only.

Merz Aesthetics

None.

866-862-1211 radiesse-fl.com

No co-pay program. PAP is sliding scale based on patient’s annual income up to $80,000; reimbursement goes directly to physician.

Valeant Pharmaceuticals International

None.

866-310-7551 needymeds.org

No co-pay program. PAP provides two kits and one follow-up kit. Free for those with an annual income below $22,340, and then on a sliding scale up to $61,940.

EMD Serono

877-714-2947 serostim.com

877-714-2947 serostim.com

Co-pay program covers up to $200 of your co-pay or co-insurance per prescription discount, with a maximum of 12 prescription discounts per lifetime.

Auxilium

866-740-8252 testim.com

888-877-9192

Co-pay program covers up to $40 per month. Card available through provider or you can print the card online.

Monogram Biosciences

None.

877-436-6243 monogrambio.com viivhcdxresource.com

Gateway coverage for uninsured/underinsured; assists in prior authorization or if insurance reimbursement is denied.

ViiV also has Tropism Access Program (TAP) for ADAP eligible; see website, or contact state ADAP.

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85

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HIV/AIDS MEDICATION THERAPY But we also know you prefer pedaling over pumping gas.

Welcome to a pharmacy that gets to know you, not just your diagnosis. We’re not just treating HIV patients, we’re getting to know individuals.

So no matter the level of support, guidance and confidentiality you prefer, we’re here for you.

To learn more about our support services, visit HIV.Walgreens.com.

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