Plus 2020 Treatment Guide

JOSHUA COLEMAN ON UNSPLASH

OUR 8TH ANNUAL HIV TREATMENT GUIDE

JOSHUA COLEMAN ON UNSPLASH

A RUNDOWN OF THE MOST COMMONLY-PRESCRIBED MEDICATIONS APPROVED BY THE U.S. FOOD AND DRUG ADMINISTRATION FOR THE TREATMENT OF HIV AND ITS RELATED CONDITIONS. RESEARCH BY JACOB ANDERSON-MINSHALL, DAVID ARTAVIA, DESIRÉE GUERRERO, AND TRUDY RING Editor’s note: This info was culled from the National Institutes of Health’s drug database, the FDA, and individual pharmaceutical companies.

Unless otherwise noted, all dosages are traditional adult dose.

Atripla generic name: efavirenz, emtricitabine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For adults and children 12 years and older weighing at least 40 kg as an initial regimen. Should not be used for those with moderate or severe kidney or liver impairment, those with neuropsychiatric issues, or women who are pregnant or may become pregnant. traditional dosage: One tablet once daily. Tablet contains 600 mg efavirenz (Sustiva, a NNRTI), 200 mg emtricitabine (Emtriva, a NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, a NRTI).

Biktarvy generic name: bictegravir,

emtricitabine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (less than 50 copies per mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known resistance to the components of Biktarvy. Not recommended for those with creatinine clearance below 30 mL per minute, those with hepatitis B, or those with severe liver impairment. traditional dosage: One tablet once daily. Tablet includes 50 mg of bictegravir (an INSTI), 200 mg of emtricitabine (Emtriva, a NRTI), and 25 mg of tenofovir alafenamide (a NRTI). Doesn’t need to be taken with other HIV drugs.

Cimduo generic name: lamivudine and

tenofovir disoproxil fumarate class of drug: combination of two nucleoside reverse transcriptase inhibitors maker: Mylan who is it for? For adults and children weighing at least 35 kg. Should not be used

for those with creatinine clearance below 30 mL per minute or those on dialysis. traditional dosage: One tablet once daily in combination with other antiretrovirals. Tablet contains 300 mg lamivudine (Epivir/3TC) and 300 mg tenofovir disoproxil fumarate (Viread).

Complera

traditional dosage: One tablet

per day in combination with other antiretrovirals. Each tablet contains 200 mg emtricitabine (Emtriva) and 25 mg tenofovir alafenamide (TAF).

Dovato generic name: dolutegravir and lamivudine

generic name: emtricitabine,

rilpivirine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For those 12 and older who are new to antiretroviral drugs who have viral loads of 100,000 copies per mL or less; or as a replacement regimen for individuals with a viral load of 50 copies per mL or less and no resistance to any components. Use caution if also positive for hepatitis B. traditional dosage: One tablet once daily. Tablet includes 25 mg rilpivirine (Edurant, an NNRTI), 200 mg emtricitabine (Emtriva, a NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, a NRTI).

Delstrigo generic name: doravirine, lamivudine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Merck who is it for? For adults new to HIV medication. Not recommended for those with creatinine clearance below 50 mL per minute and should not be used by those with moderate to severe kidney impairment or severe liver impairment. traditional dosage: One tablet once daily. Tablet contains 100 mg doravirine (Pifeltro, a NNRTI), 300 mg lamivudine (Epivir, a NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, a NRTI).

Descovy generic name: emtricitabine and

tenofovir alafenamide class of drug: two nucleoside reverse transcriptase inhibitors maker: Gilead Sciences who is it for? For adults and children who weigh at least 35 kg, as well as for children who weigh 25 to 34 kg when used with certain other antiretrovirals. Should not be used for those with creatinine clearance below 30 mL per minute or those on dialysis.

class of drug single-tablet regimen maker: ViiV Healthcare who is it for? For adults new to HIV

medication. Not recommended for those with severe liver impairment. traditional dosage: One tablet per day. Each tablet contains 50 mg dolutegravir (Tivicay, an II) and 300 mg lamivudine (Epivir, an NRTI).

Edurant generic name: rilpivirine class of drug: non-nucleoside reverse transcriptase inhibitor maker: Janssen who is it for? For treatment of HIV-1 in adults and children 12 and older weighing at least 35 kg who haven’t previously taken antiretroviral drugs and have a viral load of 100,000 copies per mL or less. traditional dosage: One 25 mg tablet once daily with meal. It is always taken with other antiretrovirals. Is also a component in single-tablet regimens Complera, Odefsey, and Juluca.

Emtriva generic name: emtricitabine class of drug: nucleoside reverse

transcriptase inhibitor maker: Gilead Sciences who is it for? For adults and children as a component of an initial regimen.

Dosing needs to be adjusted for those with decreased kidney function. Use caution if also positive for hepatitis B. traditional dosage: One 200 mg capsule once daily.

Epivir generic name: lamivudine or 3TC class of drug: nucleoside reverse transcriptase inhibitor maker: ViiV Healthcare

who is it for? For adults and children

at least 3 months old, as a component of an initial regimen. Dosing needs to be adjusted for those with decreased kidney function. traditional dosage: One 300 mg tablet once daily, or one 150 mg tablet twice daily.

Epzicom generic name: abacavir sulfate and lamivudine

class of drug: two nucleoside reverse

transcriptase inhibitors maker: ViiV Healthcare who is it for? For adults and children weighing 25 kg or more as a component of an initial regimen. Not recommended for those with decreased kidney function. traditional dosage: One tablet once daily. Tablet contains 600 mg abacavir sulfate (Ziagen) and 300 mg lamivudine (Epivir).

Evotaz generic name: atazanavir and cobicistat

class of drug: a protease inhibitor and

drug resistance to the components of Genvoya. Not recommended for those who have a creatinine clearance below 30 mL per minute. traditional dosage: One tablet once daily. Tablet contains 150 mg of elvitegravir (an INSTI), 150 mg cobicistat (Tybost, a PKE), 200 mg emtricitabine (Emtriva, a NRTI), and 10 mg tenofovir alafenamide (a NRTI).

Intelence generic name: etravirine class of drug: non-nucleoside reverse

transcriptase inhibitor maker: Janssen who is it for? For treatmentexperienced HIV-1 patients with viral strains resistant to an NNRTI and other antiretroviral agents. For adults, children 6 years or older weighing at least 16 kg. traditional dosage: One 200 mg tablet (or two 100 mg tablets) twice daily following meal. Pediatric patients (6-18 years old) should be dosed by medical professionals based on body weight.

Isentress

a pharmacokinetic enhancer/booster maker: Bristol-Myers Squibb who is it for? For those initiating treatment as a component of a regimen.

Not recommended for those with liver impairment. Use with caution if you have heart or kidney problems; diabetes; hemophilia; or are pregnant, plan to become pregnant, or are using hormonal birth control. Do not breastfeed. traditional dosage: One tablet once daily, in combination with other antiretroviral drugs. Tablet includs 300 mg atazanavir (Reyataz, a PI) and 150 mg cobicistat (Tybost, a PKE).

generic name: raltegravir class of drug: integrase inhibitor maker: Merck who is it for? For those new to

Genvoya

Juluca

generic name: elvitegravir, cobicistat,

generic name: dolutegravir and

emtricitabine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For those 12 or older who weigh at least 35 kg and are new to antiretroviral therapy; or as replacement therapy for those virologically suppressed for at least six months, with no previous virologic failure, and no

treatment or treatment experienced, as a component of a regimen. For adults and children weighing at least 2 kg. Tell your doctor if you have tuberculosis, or liver problems or phenylketonuria. traditional dosage: One 400 mg tablet twice daily for those with treatment experience. Those new to treatment or with undetectable viral loads may either take one 400 mg tablet twice daily or two 600 mg tablets once daily.

rilpivirine

class of drug: single-tablet regimen who is it for? For adults who are virally suppressed for at least six months. maker: ViiV Healthcare traditional dosage: One tablet once daily, with a meal. Each tablet contains 50 mg dolutegravir (Tivicay, an II) and 25 mg rilpivirine (Edurant, a NRTI).

Norvir generic name: ritonavir class of drug: protease inhibitor maker: AbbVie who is it for? For adults and children,

used only in combination with other antiretrovirals, as a component of initial regimen. Reduced dosage recommended for people taking other protease inhibitors. traditional dosage: Six 100 mg tablets taken twice daily.

Odefsey generic name: emtricitabine,

rilpivirine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For adults and children 12 years and older weighing at least 35 kg who are new to antiretroviral drugs, who have a viral load of 100,000 copies per mL or less; or can be used as a replacement regimen for individuals with a viral load of 50 copies per mL or less, who have been virologically-suppressed for at least six months. traditional dosage: One tablet once daily. Tablet conains 200 mg of emtricitabine (Emtriva, a NRTI), 25 mg of rilpivirine (Edurant, a NNRTI), and 25 mg of tenofovir alafenamide (a NRTI).

Pifeltro generic name: doravirine class of drug: nonnucleoside reverse

transcriptase inhibitor maker: Merck who is it for? For adults as part of an initial regimen. traditional dosage: One tablet, 300 mg, once daily, taken in combination with other antiretrovirals.

Prezcobix generic name: darunavir and cobicistat class of drug: protease inhibitor and a pharmacokinetic enhancer/booster maker: Janssen who is it for?:For both treatmentnaive and treatment-experienced adults with no darunavir-related resistance.

Should be used in combination with other

antiretroviral medicines. Use with caution if you have liver or kidney problems; or if you are pregnant, breastfeeding, or plan to become pregnant. traditional dosage: One tablet once daily with food. Tablet contains 800 mg of darunavir (Prezista, a PI) and 150 mg of cobicistat (Tybost, a PKE).

Prezista generic name: darunavir class of drug: protease inhibitor maker: Janssen who is it for? For treatment of HIV-1,

both those initiating treatment and those who have previously been on antiretroviral therapy, including those with some drug resistance to PIs. For adults and children 3 years or older weighing at least 10 kg. May reduce effectiveness of birth control pills. traditional dosage: One 800 mg tablet once daily with 100 mg Norvir or 150 mg Tybost for those without resistance. One 600 mg tablet with 100 mg Norvir taken twice daily for pregnant women and those with Prezista-related resistance. Must be taken with a booster like Norvir or Tybost. Pediatric patients (3 years to less than 18 years old and weighing at least 10 kg) should be dosed by a medical professional based on body weight. Should always be taken with food.

Reyataz generic name: atazanavir class of drug: protease inhibitor maker: Bristol-Myers Squibb who is it for? For both treatment naive

and treatment-experienced individuals. traditional dosage: 300 mg capsule, taken with 100 mg of Norvir or 150 mg Tybost, once daily.

Selzentry generic name: maraviroc class of drug: entry inhibitor maker: ViiV Healthcare who is it for? For the treatment of

only CCR5-tropic HIV-1 infection in adults and children 2 years or older, weighing at least 10 kg, and having a creatinine clearance of at least 30 mL per minute.

Not recommended as a component of an initial regimen. Tell your doctor if you have heart or kidney problems, or if you have

low blood pressure or take medication to lower it. traditional dosage: 300 mg twice daily; or 150 mg twice daily if taken with CYP3A inhibitors; or 600 mg twice daily if taken with CYP3A inducers.

Stribild generic name: elvitegravir, cobicistat,

emtricitabine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For those 12 or older, who weigh at least 35 kg, and are new to antiretroviral therapy; or as a replacement regimen for those virologically suppressed on their current regimen for at least six months, who have no previous virologic failures, and no drug resistance to Stribild components.

Not recommended for those with a creatinine clearance below 70 mL per minute or for those with severe liver problems, or during pregnancy. traditional dosage: One tablet once daily. Tablet contains 150 mg of elvitegravir (a INSTI), 150 mg cobicistat (Tybost, a PKE), 200 mg emtricitabine (Emtriva, a NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, a NRTI).

Sustiva generic name: efavirenz class of drug: nonnucleoside reverse

transcriptase inhibitor maker: Bristol-Myers Squibb who is it for? For adults and children 3 months and older weighing at least 3.5 kg as a component of initial regimen. Tell your doctor if you have had hepatitis or other liver problems, mental illness, or seizures. traditional dosage: One tablet of 600 mg once daily. It is also a component in the single-tablet regimen Atripla.

Symfi/Symfi Lo generic name: efavirenz, lamivudine,

and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Mylan who is it for? For adults and children weighing at least 40 kg (those weighing at least 35 kg can take Symfi Lo).

traditional dosage: One tablet, once

daily, on an empty stomach. Symfi contains 600 mg efavirenz (Sustiva, an NNRTI), 300 mg lamivudine (Epivir, a NRTI) and and 300 mg tenofovir disoproxil fumarate (Viread, a NRTI). Symfi Lo contains 400 mg efavirenz, 300 mg lamivudine, and 300 mg TDF.

Symtuza generic name: darunavir, cobicistat,

emtricitabine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Janssen who is it for? For treatment-naïve or those with a suppressed viral load on a stable HIV regimen for at least six months with no known resistance to darunavir or TAF. Not for those with severe liver or kidney impairment. traditional dosage: One tablet, once daily, with food. Each tablet contains 800 mg darunavir (Prezista, a protease inhibitor), 150 mg cobicistat (Tybost, a PKE), 200 mg emtricitabine (Emtriva, a NRTI), and 10 mg TAF (a NRTI).

Temixys generic name: lamivudine and

tenofovir disoproxil fumarate class of drug: Two nucleoside reverse transcriptase inhibitors. maker: Celltrion who is it for? For adults and children weighing at least 35 kg as component of an initial regimen. Not recommended for patients with impaired kidney function.

Patients should be tested for hepatitis B before beginning treatment. traditional dosage: One tablet once daily. Contains 300 mg lamivudine (Epivir) and 300 mg TDF.

Tivicay generic name: dolutegravir class of drug: integrase inhibitor maker: GlaxoSmithKline who is it for? For both those new to

treatment and those who have taken integrase inhibitors previously and may have resistance to such drugs. For adults and children at least 30 kg. Take during pregnancy only if potential benefits outweigh risk. traditional dosage: One 50 mg tablet, once daily for those new to

antiretrovirals; twice daily for those who take certain other antiretrovirals or have taken integrase inhibitors and may have resistance.

Triumeq

emtricitabine (Emtriva) and 300 mg tenofovir disoproxil fumarate (Viread). for hiv prevention: One tablet once daily. Must be paired with regular HIV tests and safer sex practices.

Tybost generic name: abacavir sulfate,

dolutegravir, and lamivudine class of drug: single- tablet regimen maker: ViiV Healthcare who is it for? For adults and children weighing at least 40 kg as initial regimen.

Not recommended for those with a creatinine clearance below 50 mL per minute or those with liver impairment. traditional dosage: One tablet once daily. Tablet contains 600 mg abacavir sulfate (Ziagen, a NRTI), 50 mg dolutegravir (Tivicay, an INSTI), and 300 mg lamivudine (Epivir, a NRTI).

Trogarzo

generic name: cobicistat class of drug: pharmacokinetic enhancer/CYP3A inhibitor/ booster who is it for? For adults taking atazanavir (Reyataz) or darunavir (Prezista). Tybost is not an HIV medicine and does not treat HIV: it interferes with the breakdown of these HIV drugs, increasing the blood levels of these drugs and making them more effective. maker: Gilead Sciences traditional dosage: One 150 mg tablet daily with food, with either 300 mg atazanavir or 800 mg darunavir.

Viread generic name: ibalizumab class of drug: post-attachment inhibitor

maker: Theratechnologies

who is it for? For heavily treatmentexperienced adults with multidrug resistant HIV-1 infection who are failing their current antiretroviral regimen, as a component of a regimen. traditional dosage: A loading dose of 2,000 mg, administered as an injection, followed by a maintenance dose of 800 mg every two weeks.

generic name: tenofovir disoproxil fumarate

class of drug: nucleoside reverse

Truvada

transcriptase inhibitor maker: Gilead Sciences who is it for? For adults and children at least 2 years old and weighing at least 10 kg, used in combination with other antiretrovirals to treat HIV-1 infection.

Dosage adjustments recommended for those with kidney problems. traditional dosage: One 300 mg tablet once daily.

generic name: emtricitabine and

Ziagen

tenofovir disoproxil fumarate class of drug: two nucleoside reverse transcriptase inhibitors maker: Gilead Sciences who is it for? For those with HIV or at high risk of becoming HIV-positive. As treatment for HIV, for adults and children weighing at least 17 kg. As HIV prevention, for adults and and adolescents 15 or older weighing at least 35 kg. Dosing adjustments necessary for those with decreased kidney function. for hiv treatment: One tablet once daily, in combination with other HIV medications. Tablet includes 200 mg

generic name: abacavir class of drug: nucleoside reverse transcriptase inhibitor maker: GlaxoSmithKline who is it for? For adults and children at least 3 months old, as a component of initial regimen. Dosage adjustments not needed for those with kidney problems. traditional dosage: One 300 mg twice daily or two 300 mg once daily.

Individuals with mild liver impairment should take 200 mg twice daily.

2021 AND BEYOND:

COMING SOON HIV DRUGS UNDER DEVELOPMENT OFFER VARIOUS NEW PATHWAYS TO TREATMENT OR PREVENTION. BY PLUS EDITORS

HIV drugs in the pipeline represent a variety of approaches to attacking the virus, and some are focused on eliminating the reservoir of latent HIV that remains even when the virus has become undetectable. Treating HIV in patients who have developed resistance to other drugs is another priority, as are long-lasting treatments and preventive drugs for people who find it troublesome to take a pill every day (some are injectable). Some of these new drugs have potential to be used in both treatment and prevention. Here’s a look at meds expected to be available in the near future or a little further down the pike.

EXPECTED TO BE APPROVED IN 2020:

CABENUVA: Consisting of ViiV Healthcare’s integrase inhibitor cabotegravir and Janssen’s NNRTI rilpivirine, this once-monthly injectable was rejected by the Food and Drug Administration last December, not due to safety or efficacy problems, but because of concerns about the manufacturing process. ViiV Healthcare officials have said they will work closely with the FDA to determine the next steps for another application. The treatment was approved in Canada in March. Clinical trials used a cabotegravir injection of 400 mg and a 600 mg rilpivirine injection.

The dose consisted of two 2-mL injections. While oral rilpivirine must be taken with food, this injectable does not. Vocabria, a tablet form of cabotegravir, was also approved in Canada and is to be used for brief periods in conjunction with oral rilpivirine (Edurant) to assess how the injectable regimen will be tolerated and as a bridging therapy for missed injections.

FOSTEMSAVIR: ViiV Healthcare applied for FDA approval of Fostemsavir in December. It is recommended for treatment-experienced patients with a history of drug resistance. It’s the first drug in a new class called attachment inhibitors.

It works by binding directly to a protein on the surface of HIV and prevents the virus from attaching to immune cells; therefore HIV can’t infect the cells or multiply. It is a prodrug, meaning it’s an inactive drug. Once taken, it does not work until the body converts it into an active form. In the body, fostemsavir is converted to temsavir. In clinical trials, participants took the drug after eating and in combination with one or more other antiretrovirals. A Phase III study, the BRIGHTE trial, found that fostemsavir helped decrease the amount of HIV in patients’ bodies. It has not been studied in treatment-naive patients, pregnant women, or people under age 18.

“Fostemsavir may provide an important treatment option for the group of people living with HIV who, for a variety of reasons, are not able to suppress their virus with other medicines and could be left with few or no treatments available to them,” says Viiv Healthcare CEO Deborah Waterhouse.

LERONLIMAB (PRO 140): CytoDyn’s HIV treatment would be the first in a new class of therapeutics called viral-entry inhibitors and the first self-injectable subcutaneous HIV drug. It works by masking CCR5, thus inhibiting HIV’s ability to enter healthy T cells. A Phase III trial involving treatment-experienced patients showed that in combination with other antiretroviral drugs, it helped 81 percent of participants achieve significant viral suppression (less than 50 copies per mL), a higher percentage than with other drugs recently approved. CytoDyn has submitted the first part of its application for FDA approval of Leronlimab and is working on the other two sections. The drug is also being studied for use as a treatment for COVID-19 and for nonalcoholic steatohepatitis, a chronic liver disease.

PGT121: A small study showed that an experimental monoclonal antibody called PGT121 led to viral suppression that lasted for up to six months in HIV-positive people who started with a low viral load. Being developed by a collaboration that includes the International AIDS Vaccine Initiative, the Bill & Melinda Gates Foundation, the Scripps Institute, and Theraclone Science, the recombinant monoclonal antibody targets the V3 glycan site on the outer envelope of HIV. At the 2019 Conference on Retroviruses and Opportunistic Infections, researchers reported that two participants with low viral loads experienced treatment-free viral suppression, which for one lasted over five months and for the other was still ongoing at six months.

PGT121 could eventually become a very long-acting HIV medication or a functional cure that maintains viral suppression after antiretroviral therapy has ended.

UB-421: In a Phase II trial, this broadly neutralizing antibody targeting domain 1 of CD4 was shown to maintain viral suppression after treatment ended.

Weekly or biweekly intravenous infusions of UB-421 kept the viral loads of all 29 participants suppressed after they stopped taking oral HIV meds. Research is continuing into the antibody’s potential as a functional cure as well as its efficacy in patients with multidrug-resistant HIV. GS-6207: Developed by Gilead Sciences, this firstin-class long-acting capsid inhibitor interferes with the transport of the viral genetic material and replication of HIV’s genetic blueprint into a host cell’s nucleus. It is given subcutaneously. At this year’s CROI, researchers reported efficacy of injections lasting 10 days. The early trials show the drug has potential as a long-acting treatment for HIV, including for people who have developed resistance to multiple drug classes and those who are unable to take a daily pill. Researchers will now study the effects of GS-6207 on people who have been taking Biktarvy. They also said it will be worthwhile to evaluate the drug in ongoing Phase II trials, for both treatment-naive and treatment-experienced patients, with an injection every six months.

LEFITOLIMOD: Lefitolimod is a type of latencyreversing agent called a toll-like receptor 9 agonist—toll-like receptors, or TLRs, are proteins that help the immune system recognize dangers, and agonists are used to enhance this activity.

Researchers believe lefitolimod may improve the body’s immune response to HIV in addition to its effect on latent virus cells. Researchers in Denmark tested lefitolimod in the TEACH study, which showed it to be safe in early-phase trials.

A Phase IIa study, TITAN, began in November at Denmark’s Aarhaus University, in which patients on antiretroviral treatment are being given Lefitolimod along with virus-neutralizing antibodies developed

by Rockefeller University to see if the therapy can reduce the viral reservoir. Lefitolimod was

developed by German company Mologen, and the TITAN study is being funded

by Gilead Sciences. The study is expected to wrap up next year.

VESATOLIMOD (GS-9620 AND GS-986): These are also TLR agonists, targeting receptor 7 (researchers have identified at least 10 such receptors in humans), and likewise aimed at reducing or eliminating viral reservoirs, which remain even in people who have achieved viral suppression and are an obstacle to curing HIV. At CROI 2020, Gilead Sciences’s toll-like receptor 7 agonist (TLR7 )—an agonist is a chemical that binds to a receptor—was shown to increase the time to viral rebound, enhance immune function, and decrease levels of intact HIV DNA. Vesatolimod is being researched as part of a potential functional cure. Phase I and preclinical studies indicated the two drugs can activate the immune system, according to results presented by Gilead Sciences in 2019 at the 10th International AIDS Society Conference on HIV Science. The Phase I study, involving 48 people living with HIV and on antiretroviral treatment, found Vesatolimod was well-tolerated in addition to activating the immune system. A preclinical study of GS-986, using macaques, had similar results. These studies build on earlier research that demonstrated the potential of TLR7 agonists, used in combination with other drugs, to reduce or eliminate the reservoir.

ISLATRAVIR: Merck’s MK-8591 is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI). In Phase IIb trials of treatment-naive adults receiving ISL as part of a combination antiretroviral regimen, it was shown to have less of a (negative) impact on bone mineral density, making it a potential replacement for those with poor bone health. The drug uses a variety of methods to block the HIV enzyme known as reverse transcriptase, and researchers say it may be effective against HIV strains that are resistant to other drugs. A Phase Ib trial, results of which were published in The Lancet early this year, found a single oral dose of islatravir in treatment-naive patients significantly suppressed HIV; the drug was also well-tolerated. Researchers recommended “further development of islatravir as a flexible-dose treatment,” they noted in the article. A Phase IIb study will evaluate the effectiveness of three different doses of islatravir in combination with doravirine and lamivudine at first, then with doravirine only. It’s also being studied for HIV prevention, both as an oral med and as an implant. An implant study, results of which were presented in 2019, showed the implant had concentrations of the drug suitable to prevent infection for a year.

SHUTTERSTOCK

COMBINECTIN (GSK3732394): This is a long-acting HIV inhibitor being developed by Viiv Healthcare, using three modes of HIV entry inhibition. It was shown to be highly effective in a study of humanized mice. A proof-of-concept study in HIV-positive, treatment-naive humans was completed in February, but results have not been released.

The drug was taken orally in the study, but there is a possibility of using it as a subcutaneous injection.

GSK3640254: This is a maturation inhibitor, it prevents HIV from maturing. It does so by blocking a key step in the processing of gag, a protein that assembles HIV. A proof-of-concept study will evaluate its effectiveness, safety, and tolerability in treatmentnaive people with HIV. The drug comes from Viiv Healthcare.

ABX464: This drug being developed by Abivax is a Rev inhibitor, which interferes with the protein of that name to prevent HIV from multiplying.

Researchers believe it may reduce or eliminate the HIV reservoir that remains even after the virus is suppressed. A study in humanized mice showed long-term control of the virus even after treatment ended, and a human study showed reduction of viral reservoirs in blood and rectal tissue in virally suppressed patients.

ELPIDA (ELSULFAVIRINE, VM1500A): This is an NNRTI by maker Viriom. It was approved in Russia in 2017 as a once-daily oral HIV drug. Clinical studies are continuing into its use for dosing daily or weekly and have so far shown effectiveness, safety, and tolerability. Researchers are also looking at its use as part of a combination treatment and for HIV prevention, including as an injectable.

GS-9131: From Gilead Sciences, this is an NRTI for patients with resistance to other drugs in the class.

A study of its use in cell cultures, released in 2019, showed little resistance emerging. Dosing is being studied in Ugandan women, and Gilead has plans to coformulate it with other drugs from the company.

How Do Injectables Work?

THIS LONG-ACTING HIV TREATMENT IS THE WAVE OF THE FUTURE, EVEN FOR THOSE WHO HATE NEEDLES.

With injection meds, do folks usually inject themselves or does their doctor do it?

It depends on the specific medication and the patient’s comfort level. Some injectable medications need to be administered by a medical provider, especially long-acting medications, which are given once a month or less frequently. They must be injected in a specific area and specific way to make sure they release properly.

If done incorrectly, it could harm the patient. Medications, such as hormones and insulin, that are injected more frequently (daily or weekly) are more likely to be injected by the patient. I imagine many of the injectable HIV prevention and treatment medications will require administration by a medical professional. (Editor’s note: In Canada, the HIV drug Cabenuva is being administered via once-monthly injections in doctor’s offices.)

Do people have the option of going to a doctor’s office to have it done?

Yes. Regardless of the medication, some patients don’t feel comfortable injecting themselves. So, even if medications can be self-administered, they may come to the provider’s office to have it administered by nursing staff. These visits are likely to be billed to the patient’s insurance, which may be a factor in their decision to self-inject or not.

If you self-inject, do you need to buy needles or are they provided at a pharmacy?

Some medications may include the supplies needed to self-inject, but most require separate needles and syringes. Depending on state law, a patient may be able to purchase these at the pharmacy without a prescription, or the pharmacy may be able to bill them to insurance if the medical provider writes the supplies as a prescription. It generally depends on the patient’s prescription coverage.

Do they cost anything?

If they’re not included with the medication from the manufacturer or not covered by insurance, there is a cost— which varies due to size, quantity, and any special safety features of the needles and syringes.

Is there anything people should have handy when they selfadminister?

Patients should have alcohol prep pads to clean the area before injection and a sharps container to dispose the needle safely.

They should also be aware of where to return the sharps container when it’s full.* Also, a patient should undergo injection lessons for their specific medication from a doctor, nurse, or pharmacist prior to self-injecting. Different medications require different locations and techniques.— NE A L B R OV E R M A N *Editor’s note: Sharps containers are usually available at pharmacies, hospitals, retailers like Target and Walmart, and even online. If you can’t afford to purchase one and your FSA or insurance won’t cover it, a heavy duty laundry detergent container with puncture proof lid is also acceptable. Label it hazardous waste and check SafeNeedleDisposal.org for where or how to dispose of it when full.

SHUTTERSTOCK

This year, Canada became the first nation in the world to approve a monthly injectable all-in-one HIV treatment, ViiV Healthcare’s Cabenuva (a combination of the drugs cabotegravir and rilpivirine). While approval in the U.S. hit a bump over scale-up readiness, other injectable HIV treatments are on their way. Trogarzo, an injectable already approved for people with treatment resistant HIV, must be combined with other meds.

Other long-acting, all-in-one injectables are also in the pipeline.

Meanwhile, GlaxoSmithKline is finding success in an injectable HIV prevention treatment that is still in clinical trials. But exactly how does it all work? Nicole Thibeau, PharmD, director of pharmacy services at the Los Angeles LGBT Center, answers our burning questions.

WHEN SHOULD YOU TALK TO YOUR DOCTOR ABOUT CHANGING THE HIV DRUGS YOU’RE TAKING?

SHUTTERSTOCK

BY JACOB ANDERSON-MINSHALL

It is now well documented that it is safe, and sometimes highly advantageous, to switch from one HIV treatment to another. If you are already undetectable, you can switch without risking your viral suppression. If you are struggling to take your meds as prescribed, facing daunting side effects, dealing with a comorbidity (like high cholesterol or liver disease), experiencing certain health concerns (say fragility as you age), or have changing lifestyle issues (unusual work hours) then talking to your doctor about reevaluating your medications can be the right choice.

It can be confusing, because studies aren’t always conclusive, combination drugs can come with different recommendations than their individual elements, and if you have more than one health concern (like most of us) your doctor may need to recommend which has priority in choosing your HIV medication. Share our Annual Treatment Guide at your next appointment and discuss whether a simple switch could change your life. If the therapy you choose doesn’t turn out to be ideal, you can always switch again.

2

IF YOU WANT TO REDUCE THE NUMBER OF DRUGS YOU TAKE. Although three-drug regimens were once considered essential in preventing the development of HIV drug resistance, new two-drug regimens have proven to be just as effective.

Their advantages include fewer side effects, and a reduction in toxicity associated with long-term drug therapies. Juluca (dolutegravir/rilpivirine) was the first twodrug regimen approved by the FDA. This year the DUALIS study demonstrated that dolutegravir and boosted darunavir are as effective as a three med regimen.

3

IF YOU TAKE YOUR MEDS WITHOUT FOOD. A lot of HIV drugs not only must be taken with food but must be taken with a specific type of food (protein or a hearty meal, rather than a snack). So if you’re the kind of person who either doesn’t eat that way or forgets your meds until later, you should consider a drug that has no food intake requirements, such as Biktarvy (bictegravir/ emtricitabine/tenofovir alafenamide) or Truvada (emtricitabine/tenofovir disoproxil fumarate).

4

IF YOU NEED TO BE MORE HEART HEALTHY. Some drugs, like Triumeq, come with certain cardiovascular risks, so those with higher risks of heart disease should instead consider tenofovir-based medications, such as Stribild (elvitegravir/ cobicistat/emtricitabine/tenofovir disoproxil fumarate) or Genvoya (elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide).

5 6 7 8 9 10

IF YOU ALSO HAVE HEPATITIS C. According to the Centers for Disease Control and Prevention, approximately 25 percent of people with HIV in the United States also have hepatitis C. There are new, curative hep C treatments available, but many HCV drugs interact with HIV drugs, so it’s important for your doctor to carefully consider which medications you can take while treating them simultaneously.

IF YOU ARE PREGNANT “When a woman living with HIV is expecting, she can be confident that the same antiretroviral therapy she takes every day to protect her own health also helps protects her future child from acquiring HIV,” NIAID director Anthony S. Fauci reiterated at this year’s CROI, adding, “Findings from the VESTED study suggest that a drug regimen containing dolutegravir provides the safest, most effective HIV treatment available during this critical time for women and their infants.”

IF YOU HAVE KIDNEY OR LIVER PROBLEMS. Tenofovir disoproxil fumarate (TDF, brand name Viread, and a component in the single-tablet regimens Truvada, Atripla, Complera, and Stribild) has been linked to kidney problems in susceptible individuals, so those with kidney issues might consider regimens that instead use tenofovir alafenamide (TAF), such as Genvoya, Odefsey, and Descovy. Juluca, which overall promises fewer side effects, has seen some users develop worse or new liver problems.

IF YOU CAN’T DEAL WITH THE SIDE EFFECTS. Every medication has potential side effects—some minor, some life-threatening. Not everyone taking the medication will experience the same side effects, and some people experience them more intensely. Only you can decide if the side effects aren’t worth the benefits you’re getting from a particular medication.

With so many treatment options now available, don’t hesitate to talk to your doctor if you feel side effects are impacting your daily life.

IF YOU ARE AFRICAN-AMERICAN. A sad truth is that few drug trials test the impact of a treatment on people of color, especially women. That’s what makes this year’s BRAAVE study so remarkable. It involved 495 self-identified Black or African-American poz folks (32 percent were cisgender women) who switched to Biktarvy from a variety of regimens. While 96.3 percent of those who switched maintained viral suppression, fewer (94.5 percent) of those who stayed on their original regimen did.

IF YOU ARE CONCERNED ABOUT GAINING WEIGHT. At the 2020 Conference on Retroviruses and Opportunistic Infections, researchers shared more data confirming that some HIV drugs lead to weight gain. Taking integrase inhibitors (dolutegravir or raltegravir) was previously associated with greater weight gain than taking nucleoside reverse transcriptase inhibitors. Now more of those taking TAF/FTC+DTG were shown to develop clinical obesity compared to TDF/FTC+DTG or TDF/FTC/EFV. Weight gain isn’t just bad because of those love handles; it also raises your risks of diabetes and heart disease.

SHUTTERSTOCK

1

IF YOU ARE WORRIED ABOUT DRUG-RESISTANCE. Some drugs offer more protection against HIV developing resistance. For example, the ODIN trial found that darunavir (a component of both Prezista and Prezcobix) stops the virus from multiplying and mutating. (Symtuza also offers a high barrier to resistance, but isn’t for those already on treatment.) Just because you’ve developed a resistance to one drug, or one or more classes of drugs, doesn’t mean that other HIV meds won’t work for you. For example, Trogarzo (ibalizumab) a longacting injectable, fights multidrug-resistant HIV when added to a previously failing antiretroviral regimen.

INTEGRASE STRAND TRANSFER INHIBITORS (INSTIs) Drugs in this class block integrase, an enzyme HIV needs in order to reproduce. HIV uses integrase to insert its viral DNA into the DNA of T cells. Blocking the integration process prevents HIV from replicating. They are always taken with other HIV medication.

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs, also known as nukes) Drugs in this class block reverse transcriptase, an enzyme that HIV needs in order to reproduce.

HIV uses reverse transcriptase to convert its RNA into DNA, blocking the reverse transcription process prevents HIV from replicating. They are always taken with at least one other HIV med.

NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs, also known as nonnukes)

CLASS WARFARE HIV DRUG CLASSES FIGHT THE VIRUS THROUGH DIFFERENT MODES OF ATTACK.

Drugs that treat HIV, known broadly as antiretroviral medications, are grouped in various classes based on methods the drug uses to attack the virus. HIV treatment regimens include drugs from multiple classes to improve their combined effectiveness and help prevent the development of drug resistance. Here are brief descriptions of the classes and how they work.

BROADLY NEUTRALIZING ANTIBODIES (bNAbs) Drugs in this class are antibodies that can recognize and block HIV or activate other immune cells to help destroy the virus. Some hold potential to treat HIV without other medications.

CCR5 ANTAGONISTS (CAs) Drugs in this class block the CCR5 coreceptor on the surface of CD4 cells preventing HIV from binding and entering the cells.

CAPSID INHIBITORS (CIs)

SHUTTERSTOCK

Drugs in this class help inhibit the proteins that protect HIV’s genetic material, help the virus’ genetic material enter the cell nucleus, and help the new copies of HIV become infectious. They are still in trails, but may not need to be taken with other HIV medication.

ENTRY AND FUSION INHIBITORS (EIs and FIs) Drugs in this class help block HIV from binding, fusing, and entering T cells. They are always taken with other HIV medication.

Drugs in this class also block reverse transcriptase, as NRTIs do, but in a different way.

They are always taken with at least one other HIV medication.

NUCLEOSIDE REVERSE TRANSCRIPTASE TRANSLOCATION INHIBITORS (NRTTIs) Drugs in this class also block reverse transcriptase but do so by preventing translocation of an enzyme They are always taken with other HIV medication.

PHARMACOKINETIC ENHANCER/CYP3A INHIBITORS (PKEs, also known as boosters) Drugs in this class boost the effectiveness of antiretroviral medication. When the two are taken together, the pharmacokinetic enhancer slows the breakdown of the other drug, which allows the drug to remain in the body longer at a higher concentration. They are always taken with other HIV medication.

POST-ATTACHMENT INHIBITORS (PAIs) Drugs in this class bind to CD4 cells after HIV has attached to them, but still inhibit the HIV virus from successfully infecting those cells. They are always taken with other HIV medications.

PROTEASE INHIBITORS (PIs) Drugs in this class block activation of protease, an enzyme HIV needs to develop. Blocking protease prevents immature forms of HIV from becoming a mature virus capable of infecting other T cells.

They are always taken with other HIV medication.

SINGLE-TABLET REGIMENS (STRs) Drugs in this category are fixed-dose pills that combine multiple anti-HIV medications (often from more than one class of drug) into a single tablet, which is usually taken just once a day.

They do not need to be taken with other HIV medication.

TOLL LIKE RECEPTORS (TLR) Drugs in this class, stimulate the immune system’s T cells, activating a more robust response to the viral invader. They are always taken with other HIV medications.

STAY CONNECTED, STAY HEALTHY Today, there are more ways than ever to stay connected to care and get (or keep getting) your meds while sheltering in place and practicing social distancing. Still, for many of us, the disruption to our regular routine has proven to be, at times, stressful, depressing, and confusing.

Perhaps pre-pandemic you preferred picking up your meds at a local clinic where you could also chat with a trusted healthcare provider. Or maybe the local pharmacy you normally use doesn’t offer online prescription refilling or free med delivery. With literally hundreds of online prescription services to choose from, the task of choosing one can be a bit overwhelming. Who can you trust?

SHUTTERSTOCK

SOCIAL DISTANCING MAY HAVE PROVIDED ADDITIONAL BARRIERS FOR MANY LIVING WITH HIV, BUT THERE ARE LOTS OF ONLINE OPTIONS TO KEEP YOU CONNECTED TO CARE AND YOUR MEDS.

The good news is that these days most pharmacies (even local mom and pop shops) do provide online prescription ordering and refills as well as home delivery, so check first with the pharmacy you’ve been using to see what options they offer. Your healthcare provider or HMO may also have a mail-order delivery that sends you 90 days of meds at a time (Kaiser Permanente is one that does).

If you do have to find a new way to obtain your meds, be sure to find a pharmacy that has a specific program for people living with HIV. Partnered with the Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services, CVS Health offers a few HIV-related programs including Ready, Set, PrEP (for those hoping to prevent transmission) and its Specialty HIV Care Management program (for those living with HIV already). Using a holistic approach, patients receive one-on-one support from nurses specially trained in HIV care whom they can easily reach by phone anytime. The program also offers online med ordering and refills, free delivery, and cost-management assistance—often helping you get your HIV meds free or at a very low cost.

“CVS Health is dedicated to improving the lives of those at-risk and those living with HIV and other chronic conditions,” said Kevin Hourican, executive Vice President of CVS Health and president of CVS Pharmacy, when it announced its Ready, Set, PrEP program last fall. CVS was one of the first pharmacies to donate medication dispensing services of PrEP at no cost to individuals.

Walgreens, which has also partnered with the CDC as well as Greater Than AIDS (GreaterThan.org), has its own HIVspecialized pharmacies that offer testing, financial assistance, and over 1,000 specially trained pharmacists on-call. Free prescription delivery is available in most areas.

If you live in a more remote area where major pharmacies can’t deliver, a good bet would be the AIDS Healthcare Foundation.

Though it’s Los Angeles-based, AHF provides in-person and virtual care and prescription services (AHFpharmacy.org) across the United States. Automatically refill meds

whenever you need them through its app and speak to a live person via its 24/7 customer care line (1-855-894-6337). If unable to serve you directly, they will quickly connect you to local providers that can. AHF also offers financial assistance programs.

In addition to these major national treatment providers, there are also numerous specialty pharmacies and orgs throughout the U.S. that focus specifically on HIV treatment and prevention, making them a good option for those who are newly diagnosed—or who just want more personalized care. Two examples are Avella Specialty Pharmacy (Avella.com) and BioMatrix Specialty Pharmacy (BioMatrixsPRX.com), which both mainly work virtually and supply meds nationwide.

Both also offer specialized HIV care programs, virtual doctor’s appointments and med ordering, fast delivery, and financial assistance programs.

Two more localized examples are Avanti Health Care (AvantiHealth.com) and Avita Pharmacy (AvitaPharmacy.com). Avanti was founded in 1993 as a single retail pharmacy in Manhattan and now provides multiple specialized services, such as medication therapy management, medication adherence programs, and hospice pharmacy services.

Though Avanti primarily serves the greater NYC area (where you can often get sameday delivery), it’s also licensed to ship meds throughout the states of New York, New Jersey, and Florida on a per-case basis. Avita is an HIV specialist pharmacy that can work with clients in nine Southern states (including Texas, Louisiana, and Mississippi) as well as Oregon. It is highly likely that your region has similar orgs that can help you.

When searching online for treatment providers that deliver to your area, some handy search terms to use are “HIV specialized pharmacies,” “HIV pharmacies,” or “HIV Service Providers,” followed by “near me.” You can also visit the American Academy of HIV Medicine’s website (AAHIVM.org) to search its huge referral database of HIV organizations and specialty pharmacies across the U.S. —DE S IRÉ E G U E RRE RO