JAN+FEB 2011

Positively Aware January+February 2011

Hepatitis C

New, more effective therapies on the way

AGING & HIV

Who Would’ve THOUGHT we’d live this long?

DIVA ON STAGE One on One with Sheryl lee Ralph

COMPLICATIONS WHEN You’ve got more to balance than just HIV

The HIV Treatment & Health Journal of

Test Positive Aware Network

ABOUT PREZISTA

IMPORTANT SAFETY INFORMATION

What is the most important information I should Can PREZISTA be taken with other medications? know about PREZISTA? • Taking PREZISTA with certain • PREZISTA, together with Norvir ®, has medicines could cause serious and/ rarely been observed to cause liver or life-threatening side effects or may problems which may be life-threatening. result in loss of its effectiveness. Do PREZISTA is always taken with and at the same It was not always clear if PREZISTA not take PREZISTA if you are taking ® time as ritonavir (Norvir ), in combination with caused these liver problems because the following medicines: alfuzosin other HIV medicines for the treatment of HIV some patients had other illnesses or were (Uroxatral®), dihydroergotamine (D.H.E.45®, infection in adults. PREZISTA should also be taking other medicines. Your healthcare Migranal®), ergonovine, ergotamine taken with food. professional should do blood tests (Wigraine®, Ergostat ®, Cafergot ®, Ergomar ®), prior to starting combination treatment methylergonovine, cisapride (Propulsid®), • The use of other medicines active against including PREZISTA. If you have chronic pimozide (Orap®), oral midazolam, triazolam HIV in combination with PREZISTA/ritonavir hepatitis B or C infection, your healthcare (Halcion®), rifampin (Rifadin®, Rifater ®, (Norvir ®) may increase your ability to fight HIV. professional should check your blood tests Rifamate®), sildenafil (Revatio®) when used Your healthcare professional will work with more often because you have an increased to treat pulmonary arterial hypertension, you to find the right combination of chance of developing liver problems indinavir (Crixivan®), lopinavir/ritonavir HIV medicines (Kaletra®), saquinavir (Invirase®), lovastatin Talk to your healthcare professional about • It is important that you remain under the (Mevacor ®, Altoprev®, Advicor ®), pravastatin the signs and symptoms of liver problems. care of your healthcare professional during (Pravachol®), simvastatin (Zocor ®, Simcor ®, These may include yellowing of your treatment with PREZISTA Vytorin®), salmeterol (Serevent ®), or products skin or whites of your eyes, dark (teacontaining St. John’s wort PREZISTA does not cure HIV infection or colored) urine, pale-colored stools (bowel • Before taking PREZISTA, tell your healthcare AIDS, and does not prevent passing HIV movements), nausea, vomiting, loss of professional if you are taking sildenafil to others. appetite, or pain, aching or sensitivity on (Viagra®), vardenafil (Levitra®), tadalafil your right side below your ribs (Cialis®, Adcirca®), atorvastatin (Lipitor ®), • Skin rashes have been reported in patients atorvastatin/amlodipine (Caduet ®), taking PREZISTA. Rarely, PREZISTA has rosuvastatin (Crestor ®), or colchicine been reported to cause a severe or life(Colcrys®). This is not a complete list of threatening rash. Contact your healthcare medicines. Be sure to tell your healthcare professional immediately if you develop a professional about all the medicines rash. Your healthcare professional will advise you are taking or plan to take, including you whether your symptoms can be managed prescription and nonprescription on therapy or whether PREZISTA should medicines, vitamins, and herbal be stopped supplements PREZISTA® (darunavir) is a prescription medicine. It is one treatment option in the class of HIV (human immunodeficiency virus) medicines known as protease inhibitors.

Belief {

in myself in my doctor in my meds

ONCE-DAILY PREZISTA FOR ADULTS TAKING HIV MEDS FOR THE FIRST TIME In a clinical study* of almost 2 years (96 weeks) in people who had never taken HIV meds before, ONCE-DAILY PREZISTA with low-dose ritonavir plus Truvada®…

• Helped 8 out of 10 people achieve undetectable viral load (less than 50 copies/mL) • May help to increase T-cell count • Was associated with low rates of diarrhea, stomach pain, nausea, and vomiting — Diarrhea (8%), stomach pain (5%), nausea (3%), and vomiting (2%) were reported as moderate to severe PREZISTA must be taken with and at the same time as 100 mg of Norvir® (ritonavir), and with other HIV meds and with food.

Once-daily dosing of PREZISTA is not recommended for adults who have taken HIV meds in the past.

Please read Important Safety Information below and ask your doctor if once-daily PREZISTA is right for you.

Individual results may vary.

What are the possible side effects of PREZISTA? • Tell your healthcare professional if you are taking estrogen-based contraceptives • High blood sugar, diabetes or worsening of (birth control). PREZISTA might reduce diabetes, and increased bleeding in people the effectiveness of estrogen-based with hemophilia have been reported in patients contraceptives. You must take additional taking protease inhibitor medicines, precautions for birth control, such as condoms including PREZISTA • Changes in body fat have been seen in some What should I tell my doctor before I take patients taking HIV medicines, including PREZISTA? PREZISTA. The cause and long-term health • Before taking PREZISTA, tell your healthcare effects of these conditions are not known at professional if you have any medical conditions, including allergy to sulfa medicines, this time diabetes, liver problems (including hepatitis B • As with other protease inhibitors, taking or C), or hemophilia PREZISTA may strengthen the body’s immune response, enabling it to begin to fight infections • Tell your healthcare professional if you are that have been hidden. Patients may experience pregnant or planning to become pregnant, or signs and symptoms of inflammation that can are breastfeeding include swelling, tenderness, or redness – The effects of PREZISTA on pregnant women • The most common side effects related to or their unborn babies are not known. You taking PREZISTA include diarrhea, nausea, and your healthcare professional will need to rash, headache, stomach pain, and vomiting. decide if taking PREZISTA is right for you Uncommon but severe side effects such as – Do not breastfeed if you are taking PREZISTA. inflammation of the pancreas and increased You should not breastfeed if you have HIV blood fat levels have also been rarely reported. because of the chance of passing HIV to This is not a complete list of all possible side your baby 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 Distributed by: Tibotec Therapeutics/Division of Centocor Ortho Biotech Products, L.P. Titusville, NJ 08560 ©2010 Tibotec Therapeutics 05/10 28PRZDTC0010AR3 All trademarks are property of their respective owners.

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

• For adults taking HIV meds for the first time: PREZISTA 800 mg (two 400-mg tablets) must be taken at the same time with 100 mg Norvir ® once daily every day. PREZISTA must be taken with food Please see Important Patient Information on the next page for more information, or visit www.PREZISTA.com.

If you or someone you know needs help paying for medicine, call 1-888-4PPA-NOW (1-888-477-2669) or go to www.pparx.org. *343 adult patients (30% women) received combination therapy with PREZISTA/ritonavir. At the start of the study, the average T-cell count was 245, and 66% of patients had a viral load less than 100,000 copies/mL.

ONCE DAILY www.PREZISTA.com/patient

IMPORTANT PATIENT INFORMATION PREZISTA® (pre-ZIS-ta) [(darunavir) (da-ROO-nuh-veer)] Tablets ALERT: Find out about medicines that should NOT be taken with PREZISTA. Please also read the section “Who should not take PREZISTA?”.

Please read this information before you start taking PREZISTA. Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss your treatment with PREZISTA prior to the first time you take your medicine and at regular checkups. You should remain under a doctor’s care when using PREZISTA and should not change or stop treatment without first talking with a doctor.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT PREZISTA? PREZISTA, together with NORVIR® (ritonavir), has rarely been observed to cause liver problems which may be life-threatening. It was not always clear if PREZISTA caused these liver problems because some patients had other illnesses or were taking other medicines. Your healthcare professional should do blood tests prior to initiating combination treatment including 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. Please also read the section “What are the possible side effects of PREZISTA?”.

Rarely, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash.

Your healthcare provider will advise you whether your symptoms can be managed on therapy or whether PREZISTA should be stopped.

WHAT IS PREZISTA? PREZISTA is an oral tablet used for the treatment of HIV (Human Immunodeficiency Virus) infection in adults. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). PREZISTA is a type of anti-HIV medicine called a protease (PRO-tee-ase) inhibitor.

HOW DOES PREZISTA WORK? PREZISTA blocks HIV protease, an enzyme which is needed for HIV to multiply. When used with other anti-HIV medicines, PREZISTA can help to reduce the amount of HIV in your blood (called “viral load”) and increase your CD4 (T) cell count. HIV infection destroys CD4 (T) cells, which are important to the immune system. The immune system helps fight infection. Reducing the amount of HIV and increasing the CD4 (T) cell count may improve your immune system and, thus, reduce the risk of death or infections that can happen when your immune system is weak (opportunistic infections).

PREZISTA is always taken with and at the same time as ritonavir (NORVIR®), in combination with other anti-HIV medicines. PREZISTA should also be taken with food.

DOES PREZISTA CURE HIV OR AIDS? PREZISTA does not cure HIV infection or AIDS. At present, there is no cure for HIV infection. People taking PREZISTA may still develop infections or other conditions associated with HIV infection. Because of this, it is very important for you to remain under the care of a doctor. Although PREZISTA is not a cure for HIV or AIDS, PREZISTA can help reduce your risks of getting illnesses associated with HIV infection (AIDS and opportunistic infection) and eventually dying from these conditions.

DOES PREZISTA REDUCE THE RISK OF PASSING HIV TO OTHERS? PREZISTA does not reduce the risk of passing HIV to others through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safer sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood. Never re-use or share needles.

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

WHAT SHOULD I TELL MY DOCTOR BEFORE I TAKE PREZISTA? Tell your doctor about all of your medical conditions, including if you: • are allergic to sulfa medicines.

• have diabetes. In general, anti-HIV medicines, such as PREZISTA, might increase sugar levels in the blood.

• have liver problems, including hepatitis B and/or C. • have hemophilia. Anti-HIV medicines, such as PREZISTA, might increase the risk of bleeding.

• are pregnant or planning to become pregnant. The effects of PREZISTA on pregnant women or their unborn babies are not known. You and your doctor will need to decide if taking PREZISTA is right for you. If you take PREZISTA while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry.

• are breastfeeding. Do not breastfeed if you are taking PREZISTA. You should not breastfeed if you have HIV because of the chance of passing HIV to your baby. Talk with your doctor about the best way to feed your baby.

WHO SHOULD NOT TAKE PREZISTA?** Together with your doctor, you need to decide whether taking PREZISTA is right for you.

Do not take PREZISTA if you: • are allergic to darunavir or any of the other ingredients in PREZISTA • are allergic to ritonavir (NORVIR®) • take any of the following types of medicines because you could experience serious side effects: – alfuzosin (Uroxatral®) – dihydroergotamine (D.H.E. 45®, Migranal®), ergonovine, ergotamine (Cafergot®, Ergomar®), methylergonovine – cisapride – pimozide (Orap®) – oral midazolam, triazolam (Halcion®) – 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 CAN PREZISTA BE TAKEN WITH OTHER MEDICATIONS?** Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. PREZISTA and many other medicines can interact. Sometimes serious side effects will happen if PREZISTA is taken with certain other medicines (see “Who should not take PREZISTA?”).

Tell your doctor 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 a condom.

Tell your doctor if you take other anti-HIV medicines. PREZISTA can be combined with some other anti-HIV medicines while other combinations are not recommended.

Tell your doctor if you are taking any of the following medicines: – bepridil, lidocaine, quinidine, amiodarone (Cordarone®), digoxin (Lanoxin®), flecainide (Tambocor®), propafenone (Rythmol®), – warfarin (Coumadin®) – carbamazepine (Tegretol®, Carbatrol®), phenobarbital, phenytoin (Dilantin®, Phenytek®) – trazodone (Desyrel®), desipramine (Norpramin®) – colchicine (Colcrys®) – clarithromycin (Biaxin®) – ketoconazole (Nizoral®), itraconazole (Sporanox®), voriconazole (Vfend®) – rifabutin (Mycobutin®) – metoprolol (Lopressor®, Toprol-XL®), timolol (Betimol®, Combigan®, Istalol®, Cosopt®, Timoptic®) – midazolam administered by injection – felodipine (Plendil®), nifedipine (Adalat®), nicardipine (Cardene®) – dexamethasone, fluticasone (Advair Diskus®, Cutivate®, Flonase®, Flovent Diskus®) – bosentan (Tracleer®) – atorvastatin (Lipitor®), pravastatin (Pravachol®), rosuvastatin (Crestor®) – cyclosporine (Sandimmune®, Neoral®), tacrolimus (Prograf®), sirolimus (Rapamune®)

IMPORTANT PATIENT INFORMATION – salmeterol (Serevent®) – methadone, buprenorphine/naloxone – risperidone (Risperdal®, Risperdal® Consta®,Risperdal® M-TAB®), thioridazine – sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®) – tadalafil (Adcirca®) – paroxetine (Paxil®), sertraline (Zoloft®) Tell your doctor if you are taking any medicines that you obtained without a prescription.

This is not a complete list of medicines that you should tell your doctor that you are taking. Know and keep track of all the medicines you take and have a list of them with you. Show this list to all of your doctors and pharmacists any time you get a new medicine. Both your doctor and your pharmacist can tell you if you can take these other medicines with PREZISTA. Do not start any new medicines while you are taking PREZISTA without first talking with your doctor or pharmacist. You can ask your doctor or pharmacist for a list of medicines that can interact with PREZISTA. HOW SHOULD I TAKE PREZISTA? Take PREZISTA tablets every day exactly as prescribed by your doctor. You must take ritonavir (NORVIR®) at the same time as PREZISTA. • For adults who have never taken anti-HIV medicines, the usual dose is 800 mg (two 400 mg tablets) of PREZISTA, together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR®), once daily every day.

• For adults who have taken anti-HIV medicines in the past, the usual dose is 600 mg (one 600 mg tablet or two 300 mg tablets) of PREZISTA, together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR®), twice daily every day. Do not take PREZISTA once daily if you have taken anti-HIV medicines in the past.

PREZISTA and ritonavir (NORVIR®) should be taken together at the same time every day. If you have questions about when to take PREZISTA and ritonavir (NORVIR®), your doctor can help you decide which schedule works for you.

Take PREZISTA and ritonavir (NORVIR®) with food. Swallow the whole tablets with a drink such as water or milk. Do not chew the tablets.

Continue taking PREZISTA and ritonavir (NORVIR®) unless your doctor tells you to stop. Take the exact amount of PREZISTA and ritonavir (NORVIR®) that your doctor tells you to take, right from the very start. To help make sure you will benefit from PREZISTA and ritonavir (NORVIR®), you must not skip doses or interrupt therapy. If you don’t take PREZISTA and ritonavir (NORVIR®) as prescribed, the beneficial effects of PREZISTA and ritonavir (NORVIR®) may be reduced or even lost.

Patients taking PREZISTA once daily If you miss a dose of PREZISTA or ritonavir (NORVIR®) by more than 12 hours, wait and then take the next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time. If you miss a dose of PREZISTA or ritonavir (NORVIR®) by less than 12 hours, take your missed dose of PREZISTA and ritonavir (NORVIR®) immediately. Then take your next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time.

Patients taking PREZISTA twice daily If you miss a dose of PREZISTA or ritonavir (NORVIR®) by more than 6 hours, wait and then take the next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time. If you miss a dose of PREZISTA or ritonavir (NORVIR®) by less than 6 hours, take your missed dose of PREZISTA and ritonavir (NORVIR®) immediately. Then take your next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time.

You should always take PREZISTA and ritonavir (NORVIR®) together with food.

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

WHAT ARE THE POSSIBLE SIDE EFFECTS OF PREZISTA? Like all prescription drugs, PREZISTA can cause side effects. The following is not a complete list of side effects reported with PREZISTA when taken either alone or with other anti-HIV medicines. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects.

PREZISTA, together with NORVIR® (ritonavir), has rarely been observed to cause liver problems which may be life-threatening. It was not always clear if PREZISTA caused these liver problems because some patients had other illnesses or were taking other medicines. Your healthcare professional should do blood tests prior to initiating combination treatment including 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.

Talk to your healthcare professional about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea colored) urine, pale colored stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching or sensitivity on your right side below your ribs.

Rash has been reported in 10.3% of patients receiving PREZISTA. In few patients, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash.

Your healthcare provider will advise you whether your symptoms can be managed on therapy or whether PREZISTA should be stopped.

Other relevant severe side effects reported at an uncommon or rare frequency were inflammation of the liver or pancreas, increased blood fat levels, diabetes, and changes in body fat.

Some side effects are typical for anti-HIV medicines in the same family as PREZISTA. These are: • high blood sugar (hyperglycemia) and diabetes. This can happen in patients taking PREZISTA or other protease inhibitor medicines. Some patients have diabetes before starting treatment with PREZISTA which gets worse. Some patients get diabetes during treatment with PREZISTA. Some patients will need changes in their diabetes medicine. Some patients may need new diabetes medicine.

• increased bleeding in patients with hemophilia.

• changes in body fat. These changes can happen in patients taking anti-HIV medicines, including PREZISTA. The changes may include an increased amount of fat in the upper back and neck, 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 long-term health effects of these conditions are not known.

• immune reconstitution syndrome. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment, including PREZISTA, is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms.

The most common side effects include diarrhea, nausea, rash, headache, abdominal pain and vomiting.

Tell your doctor promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.

This medication is prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep PREZISTA and all of your medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control center or emergency room immediately.

This is a brief summary of information about PREZISTA for adult patients with HIV. If you have any questions or concerns about either PREZISTA or HIV, talk to your doctor.

For additional information, you may also call Tibotec Therapeutics at 1-877-REACH-TT or 1-877-732-2488. **The brands listed are the registered trademarks of their respective owners and are not trademarks of Tibotec Pharmaceuticals, Ltd.

Manufactured for Tibotec, Inc. by: JOLLC, Gurabo, Puerto Rico Distributed by: Tibotec Therapeutics, Division of Centocor Ortho Biotech Products, L.P., Raritan NJ 08869 Patent Numbers: 5,843,946; 6,248,775; 6,335,460 and other US patents pending NORVIR® is a registered trademark of its respective owner.

PREZISTA® is a registered trademark of Tibotec Pharmaceuticals, Ltd.

© Tibotec, Inc. 2006

Revised: April 2010

10101711P

January+February 2011 VOLUME 23 | NUMBER 1

D e pa r t m e n t s

F e at u r e s

Editor’s Note

Hepatitis C drugs in the pipeline

HIV—it’s complicated.

7

In Box PA Reader poll

8

New, more effective therapies are on the way—and will be well worth the wait.

15

Conference report

Briefly Lipodystrophy treatment approved.

Gardasil protects against anal cancer. Another three-in-one pill on the way. Truvada cuts HIV risk.

10

HIV-related inflammation. Switching to Truvada or Epzicom can stop fat loss, study confirms. Vitamin D deficiency.

20

Point of origin

Positive about getting a flu shot.

A look at the discovery and spread of HIV.

HIV Wellness Series

Bones of contention

Ask the HIV specialist

19

Aging and HIV: Who would have ever thought we’d live this long?

25

The Buzz Egrifta gains FDA approval, while testosterone remains tried and true.

34

22

Premature aging and bone loss emerge as new concerns with HIV.

28

Getting down with the diva

Sheryl Lee Ralph discusses Divas Simply Singing and her work on the AIDS front.

30 Wholistic picture Ode to control freaks.

37

On the Cover and on this page: Model: Yunzuo Cai | Photo by Chris Knight

P o s i t i v e lyAwa r e . c o m

J a n u a r y + F e b r u a r y 2 0 1 1 | 5

SAVE THE DATE

USCA 2011 CHIC AGO

NOVEMBER 10-13

Positively Aware 5537 N. Broadway St. Chicago, IL 60640 phone: (773) 989–9400 | fax: (773) 989–9494 e- mail: publications@tpan.com | www.PositivelyAware.com E d it o r i a l

editor

associate editor

editorial assistant

proofreaders

contributing writers

contributing photographers

art director

Jeff Berry Enid Vázquez Sue Saltmarsh Jason Lancaster, David Perez Keith R. Green, Liz Highleyman, Sal Iacopelli, Laura Jones, Jim Pickett, Matt Sharp Chris Knight, Joshua Thorne Rick Guasco artdirector@tpan.com

M e d i c a l a d vi s o r y b o a r d Daniel S. Berger, MD; Gary Bucher, MD; Michael Cristafano, PA; Joel Gallant, MD; Swarup Mehta, PharmD

A d v e r ti s i n g & Di s t r i b u ti o n

advertising inquiries

distribution

Jessie Mott j.mott@tpan.com Billy Surber distribution@tpan.com

Positively Aware is published bi-monthly by Test Positive Aware Network. © 2011. Positively Aware (ISSN: 1523-2883) is published bi-monthly by Test Positive Aware Network (TPAN), 5537 N. Broadway St, 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: 85,000. For reprint permission, contact Sue Saltmarsh. Six issues mailed bulk rate for $30 donation; mailed free to TPAN members or those unable to contribute.

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

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 Aware are not necessarily those of staff or membership 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, membership in TPAN, or contributions to this journal.

Distribution of Positively Aware is supported in part through an unrestricted grant from Viiv Healthcare.

6 | Ja nua ry+Februa ry

2011

P os i t i v e lyAwa r e .co m

Editor’s Note Jeff Berry

HIV—it’s complicated

PHOTO: Chris Knight

I tested positive in September of 1989 and I was devastated. There I was at the tender, young age of 30, at my virtual peak, and I had lost more friends to AIDS than I cared to count or could even recall. I wasn’t sure how much time I had left on this earth myself. It was a scary time—and this was still seven years before the era of protease inhibitors and the advent of HAART, so I had a right to be scared. We all did.

But then things slowly started to change.

The drugs that were being developed and brought to market began to be more effective than their predecessors at reducing viral load and restoring the immune system, albeit still with some pretty nasty side effects. Diarrhea, kidney stones, anemia— you name it, it wasn’t pretty.

Since then we’ve come a long way in the treatment of HIV and AIDS. We’ve been able to get down to as few as one or two pills, once or twice a day, with great results and fewer and fewer side effects. If diagnosed and treated early enough, many people can expect to live for years, even decades, with what some are now referring to as a lifelong chronic, manageable condition.

However, there are still many complications associated with HIV and AIDS, as well as long-term side effects of HIV treatment, including diseases and complications of the liver, bones, kidneys, and heart, and brain impairment or dementia. People with HIV are also more prone to certain cancers, including Kaposi’s sarcoma, lymphoma, and cervical cancer. In addition, aging and metabolic issues, including lipodystrophy (body fat redistribution) and diabetes can affect not only your physical but your mental health as well.

P o s i t i v e lyAwa r e . c o m

I was only in my forties when I had to begin taking medication to lower my cholesterol and keep my blood pressure under control. Friends of mine who were the same age—and even younger—had to have their hips replaced and already had heart surgery—twice. The fat is being sucked right out of our cheeks and pumped into our bellies. I feel like the six-million dollar man desperately in need of a bailout, and that’s on a good day. Just call me Frankenpoz the rest of the time.

HIV is definitely complicated.

This is not to scare anyone from seeking help. As studies have shown, the earlier we get tested, into care, and onto treatment, the better for everyone in the long run. Improved survival, better response to the drugs, reduction in community viral load—hey, what’s not to like?

Let’s face it, the ARV drugs available today are much better now than they were 15, 10, even 5 years ago. And more are in the pipeline and coming soon.

But it’s still no walk in the park. The longer we live, the more things can go wrong with us. Makes sense, I guess. Having complications which may be a result of the medications themselves can also adversely affect adherence, which can ultimately lead

to resistance, so it’s important to be able to minimize these side effects whenever possible. Talk to your doctor, watch your diet, exercise regularly, and make sure you get enough rest. And not to get too preachy, but remember that the number one health hazard to people with HIV is smoking, so if possible, try to cut down, or even better yet—quit altogether!

I hear many docs who are saying that the drugs we have now are working just fine, so why change anything? As the saying goes, if it ain’t broke, don’t fix it. But now is not the time to rest on our AZT-wasted laurels, especially when it comes to HIV. Otherwise, in a few years we’ll find ourselves right back where we started, with no effective treatments available and none in the foreseeable future. Some of us who’ve developed multi-drug resistance have unfortunately already reached that point.

That is why it’s more important than ever that we continue to invest in drug development that explores novel targets and once-weekly or monthly dosing, and increase funding into viral eradication and cure research, vaccine development, and HIV and aging. We also need to keep plugging away at pre-exposure prophylaxis— we’re definitely on a roll, and we need to keep the momentum going. The more we do to chip away at the current state of affairs that we find ourselves in, the less scary and complicated it becomes—for all of us.

Take care of yourself, and each other.

J a n u a r y + F e b r u a r y 2 0 1 1 | 7

In Box

Positivelyaware.com

To each his own

Last issue’s poll question:

In the September/October 2010 issue, Mary Beth Alder answers the question about differences between physicians and nurse practitioners in the care of HIV patients [see Ask the HIV Specialist]. As a physician who takes care of HIV patients, I do agree that nurse practitioners are essential in providing quality medical care to a growing population of HIV patients in the U.S. In fact, many HIV-practicing physicians today will be retiring in the next 10 years, and as a result, more patients will seek care from mid-level providers.

However, I have concerns with some of her comments. Ms. Alder wrote that “nurse practitioners can often provide the same level of medical care as an MD.” Yes, they can provide similar care to patients, but given the educational and training requirements to be a physician, it may be very difficult to accept her statement when it comes to managing complex medical diagnoses and treatment plans for some of our complicated patients. For example, it would be more ideal for a highly treatment-experienced AIDS patient who takes novel agents and multiple medications for opportunistic infections and depression to seek advice and care from an experienced physician trained in HIV medicine.

It is also my recommendation that nurse practitioners who are faced with similar, complicated cases seek consultation from their physician counterparts for improved patient care.

In addition, I am somewhat displeased with Ms. Alders’ comment that “the nursing scope of practice differs somewhat from the medical scope of practice in that it centers around a holistic approach to patient care.” She implies that the medical scope of physician practice does not include holistic values. As an osteopathic physician (DO degree), a holistic approach 8 | J a n u a r y + F e b r u a r y

2011

to medicine and patient care is incorporated into my daily practice. According to the osteopathic philosophy, a greater emphasis is placed on primary care and holistic health in the combination of body, mind, and spirit. It also recognizes that educational, social, and psychological factors can affect patient care.

Physicians, as well, are able to practice more patient-centered and holistic care.

Hopefully, your readers can have a deeper understanding that physicians and nurse practitioners have similar and different ways of practicing medicine. No two individual providers practice the same kind of medicine. Patients need to choose which provider is right for them.

—Jon Persichino, DO, AAHIVM Moreno, CA

A Day with HIV in America I went to www.adaywithhivinamerica.com and looked through the galleries. They’re awesome! A great site!

So happy to have been a part.

Many thanks, —Bradford McIntyre Vancouver, British Columbia Thanks for using my photo in the feature, I’m really proud to be included in such an important piece of work. Living with HIV isn’t easy, so to see my photo and name like that is quite moving and liberating.

That’s why I wanted to drop you a line to say thank you. You really have made me feel part of something worthwhile and valued!

—Martin Cambridge, UK

Have you, or has anyone you know, ever taken PEP or PrEP?

YES: 20%

NO: 80%

this issue’s poll question:

Have you ever experienced any complications from HIV or HIV meds? cast your vote at

positivelyaware.com Follow us on Facebook and Twitter

Introducing

The Digital Edition of Positively Aware.

It’s a new way to read—and utilize—Positively Aware, the nation’s leading HIV treatment journal. Now you can read the print version of Positively Aware from your computer. More than that, you can print articles, e-mail them to friends, post them online, or share them with your friends on Facebook and Twitter.

Go to www.PositivelyAware.com and click on “View the Digital Edition of Positively Aware.”

Or, go directly to www.Issuu.com/PositivelyAware P o s i t i v e lyAwa r e . c o m

Briefly reported by enid Vázquez

On November 10, the U.S. Food and Drug Administration (FDA) approved Egrifta (generic name tesamorelin), a once-daily injection for the treatment of lipodystrophy in HIV-positive people (see The Buzz on p. 34). Lipodystrophy is a condition which includes abnormalities in body fat distribution and metabolism, and is associated with many HIV drugs. The greatest concern is visceral fat, the layer that sits on the liver, stomach, and other abdominal organs, because there is a direct correlation with increased risk of developing heart disease, high blood pressure, diabetes, sleep apnea, stroke, certain types of cancer, and other diseases. Moreover, it decreases quality of life and has been known to keep people from starting HIV therapy, or to cause them to stop taking it. Egrifta is the first FDA approved treatment for lipodystrophy. According to an FDA press release, “Egrifta was evaluated in two clinical trials involving 816 HIVinfected adult men and women with lipodystrophy and excess abdominal fat. Of these, 543 patients received Egrifta during a 26-week, placebo-controlled period. In both studies, patients treated with Egrifta experienced greater reductions in abdominal fat (15-17%) as measured by CT scan, compared with patients receiving another, non-active injectable solution (placebo).

Some patients reported improvements in their self image.” Prescriptions must

be filed with EMD Serono’s Axis program (877-714-2947) and will be handled by select mail-order pharmacies. The Axis program will assume responsibility for seeking reimbursement for the drug, working directly with insurance companies and prescribers. EMD Serono, which is marketing the drug in the U.S., will also have a co-pay program to help cover drug co-pays for those with insurance, and a patient assistance program (PAP) for those who are underinsured or without insurance. Visit www.emdserono.com or www.egrifta.com.

Another threein-one HIV pill In November, Gilead Sciences submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for a combination of its Truvada medicine and TMC278, an experimental HIV non-nucleoside analogue (the same class of medication as Sustiva), from Tibotec Pharmaceuticals.

Expected to be approved in 2011, the new medication is the second HIV treatment that provides an entire regimen in one pill. The popular Atripla, consisting of Truvada and Sustiva, was the first.

Paying less for Isentress In October, Merck announced an enhanced co-pay assistance program for its HIV drug Isentress. The program removes the previously required $30 co-pay and is good for outof-pocket costs up to $400, making this the most generous co-pay assistance program out there for an HIV drug. The program is for privately insured individuals with outof-pocket co-pays. HIV treatment advocates from the Fair Pricing Coalition, including Positively Aware editor Jeff Berry, have been working with pharmaceutical companies to alleviate the financial pressures of antiretroviral therapy (see the Annual HIV Drug Guide in Positively Aware’s March/April issue). For more information, call 1-877-264-2440 or visit www.Isentress.com.

10 | J a n u a r y + F e b r u a r y

2011

Gardasil protects against anal cancer As Positively Aware went to press in December, the U.S. Food and Drug Administration (FDA) was set to approve a new use (indication) for the Gardasil vaccine. Gardasil is a vaccine that protects men and women from four kinds of human papillomavirus (HPV).

HPV can cause genital and other warts in both men and women and cervical cancer in women. In November, an FDA advisory committee determined that data on Gardasil support its approval for the prevention of anal cancer and anal intraepithelial neoplasia (AIN, a precursor to cancer) in both males and females.

Principle investigator Joel Palefsky, MD, of the University of California, San Francisco, is a leader in the research and treatment of anal cancer, particularly in the high-risk population of men who have sex with men (MSM), as well as people with HIV. There is no contraindication against Gardasil for HIV-positive people, he told Positively Aware. Furthermore, he said, “I strongly believe we should be doing a better job of educating MSM, whether positive or negative, to get vaccinated as early as possible.” A big question will be answered later this year, he noted, when a decision is made on whether to recommend Gardasil for protection against anal cancer and disease by the Advisory Committee for Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC). Insurance reimbursement and government payment for Gardasil rests on the strength of an ACIP recommendation.

The data reviewed were from a study of MSM, and were related to use of the vaccine in both men and women because anal cancer affects both sexes and the disease is similar in both.

P o s i t i v e lyAwa r e . c o m

Photo: VÁzquez: JOSHUA THORNE

Lipodystrophy treatment approved

Sign up for weekly e-NEWS, go to PositivelyAware.com

Microbicide gel hits the fast track There’s good news for HIV prevention.

The vaginal gel which the CAPRISA 004 study (see the September/October issue of Positively Aware) showed was able to significantly cut the risk of HIV has been put on the fast track to approval by the U.S. Food and Drug Administration (FDA). In a meeting on October 20, the FDA agreed to give the gel, a formula containing 1% of the HIV medication tenofovir (brand name Viread, which is also contained in the antivirals Truvada and Atripla), a Fast Track approval designation. This means that the agency will consider study findings as they are completed, rather than waiting for all results to be finished. The agency designated another study from the Microbicide Trials Network, or MTN, called VOICE (Vaginal and Oral Interventions to Control the Epidemic), also known as MTN-003, as all that is needed for approval if results confirm those of the South African trial.

Unlike the CAPRISA study, however, in which women used tenofovir gel up to 12 hours before and up to 12 hours after sex, VOICE looks at daily use of the microbicidal gel. It is also studying daily oral use of tenofovir tablets in addition to the gel (in separate arms of the trial).

Invirase update The U.S. Food and Drug Administration (FDA) in October added a warning to the drug label for the HIV medication Invirase, which is always taken with a booster dose of another HIV drug, Norvir.

According to the FDA, there is a potential for change in the electrical activity of the heart when Invirase/Norvir is used, which may lead to abnormal heart rhythms.

Patients should not stop taking Invirase before first consulting their doctor, the FDA advises.

P o s i t i v e lyAwa r e . c o m

iPrEx study: Truvada cuts HIV risk The anti-HIV combo drug Truvada (tenofovir/emtricitabine, or TDF/FTC) was shown to actually cut the risk of acquiring HIV in people at high risk of infection who took the pill every day. Overall, there was a 44% reduction in the risk of becoming infected with HIV, but a 73% reduction for those people who took the daily pill 90% of the time, according to a study called iPrEx, published in the November 23rd issue of the New England Journal of Medicine. This is the first time that the HIV prevention strategy called pre-exposure prophylaxis (prevention), or PrEP, provided evidence of effectiveness in humans during a study. “The iPrEx study proves that PrEP provides important additional protection against HIV when offered with other prevention methods such as HIV testing, counseling, condom use, and management of sexually transmitted infections,” said iPrEx protocol chair Robert Grant, MD, MPH in a press release. “As with other prevention methods, the greatest protection comes with consistent use. I hope this finding inspires a renewed commitment from communities, industry, and government to stop the spread of HIV.” Grant is with the Gladstone Institutes and the University of California, San Francisco. The iPrEx results are from 2,499 men and transgender women who were born men, all of whom have sex with men and 40% of whom had exchanged sex for money. In addition to counseling for safer sex practices and medication adherence, plus condoms and regular HIV testing, half of the participants were given Truvada and the other half received a placebo (fake pill). There were 36 infections in the Truvada group vs. 64 infections in the placebo group. The study took place at 11 sites in Brazil, Ecuador, Peru, South Africa, Thailand, and the United States. It was funded by the U.S. National Institutes of Health (NIH), with additional support from the Bill & Melinda Gates Foundation.

Once-daily Isentress study stopped Alas. A study found that a once-daily dose of Isentress did not do as well as the FDA approved twice-daily dose. Although the experimental once-daily dose got 83.2% (318/382) of study participants taking it down to an undetectable HIV viral load of less than 50 copies at 48 weeks, it was not shown to be non-inferior to the twicedaily dose, manufacturer Merck reported in November. That compares to 88.9% of participants (343/386) on the twice-daily dose who achieved undetectable viral load.

The study was stopped and the company recommended that people on the oncedaily dose be switched to twice-daily dosing. The company said the difference was driven by people with high viral loads of more than 100,000. Of the once-daily participants, 74.3% (113/152) had undetectable viral loads vs. 84.2% (129/152) of the twice-daily group. Safety and tolerability was the same for the two groups. Study participants were taking HIV medicine for the first time.

ONLY At POSITIVELYAWARE.COM Navigating the challenge of living with diabetes when you’re already HIV-positive. Read “Double Whammy,” an online exclusive.

J a n u a r y + F e b r u a r y 2 0 1 1 | 11

• EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in adults.

• EPZICOM is one of 3 medicines containing abacavir.

Before starting EPZICOM, your healthcare provider will review your medical history in order to avoid the use of abacavir if you have experienced an allergic reaction to abacavir in the past.

• In one study, more patients had a severe hypersensitivity reaction in the abacavir once-daily group than in the abacavir twice-daily group.

• EPZICOM should not be used as part of a triple-nucleoside regimen.

• EPZICOM does not cure HIV infection/AIDS or prevent passing HIV to others.

Important Safety Information EPZICOM contains abacavir, which is also contained in ZIAGEN® (abacavir sulfate) and TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine). Patients taking abacavir may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not.

Your healthcare provider can determine with a blood test if you have this gene variation. If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your doctor right away to determine if you should stop taking this medicine.

1. Fever 2. Rash 3. Nausea, vomiting, diarrhea, or abdominal (stomach area) pain 4. Generally ill feeling, extreme tiredness, or achiness 5. Shortness of breath, cough, or sore throat Carefully read the Warning Card that your pharmacist gives you and carry it with you at all times.

If you stop EPZICOM because of an allergic reaction, NEVER take EPZICOM or any other abacavir-containing medicine (ZIAGEN, TRIZIVIR) again. If you take EPZICOM or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

I’ve got the fight in me.

If you stop EPZICOM for any other reason, even for a few days, and you are not allergic to EPZICOM, talk with your healthcare provider before taking it again. Taking EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If your healthcare provider tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a healthcare provider if you need one.

A buildup of lactic acid in the blood and an enlarged liver, including fatal cases, have been reported.

Do not take EPZICOM if your liver does not function normally.

Some patients infected with both hepatitis B virus (HBV) and HIV have worsening of hepatitis after stopping lamivudine (a component of EPZICOM). Discuss any change in treatment with your healthcare provider. If you have both HBV and HIV and stop treatment with EPZICOM, you should be closely monitored by your healthcare provider for at least several months.

Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking EPZICOM as well as interferon with or without ribavirin and you experience side effects, be sure to tell your healthcare provider.

When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your healthcare provider.

Changes in body fat may occur in some patients taking antiretroviral therapy. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms, and face may also occur. The cause and long-term health effects of these conditions are not known at this time.

Some HIV medicines, including those containing abacavir (ZIAGEN, EPZICOM, and TRIZIVIR), may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes, tell your healthcare provider.

The most common side effects seen with the drugs in EPZICOM dosed once daily were allergic reaction, trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of the side effects do not cause people to stop taking EPZICOM. By prescription only.

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 additional important information about EPZICOM, including boxed warnings, on the adjacent pages.

Save on your medication!

Ask your doctor about the Patient Savings Card or visit www.mysupportcard.com to learn how to save on your out-of-pocket expenses. Subject to eligibility. Restrictions apply.

“

EVEN WITH HIV,

I AM UNDEFEATED.” “ When I was diagnosed with HIV, I was worried that the disease would take over my life. But over time, I realized I could fight back. By working on my body, my mind, and my spirit, I became stronger than I ever imagined.

My meds are a big help. Last year, I started taking EPZICOM as part of my combination therapy. My doctor told me that, when used with other medications, it’s been shown to help keep HIV from making more copies of itself and infecting healthy cells. 68% of patients taking a regimen with EPZICOM had their viral load become undetectable in less than one year. In addition, patients saw a 93% increase in their T-cell counts.* Looks like EPZICOM is working well. My viral load is undetectable. And me? I just keep fighting on.” †

†

Not an actual patient testimonial. Based on collection of real patient experiences. Individual results may vary.

* HEAT study of 688 patients defines undetectable as a viral load less than 50 copies/mL. Baseline median T-cell count for patients receiving EPZICOM was 214 cells/mm3 and at 48 weeks, patients saw a median increase of 201 cells/mm3 in their T-cell count.

Ask your healthcare provider if EPZICOM is right for you.

Learn more at www.EpzicomForYou.com

NB: 7 X 9 PBW Line Screen: 133 T:7” EPZICOM® (abacavir sulfate and lamivudine) Tablets MEDICATION GUIDE EPZICOM® (epʹ zih com) Tablets Generic name: abacavir (uH-BACK-ah-veer) sulfate and lamivudine (la-MIV-yoo-deen) Read the Medication Guide that comes with EPZICOM before you start taking it and each time you get a refill because there may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. Be sure to carry your EPZICOM Warning Card with you at all times.

What is the most important information I should know about EPZICOM? • Serious Allergic Reaction to Abacavir. EPZICOM contains abacavir (also contained in ZIAGEN® and TRIZIVIR®). Patients taking EPZICOM may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not. Your doctor can determine with a blood test if you have this gene variation. If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your doctor right away to determine if you should stop taking this medicine.

Symptom(s) Group 1 Group 2 Group 3 Group 4 Group 5

Fever Rash Nausea, vomiting, diarrhea, abdominal (stomach area) pain Generally ill feeling, extreme tiredness, or achiness Shortness of breath, cough, sore throat

What is EPZICOM? EPZICOM is a prescription medicine used to treat HIV infection. EPZICOM includes 2 medicines: abacavir (ZIAGEN) and lamivudine or 3TC (EPIVIR®). See the end of this Medication Guide for a complete list of ingredients in EPZICOM. Both of these medicines are called nucleoside analogue reverse transcriptase inhibitors (NRTIs). When used together, they help lower the amount of HIV in your blood. This helps to keep your immune system as healthy as possible so that it can help fight infection.

Different combinations of medicines are used to treat HIV infection. You and your doctor should discuss which combination of medicines is best for you.

• EPZICOM does not cure HIV infection or AIDS. We do not know if EPZICOM will help you live longer or have fewer of the medical problems that people get with HIV or AIDS. It is very important that you see your doctor regularly while you are taking EPZICOM. • EPZICOM does not lower the risk of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.

Who should not take EPZICOM? Do not take EPZICOM if you: • have ever had a serious allergic reaction (a hypersensitivity reaction) to EPZICOM or any other medicine that has abacavir as one of its ingredients (TRIZIVIR and ZIAGEN). See the end of this Medication Guide for a complete list of ingredients in EPZICOM. • have a liver that does not function properly.

• are less than 18 years of age.

Before starting EPZICOM tell your doctor about all of your medical conditions, including if you: • have been tested and know whether or not you have a particular gene variation called HLA-B*5701.

• are pregnant or planning to become pregnant. We do not know if EPZICOM will harm your unborn child.

You and your doctor will need to decide if EPZICOM is right for you. If you use EPZICOM while you are pregnant, talk to your doctor about how you can be on the Antiviral Pregnancy Registry for EPZICOM. • are breastfeeding. Some of the ingredients in EPZICOM can be passed to your baby in your breast milk. It is not known if they could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

• have liver problems including hepatitis B virus infection.

• have kidney problems.

• have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take any of the following medicines*: • methadone • HIVID® (zalcitabine, ddC) • EPIVIR or EPIVIR-HBV® (lamivudine, 3TC), ZIAGEN (abacavir sulfate), COMBIVIR® (lamivudine and zidovudine), or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine).

431992euro_M01U_PI 0000034660_M01U

What should I avoid while taking EPZICOM? • Do not take EPIVIR (lamivudine, 3TC), COMBIVIR (lamivudine and zidovudine), ZIAGEN (abacavir sulfate), or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine) while taking EPZICOM. Some of these medicines are already in EPZICOM. • Do not take zalcitabine (HIVID, ddC) while taking EPZICOM. Avoid doing things that can spread HIV infection, as EPZICOM does not stop you from passing the HIV 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 or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood.

• Do not breastfeed. EPZICOM can be passed to babies in breast milk and could harm the baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

What are the possible side effects of EPZICOM? EPZICOM can cause the following serious side effects: • Serious allergic reaction that can cause death. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Lactic acidosis with liver enlargement (hepatomegaly) that can cause death. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Worsening of HBV infection. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Changes in immune system. When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.

• Changes in body fat. These changes have happened in patients taking antiretroviral medicines like EPZICOM. 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 cause and long-term health effects of these conditions are not known.

Some HIV medicines including EPZICOM may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.

The most common side effects with EPZICOM are trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of these side effects did not cause people to stop taking EPZICOM. This list of side effects is not complete. 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 EPZICOM? • Store EPZICOM at room temperature between 59º to 86ºF (15º to 30ºC).

• Keep EPZICOM and all medicines out of the reach of children.

General information for safe and effective use of EPZICOM Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use EPZICOM for a condition for which it was not prescribed. Do not give EPZICOM to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about EPZICOM. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for the information that is written for healthcare professionals or call 1-888-825-5249.

What are the ingredients in EPZICOM? Active ingredients: abacavir sulfate and lamivudine Inactive ingredients: Each film-coated EPZICOM Tablet contains the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (OPADRY® orange YS-1-13065-A) that is made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.

COMBIVIR, EPIVIR, EPZICOM, TRIZIVIR, and ZIAGEN are registered trademarks of GlaxoSmithKline. *The brands listed are trademarks of their respective owners and are not trademarks of GlaxoSmithKline. The makers of these brands are not affiliated with and do not endorse GlaxoSmithKline or its products.

This Medication Guide has been approved by the US Food and Drug Administration.

Lamivudine is manufactured under agreement from Shire Pharmaceuticals Group plc, Basingstoke, UK ©2009, GlaxoSmithKline. All rights reserved.

March 2009 EPZ:2MG ©2010 ViiV Healthcare Group of Companies All rights reserved.

Printed in USA.

ECM520R0

June 2010

T:9”

A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you.

If you stop EPZICOM because of an allergic reaction, NEVER take EPZICOM (abacavir sulfate and lamivudine) or any other abacavir-containing medicine (ZIAGEN and TRIZIVIR) again. If you take EPZICOM or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

If you stop EPZICOM for any other reason, even for a few days, and you are not allergic to EPZICOM, talk with your doctor before taking it again. Taking EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If your doctor tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a doctor if you need one.

• Lactic Acidosis. Some human immunodeficiency virus (HIV) medicines, including EPZICOM, can cause a rare but serious condition called lactic acidosis with liver enlargement (hepatomegaly).

Nausea and tiredness that don’t get better may be symptoms of lactic acidosis. In some cases this condition can cause death. Women, overweight people, and people who have taken HIV medicines like EPZICOM for a long time have a higher chance of getting lactic acidosis and liver enlargement. Lactic acidosis is a medical emergency and must be treated in the hospital.

• Worsening of hepatitis B virus (HBV) infection. Patients with HBV infection, who take EPZICOM and then stop it, may get “flare-ups” of their hepatitis. “Flare-up” is when the disease suddenly returns in a worse way than before. If you have HBV infection, your doctor should closely monitor your liver function for several months after stopping EPZICOM. You may need to take anti-HBV medicines.

• Use with interferon- and ribavirin-based regimens. Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking EPZICOM as well as interferon with or without ribavirin and you experience side effects, be sure to tell your doctor.

EPZICOM can have other serious side effects. Be sure to read the section below entitled “What are the possible side effects of EPZICOM?”

How should I take EPZICOM? • Take EPZICOM by mouth exactly as your doctor prescribes it. The usual dose is 1 tablet once a day. Do not skip doses.

• You can take EPZICOM with or without food.

• If you miss a dose of EPZICOM, take the missed dose right away. Then, take the next dose at the usual time.

• Do not let your EPZICOM run out.

• Starting EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If you run out of EPZICOM even for a few days, you must ask your doctor if you can start EPZICOM again. If your doctor tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a doctor if you need one.

• If you stop your anti-HIV drugs, even for a short time, the amount of virus in your blood may increase and the virus may become harder to treat.

• If you take too much EPZICOM, call your doctor or poison control center right away.

People with hepatitis C infection finally have something to look forward to. The new treatments coming down the pike aren’t everything we wish for, but significant progress has been made over the past several years. There are currently more than three dozen new drugs in development that directly target the hepatitis C virus (HCV), some of them in the early research stage and others in large clinical trials.1 Sometime later in 2011 (excluding any unfortunate surprises), hepatitis C treatment will be available that’s somewhat different and more effective than the course of treatment that’s been the standard of care since 1998.1 Two HCV protease inhibitors—Merck’s boceprevir1 and Vertex’s telaprevir2—the first in their class, are furthest in development and are worth following as they move their way toward approval.

In the Beginning…

WORTH THE

WAIT New, more effective therapies for hepatitis C are on the way

When the hepatitis C virus was identified in 1988, the damage that it can cause wasn’t fully appreciated. And HIV had only been identified five years earlier, so immunologists and hepatologists (liver doctors) had their hands full. Many people living with HIV in the early years of the epidemic may have had HCV as well, since both viruses can be transmitted through blood-to-blood contact. But an HCV antibody test wasn’t available until 1990. And at the time, the priority certainly wasn’t determining whether someone had hepatitis C. The priority was to keep people with HIV alive. It wasn’t until the late ’90s, when there were many antiretrovirals available to make up the first combinations of drugs used to treat HIV, that people began paying attention to HIV/hepatitis C co-infection. It was then that we discovered that as many as 25% of people living with HIV are co-infected with hepatitis C.3

Hepatitis C and the Liver

By James Learned

P o s i t i v e lyAwa r e . c o m

HCV replicates in liver cells. Over time, usually a period of years, this viral J a n u a r y + F e b r u a r y 2 0 1 1 | 15

Only about 25% with HCV mono-infection will progress to severe liver disease and need treatment. Many will never progress and don’t need treatment.

It isn’t possible to predict who will fall into that 25%. replication can cause serious liver scarring, or cirrhosis. People with cirrhosis are at risk for liver cancer, liver failure, and other serious health problems.4 People who are co-infected usually have higher amounts of hepatitis C virus in their blood than people with only HCV. 5 Having a higher HCV viral load means that there’s more virus present, which can cause cirrhosis and other liver damage to occur more quickly.

Most people who are co-infected with HIV and HCV suffer more serious liver disease than their HIV-mono-infected counterparts do.6 Liver damage can harm the entire body since the liver has hundreds of functions, including filtering our blood.

When it comes to HIV treatment, liver damage can make it more difficult for the liver to properly break down antiretrovirals and other medications that we’re taking.

If the liver has trouble breaking down antiretrovirals, levels of the drugs can build up, causing more severe side effects and possibly less effective treatment for HIV.

Current Treatment Current HCV treatment consists of a combination of pegylated interferon (Pegasys or PegIntron), which is injected subcutaneously (under the skin) once a week, and ribavirin, which is taken orally two times a day. For people who have hepatitis C only (mono-infected), treatment lasts six or twelve months depending on the specific genotype of HCV the person has.7 After 48 weeks of treatment with pegylated interferon and ribavirin, 45-55% of people with mono-infection achieve a sustained viral response (SVR)—an undetectable HCV viral load maintained six months after finishing treatment. 8 A sustained viral response is generally considered a cure. This is one of the primary differences between HIV treatment and HCV treatment. In HIV, successful antiretroviral treatment results in an undetectable HIV viral load. If the HIV medications are stopped, however, the viral load usually returns to pre-treatment levels. In hepatitis 16 | J a n u a r y + F e b r u a r y

2011

C, an undetectable viral load six months after finishing HCV treatment—an SVR— almost always remains undetectable.

That’s why an SVR is considered a cure.

There are at least six different genotypes of the hepatitis C virus—genotypes 1, 2, 3, 4, 5, and 6.9 Each genotype is a slightly different strain of the virus. They can all cause similar liver damage and HCV disease progression, but some genotypes respond better to current HCV treatment than others do.

HCV genotype 1 is the most difficult genotype to treat.10 After a year of treatment, fewer than 50% of mono-infected people with genotype 1 achieve a sustained viral response.11 Unfortunately, genotype 1 is also the most common strain of hepatitis C in the United States.

Approximately 75% of people with HCV in the U.S. have genotype 1.12, 13 People with mono-infection who have genotypes 2 or 3 require only six months of treatment, and the response rate is 70-80%.

Treatment success rates are considerably lower in people with both HCV and HIV, whichever genotype they have. For people with co-infection, deciding whether to begin often-debilitating HCV treatment is extremely difficult.

The length of treatment for people with co-infection is one year, whatever the person’s genotype, because it’s more difficult to treat HCV in people who are also HIV-positive. And some medical providers recommend 18 months of treatment for people with HIV and genotype 1.14 Two additional measurements provide useful information as to whether or not an individual on treatment is likely to achieve an SVR: the early viral response (EVR)— having an undetectable HCV viral load or at least a two log decrease in viral load at week four—and the rapid viral response (RVR)—having an undetectable HCV viral load after three months of treatment.

Patients with an early viral response have high rates of sustained viral response, but should be encouraged to remain on therapy

for the standard duration of therapy for HCV genotype 1. People who have a rapid viral response also have high rates of sustained viral response and may be able to stop treatment successfully after 24 weeks.

The Big Question: When to Treat?

Not everyone with hepatitis C needs treatment. Only about 25% of people with HCV mono-infection will progress to severe liver disease and need treatment. Many will never progress and don’t need treatment. It isn’t possible to predict who will fall into that 25%. Usually, a doctor monitors fibrosis and starts treatment if signs of progression appear.

Although no one enjoys having a liver biopsy, they’re often recommended in order to tell what’s really going on.

Deciding whether to treat HCV in people with HIV depends on various factors: whether HIV disease is under control; whether there’s an immediate risk of liver disease progression (the presence of fibrosis, for example); and the likelihood of achieving a sustained viral response (the HCV genotype, HCV viral load, the degree of liver damage, and adherence issues).

The complications that co-infection can cause and the lower likelihood of achieving a sustained viral response have led many people to postpone treating their hepatitis C. Just about anyone who’s gone through HCV treatment, or heard about it from friends and colleagues, knows that it isn’t the easiest treatment to endure, to put it mildly. As with any treatment, there are some people who experience very few side effects—or even none at all. Although people who don’t experience side effects may be few in number, they do exist. It happens. And more power to them!

Many people who have gone through HCV treatment relate horror stories after experiencing many of these side effects.

Some patients successfully use antidepressants and blood cell growth factors to manage some of them. But other people P o s i t i v e lyAwa r e . c o m

Many people who have gone through HCV treatment relate horror stories after experiencing side effects... But others with HCV have decided to wait until new drugs are available that cause fewer side effects. with HCV for whom treatment would be appropriate have decided to wait until new drugs are available that cause fewer side effects and are more effective than the current treatment.

New Protease inhibitors Telaprevir and boceprevir are both hepatitis C protease inhibitors. HIV protease inhibitors are familiar since they were first approved as components of HIV treatment in the late 1990’s. Hepatitis C is a considerably less sophisticated virus than HIV is and infects liver cells very differently than the way that HIV infects immune system cells. But HIV’s protease enzyme and HCV’s protease enzyme have similar functions in cell replication. Any drug that slows down—or inhibits—the function of the protease enzyme interferes with viral replication, which is a really good thing!

First, the not so good news: Both of these new drugs need to be taken with pegylated interferon and ribavirin (although hopefully for a shorter period of time).18, 19 This isn’t surprising, but it’s still disappointing. Almost everyone who has taken or considered taking interferon looks forward to the day when it will no longer be a component of HCV treatment. Although the demise of interferon as part of HCV treatment isn’t in the immediate future, some innovative research looking at the possibility of treating HCV without interferon is in its early stages.

The good news: Recent data from clinical studies of telaprevir and boceprevir are very promising. These new drugs show an improvement in efficacy. Using either one will probably require being on treatment for less time and is much more likely to result in a sustained viral response. 20

Clinical Trial Results The telaprevir and boceprevir clinical trials are complicated in design, requiring that participants take the study drug or a placebo plus interferon/ribavirin for 12 or more weeks followed by interferon/ribavirin without the study drug for up to a year. The P o s i t i v e lyAwa r e . c o m

following examples illustrate the success that both drugs have shown to date.

Telaprevir The results of a Phase 2b trial of telaprevir were published in the New England Journal of Medicine in April 2009. 21 The study showed that adding telaprevir to standard HCV therapy (pegylated interferon and ribavirin) significantly increased response rates and shortened the length of treatment for people with genotype 1, all of whom were mono-infected.

Sixty-one percent of the study participants who took telaprevir, pegylated interferon, and ribavirin for three months followed by pegylated interferon and ribavirin (but no telaprevir) for another three months achieved a sustained viral response. In other words, adding telaprevir to standard treatment shortened the length of therapy needed to achieve a sustained viral response (SVR) to only six months and significantly increased the percentage of people who achieved an SVR. These results are particularly impressive because everyone in the trial had the difficult-to-treat genotype 1.

At the end of April 2010, Vertex Pharmaceuticals issued a press release describing the results of another telaprevir study. 22 Three-quarters (75%) of genotype 1 HCV mono-infected participants who took telaprevir, pegylated interferon, and ribavirin for three months, followed by either 12 or 36 weeks of pegylated interferon and ribavirin (but no telaprevir) attained a sustained viral response.

interesting result was that 66% of the participants who were on all three drugs achieved a sustained viral response.

The study included a comparatively high percentage of participants who identified themselves as African American or black, a population that doesn’t respond well to interferon-based therapy. This discrepancy isn’t well understood, but seems to be related to genetic factors rather than to socioeconomic issues or a lack of access to care. The researchers described each finding by race. Although 66% of all participants who were on the three drugs achieved an SVR, for example, only 53% of African Americans/blacks in that arm achieved an SVR, while 69% of participants of other races in the arm achieved that result. As studies include more African American participants and report the results by race, we may learn more about the reasons why HCV treatment isn’t as effective in that population.

Telaprevir and Boceprevir The results of treatment with either telaprevir or boceprevir are impressive and promising. Since only about 50% of monoinfected patients with genotype 1 achieve a sustained viral response after one year of treatment with pegylated interferon and ribavirin, the potential of having access to treatment that will increase that percentage to 60% or more—and may require less time on treatment—is exciting.

Both telaprevir and boceprevir have also been shown to be effective for people who didn’t attain a sustained viral response when they went through treatment previously.24, 25

Boceprevir In November, results were presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases23 of a study of boceprevir in combination with pegylated interferon and ribavirin.

The 1,097 study participants were all mono-infected with genotype 1 and had never gone through HCV treatment before.

The study design was complex. The most

Side Effects Side effects in people taking telaprevir or boceprevir included rash, itching, nausea, and anemia. 26, 27 One participant taking telaprevir experienced Stevens-Johnson syndrome, a rare but life-threatening rash. 28 Mild to moderate rashes were quite common. During the remaining telaprevir trials and then in clinical practice, any rash J a n u a r y + F e b r u a r y 2 0 1 1 | 17

We can thank the work that’s been done in HIV for helping to develop better treatments and treatment strategies for other viruses, including hepatitis C. will need to be monitored very carefully to figure out whether the single case of Stevens-Johnson syndrome in the trial was an anomaly or a rare side effect.

Co-infection Clinical trials of telaprevir and boceprevir are underway to determine whether the drugs are safe and effective in people co-infected with HIV and HCV. As in the studies discussed above, all participants must have genotype 1. 29, 30 With current HCV therapy, sustained virologic response only occurs in 35-46%31 of people with co-infection, depending on other factors.

It will be at least two years before we know whether adding either telaprevir or boceprevir to standard HCV treatment is as successful in co-infection as they have so far proven to be in mono-infection.

Using these new drugs in co-infection, even once they’re approved for that purpose, will involve some trial and error. For example, drug interactions with telaprevir, boceprevir, and HIV antiretrovirals are possible, which could be a big deal considering the number of drugs that some people with HIV take. And the duration of treatment with these new HCV drugs may be different for people who are co-infected—something we won’t know until the co-infection trials are completed and analyzed.

Yet there’s great promise here. These are the first drugs that directly interfere with HCV replication, so co-infection may not interfere with successful HCV treatment as it has with interferon and ribavirin therapy.

Lessons Learned Scientists and community members have

Our annual Poz Cruise is open to people of all sexualities.

Take part in planned activities for gay travelers and straight shipmates alike. Our private shipboard events and exclusive shore excursions offer uplifting social and educational activities. Make new friends or maybe even meet your new partner. By the end of the week, you’ll have many fond memories.

In 2011, we’ll sail from Ft. Lauderdale to Aruba, Curacao, and Princess Cay aboard the beautiful Crown Princess.

Gay group: www.hivcruise.com Straight group: www.positivecruise.com e-mail: paul@cruisedesignstravel.com or call: (954) 566-3377.

a better understanding of other viruses thanks to our continually increasing knowledge of HIV. Research doesn’t happen in a vacuum, and we can thank the work that’s been done in HIV for helping to develop better treatments and treatment strategies for other viruses, including hepatitis C. If nothing else, the hope of new discoveries keeps us motivated and determined to see what tomorrow brings. e James Learned is an advocate, writer, and trainer, focusing on HIV and viral hepatitis treatment, psycho-social issues, active listening skills, and helping social service providers work most effectively with clients.

Go to PostivelyAware.com for references.

POZ Cruise

November 5-12, 2011 Starting at $659, plus $67 tax.

WIN A trip for 2 aboard the poz cruise!

For details, rules, and to learn how to enter, go to

www.positivelyaware.com

Rates are per person based on double occupancy. Capacity controlled. Ship’s registry: Bermuda.

18 | J a n u a r y + F e b r u a r y

2011

P o s i t i v e lyAwa r e . c o m

Ask the HIV Specialist Wayne T. Dodge, MD, AAHIVS

Positive about flu shot Q: I have been HIV-positive for about nine years now. My T-cells are under 200, but my doctor tells me I am “very stable” on my HIV meds. Despite this, he strongly suggested the flu vaccine again this past fall, and I allowed him to give me the shot.

I really didn’t want to take it because it makes me nervous and seems to actually make me feel sick. I read somewhere that if you feel sick this means you may be getting the best benefit from it. Is this true? Is the flu shot a good idea for people like me who have had HIV for a long time?

—Jerel Seattle, WA A: This is a great question, Jerel, and as with so many questions about treating those with HIV, it does not have a perfectly simple answer.

First, there are two types of flu vaccines available. One is a “live-attenuated” vaccine (this means that the virus has been altered so that it can’t cause significant illness), which is given nasally. The other is an inactivated vaccine which is given as a shot. Only the shot is recommended for those who are HIV-positive, as there is concern that with a challenged immune system, even an attenuated virus could cause some problems.

Second, it is not possible to “get the flu” from the shot itself. There is no live virus in the shot. Thus, all of the “feeling bad” after getting the shot is a reaction to the shot itself. The process to make the vaccine involves growing the virus on eggs, so if you have an egg allergy, this may cause some of the side effects that you’ve experienced. If this is the case, you should consult your doc about the risk/benefit of getting the vaccine with the history of egg allergy in mind. Otherwise, the reaction P o s i t i v e lyAwa r e . c o m

(other than the localized arm soreness just from the shot itself) is likely to be your body’s reaction to the viral proteins in the shot, which is what protects you from becoming infected by the actual virus. That protective response by the body is really the whole point of the vaccine, but there is no clear evidence that if you get physical side effects after a flu shot that you have any better (or worse) protection from the flu than if you have no reaction.

Finally, we do have studies on the use of flu shots in those with HIV that clearly show benefit. In one study of flu vaccine in HIV-positive individuals, only 6% of those getting the vaccine got the flu, while 21% of those who did not get the vaccine got the flu during the same season. In another study, those who got the flu shot had a significant reduction in symptoms (respiratory illness), as well as actual evidence of getting infected with influenza itself. What we don’t know is whether or not your low CD4 count (and I’m very glad that you’re stable—keep taking those antiretrovirals) makes it less likely that you’d be protected from getting the flu than another HIV-positive person with a higher CD4 count. We do know from the first study quoted above that those with CD4 counts less than 200 had a less robust antibody response to the vaccine than those with higher CD4 counts, but the study was unable to look at whether this difference in antibody response translates into a difference in getting ill or not.

So, in summary, here’s what I’d

recommend for you and others in your shoes (and this is always with the caveat of consulting with your own personal physician, of course): Unless you know that you have a significant egg allergy—or that your previous reaction to the immunization was severe (i.e., you needed to stay in bed because of the reaction)—you should get the flu shot. Your decision to take the shot this year was a good one. Hope this is helpful!

—Wayne T. Dodge, MD, MPH, AAHIVS HIV/AIDS Program Chief Group Health Cooperative Seattle, WA

Submit your questions to AAHIVM@tpan.com Due to space limitations, not all submitted questions can be answered in this column. For more information about AAHIVM, call 202-659-0699 or visit www.aahivm.org.

Search for an HIV Specialist™ Finding an HIV Specialist™ is easy with AAHIVM’s Find-A-Provider directory at www.aahivm.org.

Click on the “Find-A-Provider” window on the home page, enter your location, and click on the search button for a list of HIV Specialists™ near you.

J a n u a r y + F e b r u a r y 2 0 1 1 | 19

Conference REPORT reported by Jeff Taylor

November is a busy month for conferences in Europe with both the International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV in London, and the Tenth International Congress on Drug Therapy in HIV Infection in Glasgow. It was 10 days of cold, rainy weather —and lots of science. Here are some highlights.

InflaMmatory remarks An ongoing theme at both meetings was inflammation believed to be caused by HIV infection itself (even when the virus is made undetectable by the meds).

This inflammation is linked to many of the lipodystrophy and aging complications we’re seeing in people living long term with HIV, such as cardiovascular disease, kidney problems, and neurocognitive issues. Other studies presented showed a relationship between bacteria markers in the blood and blood vessel damage—a risk factor for cardiovascular disease. And the level of HIV virus in the blood seems to be important in terms of inflammation as well—one French study 20 | J a n u a r y + F e b r u a r y

showed that patients with a viral load of less than 40 copies had much lower levels of the inflammation markers IL-6 and C-reactive protein.

This suggests that it might be better to be on a therapy that keeps the viral load extremely low to prevent the problems possibly caused by inflammation.

One especially intriguing theory is that HIV infection damages the lining of the gut—causing “leaky gut syndrome” that allows the naturally present bacteria to get into the bloodstream. These bacteria in the blood make the body mount an inflammatory immune response—which could be a cause of the chronic inflammation we see in people with HIV. Remy Burcelin of France gave a 2011

fascinating plenary talk linking these intestinal microflora and metabolic disease. They gave two groups of normal weight, germ-free mice (think Bubble Boy) the gut microbes from either lean mice or from fat mice. The mice that got the microbes from the fat mice got much fatter than the ones who got the lean mice microbes—suggesting that the gut microbes themselves can cause weight gain. They showed that normal mice fed a high fat diet release more bacteria with a molecule on their membranes that cause the immune system to react, measured by inflammation markers in the blood. In people who are insulin resistant (pre-diabetic) vs. people with normal blood sugar, similar differences in gut flora are found as in the fat and skinny mice. Further tests showed that fat mice have much higher than normal levels of bacteria in their fat tissue.

So does this mean a daily dose of yogurt or a magic probiotic pill will prevent all our problems? Too soon to say, but look for studies of antibiotics that target the bacteria in the gut to see if lowering their levels will lower inflammation and possibly have an effect on things like the blood vessels, which could help prevent cardiovascular disease and other inflammationrelated problems.

Shape of things to come The London workshop— still known by its former moniker of the Lipodystrophy workshop—has traditionally focused on the metabolic

problems like body shape changes, bone density loss, diabetes, and other problems with insulin and blood sugar. Continuing its focus on lipodystrophy was a study confirming that switching from the older nukes like d4T and AZT to Truvada or Epzicom can stop fat loss, and cause mild improvement over the two years studied. The fat gains are modest—with more than half of the patients switching to either drug having a 10% increase in limb fat over 96 weeks. This is not enough to correct the problem in patients with severe lipoatrophy—especially the facial wasting that is so stigmatizing for many.

Disturbingly, there was a presentation on the complications of one widely used facial filler—Bio-Alcamid. Several years after the filler is injected, many patients are experiencing infections in their faces, requiring surgery to remove the filler. Often it is caused by dental work or other trauma, but it can happen spontaneously as well. Bio-Alcamid was never approved in the U.S., but many people traveled to Canada or Mexico to have their facial wasting corrected.

It is no longer used in either place, and patients who have Bio-Alcamid are recommended to get prophylactic antibiotics when having any dental work done, and contact their doctor immediately if they notice any redness or swelling around the injection site.

PMMA (polymethylmethacrylate), a filler popular in Brazil for facial wasting that has not been associated with many complications, was the subject P o s i t i v e lyAwa r e . c o m

of a poster describing its use for reconstructing wasted buttocks (aka AZT butt). This can be a painful problem for many HIVers, and the surgical plastic or silicone prostheses some have resorted to have also been plagued with problems. The poster showed some dramatic photos of the wellrounded results, and despite the large amounts of PMMA injected, there were no major problems reported.

One bit of good news during the workshop was the FDA’s approval of the only therapy to help reverse fat gain in the belly (aka lipo belly). Long-awaited Egrifta—the new brand name for tesamorelin—is growth hormone releasing factor that stimulates the body to produce its own natural growth hormone (see The Buzz, page 34). Like its cousin Serostim, a growth hormone long used to combat AIDS wasting, Egrifta will require a daily injection in the skin of the belly. But it does produce a moderate reduction of belly fat by up to 18%. A study of whether it could also improve

P o s i t i v e lyAwa r e . c o m

markers of cardiovascular risk had mixed results—with some markers showing moderate improvement, but not in the one most commonly associated with heart disease (CRP, or C-reactive protein). So more long-term studies will be needed to show whether the fat loss from Egrifta will translate into a lower risk of heart disease. But in the meantime, patients finally have a tool besides diet and exercise to help them battle their lipo bellies. Previous studies have shown that none of these by themselves can completely reverse the fat gain, and hopefully a study will be done to see whether the commonsense approach of combining all three—diet, exercise, and Egrifta—will give HIVers the relief they need.

‘D’ is for DeficIency A common theme at both conferences was vitamin D—a hot topic in HIV these days. Recent research has shown that most people in the general population are vitamin D deficient—which

has been linked to everything from bone loss to cardiovascular disease to prostate cancer. Numerous studies presented showed vitamin D levels in people with HIV to be lower in winter, in people with darker skin, in older people, and in those taking efavirenz (Sustiva) and tenofovir (Viread, Truvada). Both meetings convened plenary sessions on the topic, and while there were numerous studies presented showing an association between vitamin D deficiency and many complications, it was hard to show whether the deficiency caused the problems or was just a symptom—a classic chicken or egg dilemma. One area where the experts did agree was the importance of vitamin D in preventing bone loss (osteopenia and osteoporosis). There is ample evidence in the general population that supplementing vitamin D can both stop and reverse bone loss, and the experts believed the same would be true for HIV. So what’s the take home message for HIVers? During the Q&A sessions the experts all agreed that anyone with HIV should be tested for vitamin D deficiency—it is now part of the European guidelines for HIV care. There was much discussion of how much vitamin D to give. When someone is diagnosed as deficient, it often requires megadoses to get them up to normal. Thereafter, it was agreed that a daily supplement of 200 to 600 IU a day should be enough. (The daily amount goes up as you age— older people need more).

(Not-so) Old news Another unifying topic at both meetings was the issue of aging in HIV. Many of the problems HIVers are facing these days look like aging, but is it really just accelerated aging, a result of HIV infection and/or the meds, or a combination of both? A fascinating talk in Glasgow by Brendan Payne of the UK focused on how mutations in the mitochondrial DNA—the socalled “powerhouse” of every cell—could be responsible at a cellular level for the agingrelated problems experienced by HIVers. He showed that cumulative exposure to HIV nukes (d4T, AZT, etc.) caused irreversible damage to the mitochondria that mirrors the damage seen in ordinary aging. This seems to support another talk at the lipo workshop showing that the length of time on HIV drugs and the lowest CD4 count predicted the onset of agingrelated complications. We may now have an insight as to the problem’s cause, which could be the first step to finding treatments to help HIVers live longer, healthier lives.

For webcasts and abstracts, go to www. intmedpress.com/lipodystrophy and www.hiv10.com.

Jeff Taylor is an AIDS activist living in Palm Springs, California. He’s a member of the AIDS Treatment Activists Coalition, the AIDS Malignancy Consortium, on the DHHS Guidelines Panel, and conducts a monthly HIV treatment education program in Palm Springs.

J a n u a r y + F e b r u a r y 2 0 1 1 | 21

Point of

origin The discovery and spread of HIV

By Alicia M. Prater, PhD

Human retroviruses were thought to be nonexistent prior to the discoveries of two human T-cell leukemia viruses (HTLVs) in the late 1970s. When the mysterious syndrome of chronic immunodeficiency spreading among gay men (and later intravenous drug users and hemophiliacs) was first recognized in 1981, researchers found a link with the new retroviruses—CD4 T-cell depletion.

As explained by Drs. Robert Gallo and Luc Montagnier in their December 2003 retrospective in the New England Journal of Medicine, the human retroviruses were clear candidates as the cause of the

22 | J a n u a r y + F e b r u a r y

2011

disease, but between 1982 and 1984 HTLV was ruled out as the causative agent.

Instead, the researchers discovered yet another human retrovirus—HIV. With the new field of human retrovirus

study in the early 1980s, researchers were poised to deal with AIDS and to discover HIV, but how long did it go unrecognized in the human population, and where did the virus come from?

Lentiviruses, the family to which HIV belongs, have a long history of infecting several animal species, including cats (feline immunodeficiency virus, or FIV), horses (equine infectious anemia virus, or EIAV), and monkeys (simian immunodeficiency virus, or SIV). Several primate species in Africa, including chimpanzees and African green monkeys, have asymptomatic infections with SIV, similar to

P o s i t i v e lyAwa r e . c o m

Despite the speculation of when and where the first AIDS case appeared, the virus had clearly become pandemic by the time the disease was recognized.

The first report of AIDS in the U.S. was published by the CDC in June 1981. long-term non-progressor HIV-positive humans (elite controllers). In contrast, when some species that are not naturally infected, such as macaques, are exposed to the virus, they develop simian AIDS. Silvestri et al. reviewed the mechanisms underlying this difference in The Journal of Clinical Investigation in 2007. The differences appear to stem from variations in the CD4 co-receptors on T-cells, a mechanism now understood to contribute to differentiating the infectivity and course of HIV in humans.

Because of this natural prevalence of the virus among monkeys, bushmeat in central Africa has a high rate of SIV infection, putting hunters and butchers in that region of the world at risk for zoonotic infections (diseases that normally exist in animals but can infect humans). Reporting in The Lancet in 2004, Wolfe et al. showed that simian viruses are capable of being readily transmitted to humans. Exposure to contaminated blood and meat is generally accepted as being the route by which HIV made its way into the human population.

HIV strains are genetically different from classical SIV strains due to the presence of an extra regulatory gene, which slightly differs among the two human strains due to crossover. Phylogenetic analyses of naturally occurring lentiviruses have identified recombinant lineages of HIV and SIV in central Africa. The years of genetic studies have shown that primates are the ancestral source of and reservoir for both HIV-1, the most prevalent strain worldwide, and HIV-2, a less common strain mostly isolated to western Africa.

The HIV-1 species jump is thought to have occurred at least four times, allowing for the establishment of endemic human infections of different HIV-1 groups, similar to what is seen with influenza viruses that cross among birds, swine, and humans.

The virus begins to diversify once it has a human host, increasing genetic variability as it spreads. Multiple subgroups P o s i t i v e lyAwa r e . c o m

of the virus have developed, some more infectious and virulent than others, with HIV-1 group M (major group, as opposed to O, or outlier, and N, or non-M/non-O) gaining strength as a pandemic strain. As the birthplace of HIV, Africa still bears the brunt of AIDS globally—with more than three-fifths of all HIV infections occurring in the World Health Organization’s (WHO) African Region (as of the 2007 WHO Epidemiological Surveillance Report).

The ancestral sources of SIVcpz/ HIV-1 and SIVmac/HIV-2 are arboreal guenons and sooty mangabey monkeys, respectively, according to a review in Clinical Microbiology Reviews in 2006.

The National Institutes of Health (NIH) HIV sequence database suggests that HIV-1 M is the result of a single transmission event from chimpanzees, with the subtypes resulting from divergence in humans. HIV-1 O is thought to have been transmitted to humans from wild gorillas. A new group, P, was proposed in 2009 to describe a rare strain in Cameroon related to SIVgor.

Similarly, HIV-2 is growing with new nomenclature for its own groups (A, B, C, F, G), each representing a unique transmission event between primates and humans.

The first transmission of the immunodeficiency virus from primate to human occurred prior to 1931, as reported in separate studies in Science in 2000 and 2006.

The appearance of the human virus is dated to approximately that time (margin of error 15 years) based on HIV-1 reservoirs of specific SIV strains in chimpanzees. The virus then spread and mutated among the western and central African populations.

A report in Nature in 1998 indicated the presence of HIV in a blood plasma sample obtained from an African in 1959 that resembled two subtypes of HIV-1 group M. Another report in Nature, in 2008, identified HIV in a tissue sample taken from a woman from the Belgian Congo in 1960, supporting measurable human infection with HIV by that time.

Other reports indicate that some

individuals outside of Africa were infected with HIV-1, and possibly died from AIDS, around that same time, decades earlier than the pandemic spread of HIV to the United States. In 1997, the journal Virology published an analysis of blood from a Norwegian family that died in the mid1970s after an AIDS-like illness. They were found to have been infected with HIV-1 group O prior to 1970.

According to a genetic analysis published in 2007 in the Proceedings of the National Academy of Sciences (PNAS) by the Department of Ecology and Evolutionary Biology at the University of Arizona and researchers at the University of Miami, the first epidemic of HIV outside of Africa started in the Caribbean in the 1960s.

In 1979, the Miami medical community started reporting a mysterious illness in some Haitian immigrants. The researchers used stored blood samples from these patients and blood samples from early AIDS patients to trace the lineage of HIV in this immigrant population. The PNAS study found that HIV likely made its way to Haiti from Africa sometime around 1966, and then to the Unites States in approximately 1969, most likely in a single patient. HIV was circulating in the United States for at least a decade before AIDS was recognized.

Despite the speculation of when and where the first AIDS case appeared, the virus had clearly become pandemic by the time the disease was recognized. The first report in the United States of what was later called AIDS was published by the U.S. Centers for Disease Control and Prevention (CDC) in June 1981. As reviewed by the agency in June 2001, the Morbidity and Mortality Weekly Report from that time reviewed cases of Pneumocystis carinii pneumonia in healthy young men in Los Angeles, citing their cause as “cellularimmune dysfunction related to a common exposure,” which prompted additional reports from other major American cities, including New York and San Francisco.

Eighteen months later, the CDC had a list J a n u a r y + F e b r u a r y 2 0 1 1 | 23

New transmission events, mutation, and recombination among circulating strains are increasing the complexity of treating HIV.

of risk factors for the immune dysfunction, which by that point had been termed AIDS. The discovery of HIV was still not clear when the initial recommendations for preventing infection were issued in 1983.

The discovery of the virus known as HIV has been credited to the United States and France. In 2008, the Nobel committee decided that the French group consisting of Luc Montagnier and Francoise BarreSinoussi were the first to identify the new pathogen and awarded them the 2008 Nobel Prize for Physiology or Medicine.

However, as explained by Richard Knox for NPR (National Public Radio) in 2008, many felt that American researcher Robert Gallo deserved to share in the prize. According to Gallo and Montagnier’s 2003 retrospective, Montagnier’s lab at the Pasteur Institute was the first to obtain a clear-cut isolate of the human retrovirus that causes AIDS. Gallo’s lab at the National Institutes of Health in Bethesda, Maryland, built on this 1983 discovery, finally unraveling the cause and effect in the development of the immune deficiency after infection. Gallo is the one credited with proving that HIV is the etiological agent underlying AIDS. By 1984, the work from these two laboratories finally illuminated the cause behind the tens of thousands of cases of AIDS being diagnosed in the United States at that time.

In 1985, this work led to a blood test for the presence of HIV, which was made available to blood transfusion centers, minimizing its transmission to hemophiliacs and surgical and trauma patients. The 1992 International Conference on AIDS 24 | J a n u a r y + F e b r u a r y

2011

estimated that 5% of hemophiliacs in the United States were HIV-positive due to blood transfusions or clotting products they received between 1978 and 1985.

The first FDA approved treatment for HIV infection and AIDS was Retrovir (AZT, zidovudine) in March 1987. That same year, a more specific blood test for HIV antibodies was approved and the first vaccine candidate tested. Almost 25 years later, a viable vaccine has yet to be found.

Many AIDS patients could not tolerate the antiretroviral therapy, so the FDA stepped up pre-approval procedures for drugs to treat the opportunistic infections, such as trimetrexate for pneumocystis pneumonia in 1988. Another problem with antiretroviral therapy was resistance.

HIV has a high rate of mutation when it replicates. Drug cocktails were necessary to keep up with changes in the virus and prevent escalating infection. The mixture of three or more antiretroviral drugs is now known as HAART (highly active antiretroviral therapy), which was introduced as a standard regimen in 1996. However, the regimen needs constant medical surveillance for resistance, and Stanford University maintains a public HIV Drug Resistance Database to aid in the surveillance and treatment of infection.

In the 40 years that followed the arrival of the virus in the Caribbean, HIV-1 group M subtype B became the predominant strain in that region of the world and North America. HIV-1 M is divided into various clades, or subtypes, currently denoted by the letters A-K. As new strains are

discovered, a new letter is used. Each strain has some genetic variability from the others, representing distinct lineages of HIV-1 M. However, retroviruses are capable of combining with genetically similar subtypes when present in the same host, resulting in recombinant forms. Circulating recombinant forms (CRFs) of HIV have been described since at least 1993, adding to the variability and survivability of the virus in the human population. CRFs have been identified in Asia, Africa, Russia, the Mediterranean, South America, Spain, Saudi Arabia, and Cuba according to the Los Alamos/NIH database of HIV sequences.

The first HIV-2 CRF was identified last year.

New transmission events, mutation, and recombination among circulating strains are increasing the complexity of treating HIV. Over the last nearly three decades, research has traced the ancestry of the many HIV strains, finding more extensive and continuous spread than previously thought. e This is the first in a special three-part series sponsored by Abbott Molecular.

Alicia Prater has a PhD in Experimental Pathology, and has taught graduate level pathology, including infectious diseases and HIV/AIDS. Special thanks to Michael Worobey for reviewing this article.

Go to PostivelyAware.com for references.

P o s i t i v e lyAwa r e . c o m

HIV WELLNESS SERIES Bob Munk

Who knew?

We never thought we’d live this long

When I got my positive HIV test result in 1987, there was no such thing as “HIV and Aging.” In San Francisco, people who tested positive had less than a year to live.1 My doctor told me I should “find my place in the universe” and be sure my will was up to date.

The 1996 International AIDS Conference in Vancouver provided a surge of hope in the grim scheme of AIDS. Combination therapy including the new protease inhibitor drugs seemed to hold the promise of a cure. People with HIV faced a major adjustment. Maybe it wasn’t such a good idea to max out the credit cards (after all, we wouldn’t be around to pay the bills) and work our way down our “bucket list,” whatever the cost. Maybe we would be around long enough to have a serious relationship, to go to graduate school—to have a life!

The life expectancy of people living with HIV increased dramatically after 1996.2 As the death rates from AIDS declined, other diseases emerged for people with AIDS: liver, kidney, and cardiovascular disease; non-AIDS cancers, and diabetes. 3 The list of things to do to stay healthy with HIV got a lot longer. Taking antiretrovirals is as important as ever, but traditional factors such as smoking, diabetes, and exercise take on new importance.4 Our hopes for a cure faded as HIV proved to be able to persist in the face of the best medications we had. In the last decade, our concerns shifted to health issues we also didn’t expect, such as osteoporosis, hypertension, heart disease, P o s i t i v e lyAwa r e . c o m

memory loss, and frailty. These are the diseases associated with old age, which we never expected to reach.

3. Older people may become newly infected with HIV. In New York City, women over 50 years old accounted for 22% of new HIV infections in 2008.7 Several factors contribute to the increase in older people getting infected with HIV: n

Health care providers may not test older people for HIV infection. This may be because they don’t perceive their patients as being sexually active or at risk for HIV infection.

n

Older people may lack awareness of the risk factors for getting HIV. Very little HIV prevention education is targeted at older people. Many older people believe that HIV only affects younger people, and most older people get no training in safer sexual activities.

n

Many older people are newly single.

They get divorced or lose their mates.

While they had a partner, they may have ignored HIV prevention messages; when going back into social settings, they may believe that they are not at risk for HIV infection.

n

Drug use accounts for more than 16% of infections of people over 50. Again, health care providers may not perceive that their patients are engaging in this type of risk behavior.

n

Older patients may be engaging in

THE OLDER POPULATION WITH AIDS IS INCREASING Age 50 is the cutoff used by the U.S. Centers for Disease Control and Prevention (CDC) to keep statistics on “older people” with HIV and AIDS. The most recent CDC statistics for AIDS by age are from 2005.

They show that people age 50 years and older accounted for 19% of all AIDS diagnoses, 29% of persons living with AIDS, and 35% of all deaths of persons with AIDS.5 The number of older people diagnosed with AIDS is increasing. There are several types of seniors being added: 1. People with HIV are aging due to the success of combination antiretroviral medications, which has lengthened the life span of people infected with HIV. This is the major factor contributing to the increase in seniors in New York City.6 2. Some older people are just learning that they have been infected with HIV, perhaps for several years.7 Age is related to late diagnosis of HIV. 8

J a n u a r y + F e b r u a r y 2 0 1 1 | 25

The number of people over 50 with HIV or AIDS is growing rapidly.

Life expectancy after a diagnosis of HIV doubled from 1996 to 2005.

unprotected sexual activity. This may be heterosexual or homosexual sex.

The use of Viagra and other drugs that help men get and maintain an erection contribute to increased rates of sexual activity and sexually transmitted diseases among older people, as they do for younger people. n

Physicians may not accurately diagnose HIV infection in older people. Some early symptoms of HIV disease are easily confused with other diseases of normal aging.

n

The stigma of having HIV/AIDS may be worse for older people. This can result in hiding their infection from family and friends, as well as from their health care providers.

HIV IN OLDER PEOPLE The first studies of HIV in older people were done before strong anti-HIV drugs were available. Most of them showed that older people got sicker and died faster than younger people. This was thought to be due to the weaker immune systems of older people. More recent research shows that older people respond well to antiretroviral treatment. Most older patients, unless they are drug users or have mental problems, take their medications more regularly than younger patients: they have better adherence.9 HIV disease status is typically measured by CD4 cell levels and HIV viral load.

The CD4 counts are supposed to indicate the strength of the immune system; the viral load measures the strength of the virus. Virologic response in older people is comparable to younger.10 However, CD4 counts do not improve as quickly or as much in older patients as in younger.

This is at least partly due to the gradual decline in the function of the thymus, where T-cells are produced, as we age.

Unfortunately, we don’t have good information on older people because they were 26 | J a n u a r y + F e b r u a r y

2011

usually not included in clinical trials of new drugs.

Treatment side effects may not be any more frequent in older people. However, careful research has not been done. Some health changes caused by aging can resemble antiretroviral medication side effects. Other health issues in older people might intensify medication side effects.

For example, older age is a major risk factor for heart disease and for increasing fat in the abdomen. Some older people without HIV lose fat in the face or arms in a way that looks similar to the changes caused by lipodystrophy.

MULTIPLE CHRONIC CONDITIONS As people age, they develop health issues that continue for the rest of their lives.

These chronic conditions can include heart disease, diabetes, depression, osteoporosis, high blood pressure, kidney problems, arthritis, Alzheimer’s disease, and various forms of cancer. As people age, they can become frail. The frailty syndrome is defined as the presence of at least three of the following characteristics: exhaustion, slowed walking speed, low activity level, weakness, and weight loss.11 Older people often take many different medications to deal with their health problems. This makes it more difficult for a doctor to choose anti-HIV drugs because of interactions with other medications. In addition, this “polypharmacy” complicates adherence, especially for people with memory problems or depression.

Many of the health problems of older people appear at younger ages and at higher rates in people with HIV. This has been documented with loss of bone mineral density,12 cardiovascular disease,13 and diabetes.14 However, there is disagreement among researchers about whether HIV causes accelerated aging, or whether the normal diseases of aging interact with each other and HIV and intensify each other. An intriguing possibility was suggested at the recent 1st International

Workshop on HIV & Aging. Mitochondrial damage was proposed as an overall cause for virtually all of the ailments of older age.

The mitochondria are the body’s “power plant,” the source of all energy used by the cells. Mitochondrial damage has been explored in connection with the fat loss of lipodystrophy. It will be interesting to see whether this hypothesis proves true or not.

Older people may have more problems with thinking and remembering than younger people, known as age-related dementia. These symptoms can appear to be the same as HIV-related neurocognitive dysfunction. These problems are less severe than they were before the use of strong anti-HIV drugs. It is difficult to know what is causing mental problems in older people with HIV. Is it normal aging, or is it HIV disease? Research studies have linked both age and higher viral load to mental problems. A large study of central nervous system problems in people with HIV found neurocognitive impairment in 40% of the patients studied.15 Rates of depression and substance use have not been well studied in older people.

However, depression is the second most common psychiatric disorder in HIV populations, after substance abuse.16 These problems may be related to HIV disease, aging, or both. They need to be diagnosed and treated correctly.

LEARNING TO LET GO There’s one way in which we older people with HIV may be ahead of other seniors.

That is in regard to letting go. When we learned of our HIV status, at least if it was more than 15 years ago, we pretty much had to let go of our future. There was no really effective treatment for HIV. Coming out as HIV-positive was always a difficult experience. We experienced some degree of stigma and discrimination. For every friend who would hang in there with us, several couldn’t handle the news. Relationships broke off, sometimes without any explanation. We had to build P o s i t i v e lyAwa r e . c o m

a network of support, if we could. As HIV progressed, we learned to let go of more.

Lipodystrophy, AIDS wasting, or Kaposi’s sarcoma robbed many of their physical appearance. We learned to live with fatigue that took away our ability to ski, or run, or even to walk. Mental capabilities declined, and we figured out a way to compensate.

With aging, we face the same issues. But this time we’re at least somewhat prepared.

A GIFT WITH STRINGS ATTACHED The number of people over 50 with HIV or AIDS is growing rapidly. Life expectancy after a diagnosis of HIV doubled from 1996 to 2005.17 Personally, I have lived over 23 years with HIV, something that certainly did not seem possible when I tested positive. I am grateful for these extra years of life. But they come at a price: twice-daily antiviral medications, with the threat that missing doses could lead to the development of drug resistance. I am dealing with several conditions, including osteoporosis, HIV-related myelopathy (degeneration of the coating of nerve fibers in the spinal cord, though I still haven’t gotten a good explanation of what that is!), high blood pressure, low thyroid—each of which comes with its own medications and limitations.

I walk with a cane, but I’m still here, along with thousands of my colleagues. Many of us have been dealing with HIV and AIDS for over 20 years. We see each other at conferences and appreciate the fact that we are alive to meet once again. I’m 59 years old, and looking forward to more!

Robert Munk, PhD, has been involved in AIDS activism since 1987. He has been a frequent writer and speaker on HIV treatment topics, providing current HIV/AIDS treatment information in non-technical language. Dr. Munk was a founding member of the AIDS Treatment Activists Coalition and currently serves as President of its Board of Directors.

Go to PostivelyAware.com for references.

P o s i t i v e lyAwa r e . c o m

J a n u a r y + F e b r u a r y 2 0 1 1 | 27

BONES OF Contention

Premature aging and bone loss emerge as new concerns with HIV

By Erin N. Marcus, MD

At the age of 56, Jules Levin felt pretty invincible, despite being HIV positive. He went to the gym regularly and controlled his disease well by taking his antiretroviral medicines every day.

Then he slipped one day while on vacation and broke his wrist. He underwent an operation to insert pins in his bones and needed to wear a cast for a month, keep his arm elevated, and then do physical therapy for two months to get to the point where he could lift a five pound weight.

“It was one of the most difficult things I’ve ever been through in my life,” he said. “I ran, biked, lifted weights and now all of a sudden I couldn’t turn the page of a newspaper. It just really got to me.”

After a few simple tests, the reason for Levin’s fracture became clear: His bones were weak from osteoporosis, a disease that’s most commonly seen in older women, but that’s also associated with HIV. “The giddiness of the age of HAART is over,” said Levin, referring to highly active antiretroviral therapy, the life-saving drug regimen prescribed to people with HIV. “We should have an aging clinic in every hospital that’s serving HIV patients.”

Osteoporosis is one of many conditions associated with old age that is now being seen with increasing frequency in people with HIV. Research suggests that long-term exposure to the virus, and to the 28 | J a n u a r y + F e b r u a r y

2011

inflammation it triggers, make people vulnerable to premature aging and to a host of conditions seen with aging, heart and kidney disease, dementia, and osteoporosis.

Additionally, the overall population of people with HIV is getting older, thanks to improved medical therapy. At present, 1 in 4 people with HIV is age 50 or older.

The U.S. Senate Special Committee on Aging has predicted that half of all adults with HIV will be older than 50 by the year 2015. Over the past few years, the National Institutes of Health increased its funding for research on HIV and aging, and the White House hosted a conference on October 27 on HIV and aging.

“The evidence is pretty clear,” said Levin, who directs The National AIDS Treatment Advocacy Project (NATAP), a New York-based HIV education and advocacy group. “We’re going to see early frailty, early senescence and people are going to start dying at earlier ages.”

Compared to other conditions associated with HIV and aging, osteoporosis is relatively straightforward to forestall and treat. To maintain bone strength, it’s important for all people with HIV to make

sure they are consuming an adequate amount of calcium and vitamin D. A recent article in the journal Clinical Infectious Diseases recommends 1,000 to 1,500 mg of calcium and 800 to 1,000 IUs of vitamin D daily, as well as at least 30 minutes of weight-bearing exercise, such as jogging or walking, at least three days a week. Calcium is plentiful in dairy products and sardines, and is available in supplements such as calcium carbonate and calcium citrate. The National Institutes of Health has an online information sheet (http://ods.od.nih.gov/ factsheets/calcium) listing ways to get calcium. It’s also important to avoid smoking and heavy alcohol use, since these can cause osteoporosis.

HIV is thought to be associated with osteoporosis for a variety of reasons.

The infection, itself, causes inflammation, which in turn impacts the cells that maintain bones. Many conditions common in people with HIV, such as vitamin D deficiency, being underweight and low testosterone, are associated with osteoporosis. Antiretroviral therapy and other medications frequently prescribed to people with HIV, such as prednisone, also cause bone loss.

Even though many antiretrovirals can cause bone loss, osteoporosis is not a reason to stop taking them. “Antiretroviral therapy is life-saving, and we know that stopping antiretroviral therapy is not a P o s i t i v e lyAwa r e . c o m

good strategy for preventing complications,” said Dr. Todd Brown, an endocrinology specialist at Johns Hopkins University who co-wrote the article in Clinical Infectious Diseases.

Brown and his coauthors recommend that all HIV-positive men older than age 50 and women who are past menopause undergo testing for osteoporosis, since it’s a condition that usually doesn’t cause symptoms until the person breaks a bone.

His own research has found that osteoporosis is “alarmingly” prevalent among African Americans in inner city Baltimore. “Because of the perception that osteoporosis is a white disease, people of color get short shrift for screening,” he said. “This concept that African Americans are protected shouldn’t be a reason to neglect them.”

Once someone is diagnosed with osteoporosis, it’s important to take action to prevent falling, such as removing clutter and slippery rugs from the floor. Physical therapy can help improve strength and balance, which also reduces the risk of a fall. The person also should get his or her vision checked and review his or her medication list with a doctor to try to minimize

any drug side effects or interactions that might cause drowsiness or unsteadiness.

A class of medicines called bisphosphonates can improve bone strength, but do have some rare risks, Brown said.

“On the flip side, you shouldn’t not use them in the patient who is at high risk of a fracture.”

Levin urges all people with HIV to be assertive about discussing osteoporosis and other age-related conditions with their doctor. “My guess is that 90 percent of patients know nothing about any of this and a lot of clinicians and case managers don’t know about it either,” he said. “Every patient should ask their clinician, if they are monitoring them for heart disease, diabetes, bone disease, cognitive impairment, kidney disease?’ This is an important issue for everybody.” e Erin N. Marcus, M.D., M.P.H. is a general internal medicine physician and associate professor of clinical medicine at the University of Miami Miller School of Medicine.

For the past decade, Dr. Marcus has provided primary care to a mostly low income patient population in inner city Miami. She also

directs a population health curriculum for medical students and is a former member of the National Board of Medical Examiners’ Ambulatory Care test writing committee.

In 2009, Dr. Marcus was one of three physicians nationally to receive an American Cancer Society Cancer Control Career Development Award for Primary Care Physicians. With the support of The Ford Foundation, she writes a practical health column for New America Media (www. newamericamedia.org), the largest association of ethnic media. She is a former American Association for the Advancement of Science Mass Media Fellow and is a fellow of the American College of Physicians. She has served as an author of numerous academic chapters and articles, and her writing has appeared in The New York Times, The Washington Post and the perspective section of the New England Journal of Medicine. Follow Erin N. Marcus, M.D. on Twitter: www.twitter.com/ErinNMarcusMD Similar versions of this article originally appeared on the websites of New America Media and The Huffington Post. Reprinted with permission of the author.

Subscribe or donate. ❑ 1-year subscription: $30. (Subscriptions are mailed free of charge to those who are HIV-positive.)

❑ renewal: $30. Enclosed is my payment. ❑ Back issues: $3 per copy. Enclosed is my payment.

❑

enclosed is my donation of: ❑ $25 ❑ $50 ❑ $100 ❑ $250 ❑ $500 ❑ $_______ Your contribution helps provide subscriptions to people who can’t afford them. All donations are tax-deductible to the full extent allowed by law.

❑ Nov./Dec. 2010: ______ copies ❑ Sept./Oct. 2010: ______ copies ❑ July/August 2010: ______ copies ❑ May/June 2010: ______ copies ❑ March/April 2010: ______ copies ❑ Jan./Feb. 2010: ______ copies

❑

e-mail newsletter: Sign me up for e-mail updates.

My e-mail address

Charge my: ❑ Visa ❑ MasterCard ❑ American Express Total Amount: $___________

❑

BULK COPIES of Positively Aware: No charge; donation requested. Number of copies requested via UPS. (No P.O. Box):

Card Number

______ copies

MAIL TO: Positively Aware

5537 N. Broadway St.

Chicago, IL 60640 P o s i t i v e lyAwa r e . c o m

Name Address City Phone

State

Zip

e-mail

Expires:

Name on Card

Signature (required)

Charges will appear on your credit card bill as TPA Network. Test Positive Aware Network (TPAN) is a not-for-profit organization dedicated to providing support and information to all people impacted by HIV. J a n u a r y + F e b r u a r y 2 0 1 1 | 29

ONE ON ONE

Getting Down

with the

DIVA Interview by Jeff Berry | PHOTOS BY TERRY E. CHRISTANIO

From her role as Deena Jones in the original Broadway production of Dreamgirls, hit television sitcoms including It’s a Living, Moesha, and Designing Women, films such as Sister Act II, The Flintstones, and The Mighty Quinn, to a successful singing career spanning decades, Sheryl Lee Ralph continues to entertain and dazzle audiences and fans around the world with her unique style, beauty, and fierceness. The consummate actor, singer, entertainer, and performer—a diva in every sense of the word—Sheryl Lee Ralph recently sat down to talk with Positively Aware about the other passion in her life, and what it is that keeps her going.

JB: What’s a typical day like for you?

SLR: There’s nothing “typical” about any of my days at all! I travel a lot, I’m a mother, I have two children, I’ve got a husband, I’ve got my passion, I have my foundation, I have my career, and everything is always going at some point in my life. There is nothing typical or ordinary about it at all.

JB: How do you do it? What inspires you to do all the work you do?

SLR: What inspires me is memory. You know, I’m part of the original Broadway company of Dreamgirls and we made our debut back in 1981. The summer of 1981 was when five men presented in hospitals in Los Angeles with a mysterious disease that made everybody say, “What the hell is this?” As we opened, I always say it was one of the best times in my whole life, but 30 | J a n u a r y + F e b r u a r y

2011

in the midst of the greatest times in my life, came the worst. That was when, in the year of 1982, men just started dropping dead up and down Broadway of that mysterious disease that nobody wanted to talk about.

It’s the memory of many friends that I lost to AIDS that keeps me doing the work that I do. I remember when men just got sick and they died, and then there was a deadly silence that fell over their suffering and their deaths and I said, “You know what?

I’ve got to do something to remember my friends.” That’s why I do the work that I do.

JB: What are some of the key issues you hope to address through the work you do?

SLR: We concentrate on erasing stigma, breaking the silence, and of course, getting people to get tested. My husband, Senator Vincent Hughes, and I have P o s i t i v e lyAwa r e . c o m

Stage presence: A show of unity between Sheryl Lee Ralph and friends at the 20th annual Divas benefit in October.

created something called “TestTogether. org” where we encourage couples to go on and get tested together. We say, “Spread love, not disease.” And we’ve taken it even further by telling mothers, “Take your daughters,” and to fathers, “Take your sons.” Normalize testing for this disease so they’re not afraid to do it, so they’re able to make a good choice for themselves when that time comes.

JB: That’s great. I wanted to thank you also for participating in our “A Day with HIV in America” photo campaign.

SLR: Thank you! That happened to work out just perfectly. We were in the midst of planning the 20th DIVAs Simply Singing.

JB: Right! Could you talk a little bit more about that event and how it came to be?

SLR: DIVAs Simply Singing was an idea I had 21 years ago, once again, to carry on the memory of the good friends I had lost as part of that Dreamgirls company.

I said, “Look, any man who could help you with your wig, weave, and wardrobe problems—those are the kind of men who need to be remembered.” So I called up all of my good girlfriends and said, “I know you’ve all lost somebody. Come join me onstage and just sing a song with piano P o s i t i v e lyAwa r e . c o m

alone.” And the reason it was piano alone was that we couldn’t afford anything else. I had a little piece of money that somebody gave me, I put it with my own money, and that year was the very first DIVAs Simply Singing. I had no idea that we would become the longest consecutive-running, musical AIDS benefit in America some 20 years later.

JB: That’s fantastic. Do you have any plans to take it on the road?

SLR: You know what, if the right funding became available, if the right funders said, “Look—we’re ready to take this on the road,” I’d be there in a heartbeat.

JB: Can you tell me a little bit more about the foundation and what “DIVA” stands for? Maybe some other types of programs besides the fundraiser you’re working on?

SLR: Alright. DIVA—Divinely Inspired Victoriously Anointed. DIVA—Divinely Inspired Very AIDS Aware. I created the DIVA foundation because, first of all, I always felt that if sex could be a problem for men, women could not be far behind.

People told me that I was crazy. They told me folks would not like me. They told me that I spend too much time talking about “those” people, what’s wrong with me?

And I realized that if people were thinking that way, there was a lot of work to be done. So I started, once again, really using the Arts to fight the good fight. I was aware that a lot of people were making speeches and other people were doing pamphlets, but I always believed that if we used the Arts, at least we’d get people’s attention. So our first program was, of course, DIVAs Simply Singing. We since moved on to do the Sisters Circle where we incorporate infected and affected women from South Africa and connect them with women from the United States.

Sit, meet, greet, and exchange ideas to see how they can stem the tide of the infection rate within their families, within their communities, within their countries.

I’ve also written a one-woman show called “Sometimes I Cry” and you can see more about that at sometimesicry.org.

“Sometimes I Cry” is all about real women, real stories around HIV and AIDS. In the summer of 2002, I realized that the disease had things that jumped and I thought it might make it from men to women. And a whole lot of women had their own personal HIV stories to tell and nobody was saying anything, nobody was talking about it, it wasn’t on anybody’s radar, nobody was doing anything and that’s when I J a n u a r y + F e b r u a r y 2 0 1 1 | 31

made up my mind. I said, “If no one’s gonna do anything, then someone ought to do something.” So I started collecting all these women’s stories and for the past—my God—almost eight years now, I have been touring the world just performing these women’s stories.

So that’s just some of what we do. We have another project we’re working on called the Bead Project where we work with artisans out of southern Africa, trying to present their beadwork to the rest of the world. If you go to thedivafoundation. org, you can find out about this. I created a line called Red Ribbon Wear and these

are T-shirts where I incorporated the red ribbon, because far too many people have forgotten that the red ribbon stood for us uniting in the fight against HIV and AIDS. A lot of people thought the red ribbon was for heart disease, but I said, “No! I want people to know and start talking about the red ribbon in connection with its origins,” and that was the fight against HIV and AIDS. So we have DIVA with the red ribbon; we’ve got “respect me” with the red ribbon; we’ve got angel’s wings and the red ribbon—anything to get people talking. This disease grows in silence. We’ve got to break the silence.

JB: Absolutely, I agree. So, the South African program—Sisters Circle—what inspired you to do that? Do you have any plans for future projects in that region?

SLR: Well, I’ll tell you, what really made me do it was the rise in infection rates among women of African descent. Whether we were talking about African Americans or black women around the world, it seemed like the infection rate for them was just rising, rising, rising, to nobody’s interest and sometimes, it seemed, not even their own.

And I said, “We’ve got to do something about this!” So I said, “Let me bring the women to the table, let me bring them to

Diva Foundation: 2011 and beyond

W

hile most well-known for her annual fundraising event Divas Simply Singing, which brings together female entertainers such as Chaka Khan, Teena Marie, Patti Labelle, Ledisi and others for an evening of song and inspiration, Sheryl Lee Ralph is also an ardent advocate for the health of women and girls. Currently over half of all HIV infections around the world are among women, and young women of color continue to be one of the most affected populations in the U.S., both in rates of new infections as well as the number of overall AIDSrelated deaths among women. Throughout the history of the epidemic, women have been on the forefront of caring for their loved ones as they coped with the disease, often neglecting to take care of themselves in the process. For women who are dealing with HIV/AIDS on such a personal and intimate level, the stigma that prevails can still be such an immense barrier that many end up suffering in silence, rather than reaching out for the support they need to survive. As a result, the women’s movement against AIDS has lagged a little behind its male counterpart; however, that’s rapidly changing.

Since the beginning, Sheryl Lee Ralph has ensured that The Diva Foundation’s activities place an emphasis on addressing the realities of HIV risk and survival among women in vulnerable communities, whether it be through her one-woman show, Sometimes I Cry, or her famous “No Glove, No Love” women’s luncheons.

This year’s 20th annual Divas Simply Singing AIDS benefit was no exception. Midway through the show, Sheryl invited a group of diverse HIV-positive women, led by AIDS activist Cathy ElliottOlufs, to come onstage to bring the message home about why women need to speak up and participate in making the change they want to see. Ranging in age from their early 20’s through mid-seventies, the group included students, homemakers, professional women (including a registered nurse), HIV activists, grandmothers, and retirees. This unique and touching aspect of the show, which culminated in the women joining hands and declaring “HIV affects us all,” called attention to the disease’s impact 32 | J a n u a r y + F e b r u a r y

2011

on women and set the stage for Diva advisory board members to share The Diva Foundation’s plans for expanding gender-specific HIV programming across the globe in 2011.

Building upon the incredibly powerful Sisters Circle program of 2008 (view the Sisters Circle video at www.thedivafoundation. org), The Diva Foundation in 2011 will initiate an exciting new series of national and international women-focused projects. One of these will be an expansion of the previous Sisters Circle program.

Through strategic partnerships with women-focused organizations such as the U.S. Positive Women’s Network, as well as a number of international partners such as ICW Global (the International Community of Women Living with HIV), the Foundation works to form international technical assistance teams of strong, positive female leaders and their allies who will travel to regions around the globe bringing the Sisters Circle message of support and hope to women in underserved communities; working to develop infrastructures and networks where they did not exist previously; increasing gender equity; decreasing gender violence; and ultimately reducing stigma and saving lives both here and abroad.

Another exciting project is the First Ladies Initiative, focused on addressing HIV/AIDS in the church. The Diva Foundation is partnering with women leaders in predominantly African American faith-based organizations to address HIV stigma and promote leadership among women and girls around overall health, as well as reduce the number of new infections. The leadership training program which will be initiated in key geographic regions and later expanded to other cities and rural communities will incorporate comprehensive training on HIV (including prevention technologies and treatment) as well as other women’s health issues.

In order to make these and other new programs a reality in 2011, Sheryl Lee Ralph invites individuals and organizations to join the “good fight” by supporting The Diva Foundation through donations of money, time, and expertise. More information on how you too can be a Diva is available on the website at www. thedivafoundation.org.

P o s i t i v e lyAwa r e . c o m

NOTE OF DISTINCTION: Sheryl Lee Ralph rehearsing before the Divas benefit.

sit together and talk about this disease.”

In doing so, I was amazed at the kind of conversation folks were having. It was something else, I couldn’t believe it.

about HIV and AIDS, so I commend you on that.

SLR: Thank you very much. It’s hard work, but it’s got to be done.

JB: And future projects?

SLR: Well, we’ve planned to go back in April and I really hope that our funding comes through and we’re able to take groups back and do it once again.

JB: Let’s talk a little about your personal life. You mentioned your husband and you live in L.A. and you have a son and a daughter, is that correct?

SLR: Yes, actually my husband and I are very modern in that we’re bi-coastal. I’m married to State Senator Vincent Hughes of Pennsylvania. He has two children and I have two children and we figured since each of us has been divorced before, that we didn’t want, by re-marrying, further change in the lives of our children. So we both are raising our kids and we commute to see each other.

JB: So that’s funded through the foundation, and then the annual fundraiser generates money that goes back into the foundation?

SLR: The money goes to the foundation and also always to a local AIDS organization. For the past few years we’ve been working with Women Alive, which is, if you can believe this, the only female-driven AIDS organization in L.A. Does that make any sense?

JB: No, I know, it’s…

SLR: It’s RIDICULOUS! There’s a huge need out there and why people aren’t responding…you know, the funds are getting cut and now they’re being marked for deeper cuts and we’re really talking about people’s lives. We were always talking about people’s lives, but it seems like we’re just backsliding, going into the past.

JB: And that’s what makes events and foundations such as yours even more important, especially when people who are celebrities step forward and speak out P o s i t i v e lyAwa r e . c o m

JB: So where will we see Sheryl Lee next?

SLR: You know something? From your mouth to God’s ears. I hope it’s on a big, new show where I talk, where I get to see myself interact with people. That would just be so super.

JB: Wow, that would be wonderful.

SLR: Yeah. I feel it, you know? I’m talking to you now ‘coz I’m on the train back to Philly—I just left CNN, you know, HLN their headline news station where I was doing Show Biz Tonight and it was so great. They were like, “Sheryl Lee Ralph, you were made for this, you were born to just talk to people and talk to them about difficult things and get them to smile at it.”

JB: If people are interested in getting more involved in the work of the foundation or supporting some of these programs, what suggestions would you provide?

SLR: I would ask them to please visit thedivafoundation.org and take a look at what we are doing and if they want to support it, make a donation and we’ll send you one of our red ribbon T-shirts or past performances of DIVAs or something from the Bead Project—there’s a lot out there.

Oh, my gosh, I just love the way that people just love the things that we do. I’ll never forget, on a return trip to Africa, I had left some T-shirts there and when I came back, I was met by a group of women who were all wearing the T-shirts.

One of them came up to me and said, “We are DIVA!” I was like, oh my God, wow. This is the start of something wonderful.

JB: Is there anything else that you wanted to say?

SLR: I just want to encourage everybody to get informed, get the proper information about HIV and AIDS. Get involved. Tell somebody. You never know what it is that people might need that you have to offer.

Another thing is get tested. The number one reason that people don’t tell anyone that they have HIV is that they don’t know.

They haven’t been tested. They don’t know their status.

JB: Great advice. Thank you so much for taking the time to talk.

SLR: You’re very welcome. e J a n u a r y + F e b r u a r y 2 0 1 1 | 33

THE BUZZ Daniel S. Berger, MD

Svelte and sassy

Egrifta gains FDA approval and testosterone remains tried and true There are many hormones that one considers to have important utility within the field of HIV therapeutics. This article will discuss two of them specifically: testosterone, the oldest therapeutic intervention, first used to combat wasting, now administered more often and in more healthy individuals; and Egrifta, the latest hormone recently approved for the treatment of HIVassociated abdominal fat accumulation.

To date, there has been so much information about testosterone that it’s difficult to cover its full particulars and finer points in an article. However, a recent book by Nelson Vergel, “Testosterone, A Man’s Guide,” has excellent detailed information.

In contrast, Egrifta, which is growth hormone releasing factor (GHRF), is the latest hormone making its way into the HIV armamentarium; it has only recently been approved as of November 2010.

The information we know is based mainly on two large Phase 3 trials, in which I am proud to have participated as a lead principal investigator. Its development is historic. As the first and only agent to have gained approval to combat an aspect of lipodystrophy, it has been shown to reduce fat accumulation, also known as visceral hypertrophy, or increased belly fat.

To open this dialogue on these hormones as treatment, it’s important to put them into clinical context. This article will begin with four real cases (the names have been changed) that I’ve recently seen in the exam room at Northstar, which will pose as useful vehicles to illustrate salient points in this article’s discussion.

Case 1 Dustin is a 31-year-old, attractive, healthy guy who is devout in his practice of gay religion: going regularly to the gym (gay 34 | J a n u a r y + F e b r u a r y

2011

church) and healthy eating. Overall, he’s maintaining himself in the best ways and is in great shape. He’s not seen a doctor in years but came into my office because particular issues have been bothering him. He stated that ever since he can remember, he seems to have less of a libido than his friends; when he does meet an attractive “hot” man and finds himself in the “position,” he has a difficult time maintaining an erection, despite feeling sexually aroused. He also has difficulty gaining weight, though he does all the right things—diet, exercise, protein supplements. He does not have fatigue or depression symptoms.

Case 2 Mark is a 54-year-old college professor, not married, but has a girlfriend. Throughout his life he’s been an ardent athlete, staying in shape, but now finds himself with less of a desire to go to the gym. He’s noticed that his libido is down, as well. When discussing these issues with his then primary care physician, the doctor who checked on his testosterone (T) level told him that it was “normal” for his age. He came to my office looking for a second opinion and stating that he didn’t want a testosterone level that was normal for his age, but rather a more normal testosterone level for any age. He wanted to regain that zest for enjoying all

that life has to offer, which has been dropping off recently.

Case 3 Doug is a 37-year-old HIV-positive man who has been well controlled on his antiretroviral cocktail, undetectable, and with good CD4 counts. He has no other significant problems but has noticed that he becomes more tired, even early in the day and upon first getting out of bed in the morning. He also notices that he’s been putting on the wrong kind of weight, more fat and less muscle, despite trying his best to exercise. He mentions that he’s not had much desire for sex, and doesn’t consider this too important, but “wouldn’t mind if things were different.”

Case 4 Mike is HIV-positive and had complaints of low libido, feeling depressed, and fatigue.

His doctor told him his T levels were “normal.” When he pressed his doctor to tell him what his levels were, his previous doctor said that normal levels are between 280 and 900 and that he was within the normal, at 330. Mike nearly freaked, but his doctor continued to reassure him. The other important fact is that Mike has noticed that his waist size has been growing, despite the fact that he’s not changed his diet. His doctor reassured him and explained that he is doing well. Mike confided in me, saying all he could think of was the fact that the only thing normal about himself was that he didn’t have a soprano voice, and hasn’t developed breast tissue, yet. He finally got a second opinion.

Testosterone’s many important functions Testosterone, known as the male sex hormone, is important for many physiologic P o s i t i v e lyAwa r e . c o m

When low testosterone levels persist, a syndrome of hypogonadism can develop and includes symptoms of low libido, fatigue, and depression, very common in HIV disease. and metabolic functions other than simply improving performance in the bedroom.

Low and deficient levels may be associated with fatigue, depression, irritability, bone thinning, and in older individuals, reduced cognitive function. These are in addition to the more well known problems of low libido and erectile dysfunction. The cases above illustrate various scenarios and Case 3 illustrates a patient complaining of constitutional symptoms that are a typical presentation of low testosterone levels (in addition to complaints of low libido). When low testosterone levels persist, a syndrome of hypogonadism can develop and includes symptoms of low libido, fatigue, and depression, very common in HIV disease. In HIV-positive individuals, serious loss of lean body mass is defined as wasting syndrome. Also, low testosterone levels are associated with increased abdominal fat. When wasting occurs in persons with HIV, it is associated with more infections, many constitutional symptoms, and increased risk of death.

Some years ago, we published a study which showed that 25% of individuals with wasting in the era of HAART may have low testosterone levels.

Originally, it was several communityinvolved HIV specialists who began recognizing the importance of testosterone replacement. Back in the early ’90s, we began offering our patients “physiologic replacement” by injection. In other words, we administered doses of testosterone that are consistent with what the body should have to maintain its normal levels and function. This led to a much-improved sense of well-being among our patients and the reduced potential for weight loss and other HIV complications. Eventually, several companies developed testosterone products in the form of gels and studied their use in HIV-negative men. Lo and behold, there is a large prevalence of men who have low levels and who derive benefits from replacement treatment. I occasionally see young men in their 20s and 30s who have a deficiency, never mind that they are P o s i t i v e lyAwa r e . c o m

HIV-negative. The patient of Case 1 is not an uncommon phenomenon.

Although blood levels of testosterone are checked by physicians, many do not understand that these numeric values are relative, because there is a wide range of normal quoted by each lab. An individual may have a value in the normal range, but it may not be normal for him, since first, he’s developed symptoms. Second, previous levels are not always available to compare. The individuals in Cases 2 and 3 demonstrate that levels may not correlate with symptomatology.

There are two ways that testosterone can be administered: intramuscular injection and topical administration in either gel or cream form. By either route, the replacement of testosterone, from my experience, can show dramatic effects.

These include a marked improvement in energy levels, reduced anxiety and depression symptoms, improved libido and self-confidence, improved stamina, and in the gym, individuals note their improvement in body mass and reduction in fat. Overall, there’s a greatly improved sense of well-being.

A common side effect is increased red blood cell production (hematopoiesis), which we treat at Northstar with therapeutic phlebotomy and sometimes need to modify dosing. Other side effects, such as increased blood pressure, elevated hepatic transaminases (or increased liver enzyme levels), gynecomastia (overdevelopment of a male’s breasts), acne or skin outbreaks, increased appetite, and mood swings can also occur. Thus, monitoring of side effects is important and includes vigilant blood testing for liver enzymes, blood count, blood pressure, testosterone levels, and prostate specific antigen levels. Side effects get detected early and can be easily managed.

There has been concern that testosterone replacement may have a causal relationship to prostate cancer. This has long been a myth that is unfounded. Several clinical studies have now been consistent

in showing that in men who do develop prostate cancer, lower testosterone levels are associated with a more aggressive cancer; another study demonstrated that testosterone levels did not result in increased levels of prostate specific antigen (PSA), a marker used for the early detection of prostate cancer. It is believed, however, that only if there is untreated prostate cancer already present, then testosterone administration may stimulate tumor growth, or worsening of the cancer. Therefore, for patients without prostate cancer, there is no evidence or data that shows testosterone causes cancer. Several urologists agree that there is no danger in administering testosterone in patients who were treated for prostate cancer by prostatectomy.

Patients receiving injections are often on testosterone cypionate (Depo-Testosterone) and are on various intervals of treatment and at varying doses. In the injectable form, the intervals and dosing are often chosen based on the perceived durability of effect by the patient. In other words, the patient will often tell me that at a certain point in time after their injection, they begin to feel its effects wearing off. With each administered injection, there is a surge of testosterone in the blood that occurs promptly. This surge is associated with individuals feeling great relief from their symptoms of deficiency. However, sometimes testosterone levels in the blood may begin to drop off rapidly after a few weeks and sometimes within only a few days of the injection, and can remain low until the next injection. Additionally, the surge in testosterone levels can stimulate the brain’s biofeedback mechanism, and sensing the high testosterone levels, it sends a message to the adrenals and testes to shut down its own endogenous production, sometimes making it difficult to maintain normal levels.

Nevertheless, patients receiving intramuscular injections of testosterone derive very quick relief of symptoms and often prefer this mode of replacement.

Another mode of administration is J a n u a r y + F e b r u a r y 2 0 1 1 | 35

The development of Egrifta is an important milestone in HIV therapeutics. It provides patients an option to combat visceral adiposity and body image issues. by transdermal or topical gel or cream.

Individuals usually apply the gel to an area of skin every morning and thus, testosterone is absorbed gradually over several hours. This daily therapy often leads to more consistent blood levels that avoid up and down symptoms that are associated with injectable replacement. Two such products are available: Androgel and Testim. Both products are applied similarly.

What differentiates them is that the Testim formulation contains a delivery system that allows for higher levels of testosterone absorption and has made it a more efficient replacement overall. The delivery system is a compound that gives Testim a musky aroma, not unlike a musky cologne such as Brut, that dissipates over the course of a few hours. It is my experience that patients often achieve higher levels with Testim.

Additionally, individuals who don’t achieve normal testosterone levels with Androgel often respond better with Testim.

Egrifta, much anticipated, newly approved It’s long been understood that HIV-positive individuals are prone to develop unusual increases of fat in specific parts of their bodies. Until only recently, there was no product approved for its treatment, nor was it clear about what could be done about it.

Egrifta, developed by the Canadian firm Theratechnologies, Inc., is also known as tesamorelin or growth hormone releasing factor. It works by stimulating the body’s own production of growth hormone and leads to oxidation or burning of body fat, specifically visceral or abdominal fat associated with HIV disease, one component that makes up the syndrome of lipodystophy.

Certain medications including the older protease inhibitors such as Crixivan (indinavir) and Kaletra (lopinavir/ritonavir), as well as the non-nuke Sustiva (also a component of Atripla), have been shown in studies to be associated with developing abnormal body fat increases. Some 36 | J a n u a r y + F e b r u a r y

2011

older nucleosides, such as d4T (Zerit or stavudine) and AZT (Retrovir or zidovudine), are also shown to be associated with abnormal body fat changes, most often fat loss or lipoatrophy. These agents reduce mitochondrial functioning. Fat tissue is rich in mitochondria, which are cellular organs known as metabolic powerhouses.

It is also believed that HIV infection itself can cause the fat and body habitus (body type) changes of lipodystrophy. Egrifta, which will be marketed by EMD Serono in the U.S., will no doubt become a very important product used for this purpose.

What we can expect of treatment with Egrifta is a decrease in visceral fat by up to 18%. This effect is indeed significant and easily noticeable by patients whom I was seeing as they participated in the clinical trials. I think that when exercise and diet is combined with Egrifta use, the loss of abdominal fat will only be heightened.

Additionally, from what I personally observed in the exam room during both trials, patients who had low self-esteem from their perceived unsightly appearance and body image became less depressed with treatment. Patients will need to self-administer Egrifta daily by subcutaneous injection.

Patients often notice their body habitus changes long before their physicians. Case 4 illustrates how a patient brings it up in the exam room. One doesn’t need to wait until the lipohypertrophy is severe. If the problem is beginning to manifest itself, I believe one can be proactive and consider treatment early to avert worsening of the condition.

Regarding side effects, Egrifta was generally well tolerated, but because it is associated with increased levels of insulinlike growth factor, side effects include mild stiffness of joints, mild swelling of hands or feet, injection site reactions (redness or tenderness at the injection site), and there is a slight possibility of reduced or impaired glucose tolerance. However, patients with mild diet-controlled diabetes did not have worsening glucose levels during the clinical trials. Nevertheless,

physicians should monitor their patients on treatment, as appropriate.

Conclusion The development of Egrifta is an important milestone in HIV therapeutics. It provides patients an option to combat visceral adiposity and body image issues. Facial wasting is a different manifestation of lipodystrophy that has already been overcome by effective treatment with Sculptra and Radiesse, which are widely administered at Northstar in Chicago and other clinics nationally. Thus, together we have a more rounded line of therapy for various manifestations of lipodystrophy and the psychological ramifications of altered body image. However, dietary measures and exercise should not be overlooked.

In contrast, testosterone deficiency is common among HIV-positive individuals and is associated with many daily symptoms. Replacement treatment improves quality of life through improving daily energy levels, reducing depression, and helps build body mass, strength, and improved cognitive function, in addition to its effect on libido. Testosterone treatment has been used by physicians for many years.

With mounting evidence of its benefits, it is hoped that other physicians who have been reluctant to provide hormonal replacement may feel more comfortable with its management and safety. As patients are increasingly living longer, healthier lives, they can be empowered with the knowledge of the various treatment modalities, realize their therapeutic options, and help themselves achieve an improved quality of life.

Dr. Daniel S. Berger is a leading HIV physician in the U.S. and is Clinical Associate Professor of Medicine at the University of Illinois at Chicago. He is founder and medical director of Northstar Healthcare in Chicago and has been published in such journals as The Lancet and the New England Journal of Medicine. Dr. Berger can be reached at DSBergerMD@aol.com and www.Nstarmedical.com.

P o s i t i v e lyAwa r e . c o m

WHolistic picture Sue Saltmarsh

Ode to control freaks Over the years, I have heard many HIV-positive people tell stories about how they were shocked when they got their HIV diagnosis—one friend described it as instantly feeling like he was in suspended animation, like as long as he didn’t move or speak or even breathe, he might be OK. Others have told me they “always knew” it was possible because of choices that they’d made, but did not regret. Some have approached it with an attitude of “what did I expect with all I was doing?” But, even from those who contracted it through accidental means, I have rarely heard the kind of fathomless “Why ME?!?!” that was my reaction to hearing I am diabetic and which I know frequently accompanies other kinds of diagnoses.

Is that just because HIV-positive people are more “resigned to their fate” than the rest of us? Having witnessed the courage and fight of some long-term survivors, I can’t buy that. Is it because they somehow think they “deserve” it, internalizing the shame and stigma that is too often present around them? While I suppose that’s possible, I hate to think so. Perhaps it’s because many of them felt “out of control” before their diagnosis and now have a reason to reign it in. Yeah, sure—everyone wants to be more inhibited!

But when you consider the need for control that HIV imposes, maybe there’s some truth to that. And if an HIV-positive person is later diagnosed with diabetes, that need for control becomes even greater.

I can’t begin to imagine keeping track of my T-cell count, my viral load, and my cholesterol levels as most HIV-positive people do and then having to add the nagging monitoring of blood sugar and the constant, irrevocable limitations on P o s i t i v e lyAwa r e . c o m

food that diabetics deal with. Knowing how I sometimes grieve those things that have been “taken away” from my life, I can’t imagine the chasm-full of lost joys and freedoms that being HIV-positive and diabetic at the same time results in.

The basic joys and pleasures of human life are reduced to risk assessment. Do you only chose sex partners who are also positive and even then use a condom?

Do you limit your sexual activity to only those things that are “safe?” Can you ever again ride that wave of thoughtless, spontaneous passion that led to torn clothes scattered across the floor and may have brought you to the world of viral load numbers and T-cell counts to begin with?

And then, after the kaleidoscope of sexual possibilities has been narrowed and dimmed (but not extinguished!), let’s consider the topic of food. Food, which, unlike sex, you cannot live without and yet, which now poses its own threats. Do you resign yourself to never enjoying that blissful melt

of chocolate on your tongue without it being followed by the acrid tang of artificial sweetener? Can you ever really enjoy that movie popcorn again without visualizing your blood sugar cutting off circulation to your eyeballs? Will you ever again be able to experience the simple joy of grabbing something out of the refrigerator because you want it without thinking about the sting of the lancet and the beep of the glucose meter two hours later?

As you sit in the doctor’s office every three months, what will you dread most— the viral load or the A1C? Even if you have exercised steel-belted control, even if you’ve been 100% “good,” just the stress of exerting that much control could be enough to drive either, or both, numbers up, no matter how compliant you were with your meds or how low-carb your food was.

Not only do you lose joy and freedom, but those around you see you becoming OCD about the condoms or the sugar-free “treats” (bleck), tired and/or depressed from the limitations, and suddenly they’re not having fun either. It sucks. It’s not fair.

But considering all the limitations, requirements, compromises, and deprivations that most humans live with, perhaps the thing to focus on is that we are indeed living and we have the right and the power to control not only our illnesses, but the way that control affects us. So here’s to all the reluctant control-freaks-by-necessity out there. May your viral load be undetectable and your A1C under 6.

Breathe deep (no carbs), live long.

J a n u a r y + F e b r u a r y 2 0 1 1 | 37