COTTONBRO/PEXELS GUIDETREATMENTHIVANNUAL10OURTH
BY PLUS EDITORS
Our breakdown of the most commonly-prescribed, FDA-approved medications for the treatment (and prevention) of HIV and its related conditions.
generic name: cabotegravir and rilpivirine class of drug: single-injection regimen maker: ViiV Healthcare who is it for? Those 12 and older
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Cimduo
generic name: dolutegravir and lamivudine 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).
Cabenuva
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
Edurant
traditional dosage: One 25 mg tablet once daily with meal. It is always taken with
otherwise noted, all dosages are the traditional adult dose.
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).
Biktarvy
traditional dosage: One tablet once daily. Adult tablet includes 50 mg of bictegravir (an INSTI), 200 mg of emtricitabine (Emtriva, an NRTI), and 25 mg of tenofovir alafenamide (an NRTI). This year, the FDA approved a new low-dose tablet (30 mg bictegravir/120 mg emtricitabine/15 mg tenofovir alafenamide) for pediatric patients weighing at least 14 kg to less than 25 kg who are virologically suppressed or new to antiretroviral therapy. Does not need to be taken with other HIV drugs.
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. for hiv treatment: One tablet per day in combination with other antiretrovirals. Each tablet contains 200 mg emtricitabine (Emtriva) and 25 mg tenofovir alafenamide (TAF). A lower-dose option (120 mg Emtriva, 15 mg TAF) is also now available. for hiv prevention: One tablet once daily. Must be paired with regular HIV tests and safer sex practices. Descovy for PrEP is not currently FDA-approved for individuals assigned female at birth.
weighing at least 35 kg who have no history of treatment failure and no known or suspected resistance to either cabotegravir or rilpivirine.
impairment or severe liver impairment. traditional dosage: One tablet once daily. Tablet contains 100 mg doravirine (Pifeltro, an NNRTI), 300 mg lamivudine (Epivir, an NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, an NRTI).
generic name: emtricitabine, rilpivirine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Gilead Sciences who is it 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, an NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, an NRTI).
traditional dosage: Monthly injection of 400 mg of cabotegravir and 600 mg of rilpivirine, after an initial injection of 600 mg of cabotegravir and 900 mg of rilpivirine. As of this year, an oral lead-in period of one month prior to your first injection is no longer required.
traditional dosage: One tablet once daily. Tablet contains 600 mg efavirenz (Sustiva, an NNRTI), 200 mg emtricitabine (Emtriva, an NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, an NRTI).
generic name: bictegravir, emtricitabine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For those 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, hepatitis B, or severe liver impairment.
Atripla
generic name: rilpivirine class of drug: nonnucleoside 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.
Unless
generic name: efavirenz, emtricitabine, and tenofovir disoproxil fumarate class of drug: single-tablet regimen maker: Gilead Sciences who is it for? For those 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.
Complera
Delstrigo
Dovato
Descovy
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
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. A 10-mg/mL oral solution is also available for children or others who have difficulty swallowing tablets (daily dosage based on patient’s weight).
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.
generic name: dolutegravir and 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, an NRTI).
Epivir
Epzicom
Isentress generic name: raltegravir class of drug: integrase inhibitor maker: Merck
traditional dosage: One tablet once daily. Tablet contains 150 mg of elvitegravir (an INSTI), 150 mg cobicistat (Tybost, a PKE), 200 mg emtricitabine (Emtriva, an NRTI), and 10 mg tenofovir alafenamide (an NRTI).
other antiretrovirals. Is also a component in single-tablet regimens Complera, Odefsey, and Juluca.
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. There is also a 10-mg/ mL oral solution available (daily dosage is adjusted depending on patient’s current creatinine levels).
generic name: elvitegravir, cobicistat, 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 25 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 drug resistance to the components of Genvoya. Not recommended for those who have a creatinine clearance below 30 mL per minute.
generic name: etravirine class of drug: nonnucleoside 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.
Emtriva
who is it for? For those new to 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.
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: 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 virologicallysuppressed for at least six months.
traditional dosage: One tablet once daily. Tablet contains 200 mg of emtricitabine (Emtriva, an NRTI), 25 mg of rilpivirine (Edurant, an NNRTI), and 25 mg of tenofovir alafenamide (an NRTI).
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Genvoya
Intelence
Juluca
Norvir
Odefsey
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.
Pifeltro
Rukobia
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.
generic name: doravirine class of drug: nonnucleoside reverse transcriptase inhibitor maker: Merck who is it for? For adults as part of an initial regimen.
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
Selzentry
generic name: darunavir, cobicistat, emtricitabine, and tenofovir alafenamide class of drug: single-tablet regimen maker: Janssen who is it for? For treatment-naive or those with a suppressed viral load on a stable HIV regimen for at least six months
generic name: fostemsavir class of drug: attachment inhibitor maker: ViiV Healthcare who is it for? Adults who have received several antiretroviral regimens in the past, who have virus that is resistant to many antiretroviral drugs, and whose current antiretroviral therapy is either ineffective, causing side effects the patient cannot tolerate, or causing other safety concerns.
traditional dosage: One tablet once daily. Tablet contains 150 mg of elvitegravir (an INSTI), 150 mg cobicistat (Tybost, a PKE), 200 mg emtricitabine (Emtriva, an NRTI), and 300 mg tenofovir disoproxil fumarate (Viread, an NRTI).
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 use during pregnancy and for those with a creatinine clearance below 70 mL per minute, severe liver problems, or hepatitis B.
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traditional dosage: One tablet, 100 mg, once daily, taken in combination with other antiretrovirals.
Symtuza
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).
Stribild
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.
Sustiva
Prezista
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.
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).
Reyataz
Symfi/Symfi Lo
traditional dosage: One tablet, once daily, on an empty stomach. Symfi contains 600 mg efavirenz (Sustiva, an NNRTI), 300 mg lamivudine (Epivir, an NRTI) and and 300 mg tenofovir disoproxil fumarate (Viread, an NRTI). Symfi Lo contains 400 mg efavirenz, 300 mg lamivudine, and 300 mg TDF.
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. 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.
traditional dosage: One 600mg tablet, twice daily, around the same time each day, with or without food, and in combination with other antiretroviral drugs.
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.
Prezcobix
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.
Tybost
traditional dosage: One 300 mg tablet once daily.
Vocabria
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.
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.
abacavir sulfate (Ziagen, an NRTI), 50 mg dolutegravir (Tivicay, an INSTI), and 300 mg lamivudine (Epivir, an NRTI).
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Trogarzo 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.
Viread
traditional dosage: One 300 mg twice daily or two 300 mg once daily. Individuals with mild liver impairment should take 200 mg twice daily.
generic name: cabotegravir class of drug: integrase strand transfer inhibitor maker: ViiV Healthcare who is it for? Adults who have achieved viral suppression on a stable regimen and have no history of treatment failure and no known or suspected resistance to cabotegravir. To be used either as a month-long lead-in to monthly injections of Cabenuva (cabotegravir and rilpivirine) or by patients who will miss an injection.
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. Tablet contains 600 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 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, an NRTI), and 10 mg TAF (an NRTI).
Truvada
generic name: tenofovir disoproxil fumarate class of drug: nucleoside reverse 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 30mg tablet with one 25mg rilpivirine tablet, once daily, with a meal.
Temixys
Tivicay
generic name: cobicistat class of drug: pharmacokinetic enhancer/CYP3A inhibitor/ booster maker: Gilead Sciences 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.
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.
traditional dosage: One 150 mg tablet daily with food, with either 300 mg atazanavir or 800 mg darunavir.
Ziagen
with no known resistance to darunavir or TAF. Not for those with severe liver or kidney impairment.
traditional dosage: One tablet once daily. Contains 300 mg lamivudine (Epivir) and 300 mg TDF.
generic name: emtricitabine and 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 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 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.
traditional dosage: A loading dose of 2,000 mg, administered as an injection, followed by a maintenance dose of 800 mg every two weeks.
Triumeq
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. Vesatolimod is being researched as part of a potential functional cure. At CROI 2020, Gilead
LENCAPAVIR (GS-6207): Developed by Gilead Sciences, this first-inclass 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 the 2021 Conference on Retroviruses and Opportunistic Infections, researchers reported that lenacapavir administered subcutaneously every six months helped patients maintain high rates of viral suppression through 26 weeks. 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. An issue with how the drug was stored prompted the FDA to place a clinical hold on lenacapavir’s Investigational Drug Application late last year, but Gilead announced in May the issue was resolved and the hold was lifted, allowing screening and studies to continue.
IN PIPELINETHE
VYROLOGIX (LERONLIMAB- PRO 140): CytoDyn’s viral-entry inhibitor is a monoclonal antibody that would be the first self-injectable subcutaneous HIV drug. It works by masking CCR5, a protein on the surface of white blood cells, thus inhibiting HIV’s ability to enter healthy T cells. There have been at least nine clinical trials indicating it could significantly reduce or control viral load. For instance, a Phase III trial involving treatmentexperienced 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). The drug was also being studied as treatment for COVID-19, metastatic cancer, stroke, and a chronic liver disease called nonalcoholic steatohepatitis, but that was complicated in March after the FDA placed a partial clinical hold on its HIV program and a full clinical hold on its COVID-19 program in the United States. “CytoDyn is committed to FDA compliance,” Scott A. Kelly, M.D., Chief Medical Officer of CytoDyn, said in a statement. “We are evaluating our clinical programs and are working to resolve the issues underlying the clinical holds as soon as possible in close communication with the FDA. We will provide an update when we have additional information.”
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Brush up on the status of several HIV drugs in development, which could offer new treatments, preventions, and even a cure.
BY TRUDY RING AND NEAL BROVERMAN
PGT 121: 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 Sciences, 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. Then a study published in 2021 reported that PGT121, in combination with other drugs, delayed rebound of simian HIV in monkeys whose antiretroviral treatment had been interrupted. PGT121 could eventually become a very long-acting HIV medication or a functional cure that maintains viral suppression after antiretroviral therapy has ended. A study published early this year showed subcutaneous injections of PGT121 paired with another broadly neutralizing antibody, VRC07-523LS, served as effective protection against HIV among a group of young South African women.
UB-421: In a Phase II trial, this broadly neutralizing antibody targeted domain 1 of CD4, and 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 e ffi cacy in patients with multidrug-resistant HIV.
LEFITOLIMOD (MGN1703): Lefitolimod is a type of latency-reversing 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 2019 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.
HIV was identified over 40 years ago and medical and scientific advances against the disease continue to roll out on a regular basis. Since AZT was approved in 1987, HIV medications have grown leaps and bounds, alleviating side effects, reducing required dosages, and, most recently, introducing injectable options that end the need for daily pills. Scientists in the HIV field are currently working to utilize lessons learned from COVID-19 in hopes of battling drug resistance and eliminating reservoirs of HIV that still exist in the cells of people on antiretroviral regimens and whose viral loads remain undetectable. Here are some of the HIV drugs that have the most potential for approval by the Food and Drug Administration and could soon be coming to a pharmacy near you.
ALBUVIRTIDE AND 3BNC 117: Albuvirtide is a fusion inhibitor, meaning it keeps HIV from entering certain cells in the immune system. From Frontier Biotechnologies, it is already approved for use in China. In the U.S., it is being studied in combination with 3BNC117, a broadly neutralizing antibody developed by Rockefeller University, for treatment of patients whose antiretroviral regimen is failing. Broadly neutralizing antibodies can block HIV from entering healthy cells and activate other immune cells to help destroy infected cells. Scientists are also looking into the possibility of using 3BNC117 in HIV prevention. Additionally, Frontier announced in July 2021 a successful study of albuvirtide paired with the antiretroviral drug lopinavir, reporting the two-drug combination was nearly as effective as a lopinavir-based threedrug treatment.
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.
GSK3640254: This is a maturation inhibitor from ViiV Healthcare; it prevents HIV from reaching its end stage. It does so by blocking a key step in the processing of gag, a protein that assembles HIV. Results of a proof-of-concept study, presented at CROI 2021, showed that the drug was safe and welltolerated, and helped suppress HIV in treatmentnaive adults. Participants in the study received various doses of GSK3640254 or a placebo over several days; the 140mg and 200mg doses were most effective against the virus. Now GSK3640254 is being studied as part of combination therapy in treatment-naive people; such maturation inhibitors also may offer a new option to people for whom other treatments haven’t worked. A study’s findings,
MK-8504 AND MK-8583: These NRTIs being developed by Merck are new prodrugs of tenofovir, itself a component of many HIV treatments; a prodrug is a substance that has to be broken down by the body to become active. MK-8504 and MK-8583 were developed with an eye to them being weekly treatments due to the long half-life of the drugs, but Phase I studies presented at CROI in 2020 showed weekly doses had only modest and transient activity against HIV. Daily doses may produce a better result, researchers said.
Sciences’ 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. Later that year, at the International AIDS Conference, one study that was presented indicated that injectable vesatolimod, used with other antiretroviral drugs, helped speed up HIV suppression in monkeys. Another study presented at the latter conference looked at humans who are HIV controllers — those in whom HIV doesn’t replicate for an extended period even if they aren’t on antiretroviral treatment, but who may need to go on treatment eventually. That study found that in controllers who had finally begun treatment, the addition of oral vesatolimod enhanced the immune system’s response, a promising if early result. A recent study in Spain looked at combining the drug with therapeutic vaccines — vaccines that are given not to prevent an infection but to control one.
SHUTTERSTOCK
released early this year, showed GSK3640254 to be safe, effective, and welltolerated among people living with HIV with little or no exposure to treatment.
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 e ff ectiveness, safety, and tolerability. Researchers are also looking at its use as part of a combination treatment and for HIV prevention, including as an injectable.
BY JACOB ANDERSON - MINSHALL AND DESIRÉE GUERRERO
If you are already undetectable, you can switch without risking your viral suppression. Tell your prescribing doctor the concerns you have and let them help ne-tune your treatment so it ts your speci c needs.
36 JULY / AUGUST 2022 COTTONBRO/PEXELS
10 reasons to change HIV medications now.
Read on for our tips to know when it may be a good time to discuss switching with your doc (and don’t forgot to bring our annual Treatment Guide with you!):
TIME SWITCHTO GEARS
If your HIV medication is working well for you without any signi cant side effects or issues, there may be no need to consider switching up your regimen. However, it is safe — and sometimes highly advantageous — to switch from one HIV treatment to another. With more options than ever before, it can be challenging to choose which regimen might be right for you — which is why it’s important to discuss it with your doctor rst.
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 some 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.
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YOU ARE CONCERNED ABOUT GAINING WEIGHT. At CROI 2021, 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. Recent studies indicate, however, that tenofovir alafenamide, an NRTI, is linked to weight gain. Weight gain can also raise your risks of diabetes and heart disease, so if these are concerns of yours, remember to discuss them with your doctor.
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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 2020’s BRAAVE study so remarkable. It involved 495 selfidentified Black or African-American HIV-positive people (32 percent were cisgender women) who switched to Biktarvy from a variety of regimens. Virtually all of those who switched maintained viral suppression.
IF YOU ARE WORRIED ABOUT DRUG RESISTANCE. Some drugs offer more protection against resistance developing. Darunavir (a component of both Prezista and Prezcobix) stops the virus from mutating, and thus developing resistance. A threeyear study of those taking (bictegravir/emtricitabine/tenofovirBiktarvyalafenamide)foundnodrugresistance.Ifyoudodevelopadrugresistance,otherHIVmedscanstillworkforyou.Forexample,Trogarzo(ibalizumab),along-actinginjectable,fightsmultidrug-resistantHIVwhenaddedtoapreviouslyfailingantiretroviralregimen.
YOU HAVE KIDNEY OR LIVER PROBLEMS. Tenofovir disoproxil fumarate (TDF, brand name Viread, and a component of drugs including Atripla, Complera, Delstrigo, 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 Biktarvy, Genvoya, Odefsey, or Descovy. Overall, Juluca has fewer side effects, but has seen some users develop new or worse liver problems.
5IF
2IF
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 (with protein or a hearty meal, rather than just a snack). If you don’t eat big meals or prefer to take your meds at bedtime instead, or you often forget to take your meds when you go out to lunch with work friends, you should consider a drug that has no food intake requirements, such as Biktarvy (bictegravir/ emtricitabine/tenofovir alafenamide) or Triumeq (dolutegravir/abacavir/lamivudine).
6IF
HIVPLUSMAG.COM 37
Pregnancy and Prevention of Perinatal Transmission recommend dolutegravir-based regimens for pregnant people, irrespective of trimester, and for people who are trying to conceive. Based on additional data, the panel now also recommends tenofovir alafenamide as a preferred NRTI for antiretroviral regimens in people who are pregnant or trying to conceive.
8
9IF
IF YOU CAN’T DEAL WITH THE SIDE EFFECTS. Every medication has potential side effects — some minor, some life-threatening. Not everyone taking a certain 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 negatively affecting your daily life.
YOU WANT TO STOP TAKING PILLS ALL TOGETHER. Last year the FDA approved Cabenuva (rilpivirine and cabotegravir), making it the first complete antiretroviral regimen that comes in an injection. Doses are administered every two months at your doctor’s office.
YOU ARE PREGNANT. Some HIV medications may increase risks of birth defects and the effect of others, like cabotegravir, on fetuses haven’t been well studied. In updated guidelines, the Department of Health and Human Services’ Panel on Treatment of HIV During
10IF
YOU WANT TO REDUCE THE NUMBER OF MEDS YOU TAKE. Although three-drug regimens were once considered essential in preventing drug resistance, twodrug 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), Dovato (dolutegravir/lamivudine) and Cabenuva (rilpivirine/cabotegravir) are all two-drug regimens now approved by the Food and Drug Administration.
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38 JULY / AUGUST 2022
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 (TRANSCRIPTASEREVERSEINHIBITORSNRTIS,ALSOKNOWNASNUKES):
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.
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS, ALSO KNOWN AS NONNUKES): 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.
BY PLUS EDITORS
HIV treatment regimens include drugs from multiple classes to improve their combined effectiveness, decrease toxicity, and help prevent the development of drug resistance. Here’s brief descriptions of these classes and how they work.
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 process prevents HIV from replicating. They are always taken with at least one other HIV med.
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.
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.
CAPSID INHIBITORS (CIS): These drugs are still in trials and not yet FDA-approved, but meds in this class help inhibit the proteins that protect HIV’s genetic material. CIs are currently being used as a component in experimental long-acting regimens such as injectables. They may not need to be taken with other HIV medications.
A major reason that HIV had been historically difficult to combat in terms of treatment is because it is a retrovirus. This means it contains single-stranded RNA (ribonucleic acid) instead of the typical doublestranded DNA that human cells carry. Retroviruses also carry an enzyme called “reverse transcriptase,” which allows it to copy RNA into DNA — and then use that DNA copy to invade human Fortunatelycells.
ACTSCLASS
NUCLEOSIDE INHIBITORSTRANSCRIPTASEREVERSETRANSLOCATION(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.
scientists developed antiretroviral drugs in the mid-1990s that were able to prevent HIV from replicating in the human body. This breakthrough was truly miraculous, in that it changed HIV from an often fatal disease to a manageable chronic condition much like diabetes. Since then, HIV drugs have only improved.
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 virus from 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.
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.
HIVPLUSMAG.COM 39
Each class of HIV drugs fights the virus in unique ways.
SINGLE TABLET REGIMENS (STRS): Drugs in this category are xeddose 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.
SHVETS/PEXELSANNA
Here’s what you need to know about the most common HIV medication side effects and comorbidities — and how to treat them.
BY DIANE ANDERSON MINSHALL
40 JULY / AUGUST 2022 SHUTTERSTOCK
Side Effect:HighHypertension/BloodPressure
how common: Extremely; in fact, diarrhea is among the most common reasons why people with HIV stop or switch their HIV meds.
HIVPLUSMAG.COM 41
how common: It’s the second leading cause of death among people living with HIV. treatment : It may include a variety of approaches. There are cholesterol-lowering statin drugs such as Crestor, Lipitor, Zocor, Vytorin, Lescol, Mevacor, Altoprev, Livalo, Pravachol, Advicor, and Simlup. Programs that help you stop smoking, shed excess pounds, and exercise more are all useful. Reduce alcohol and sodium consumption. If your blood pressure is not in a healthy range, your doctor may prescribe medication. Among the options are ACE inhibitors (Vasotec, Prinivil, Zestril, Altace); angiotensin II receptor blockers (Cozaar, Atacand, Diovan); beta blockers (Lopressor, Toprol XL, Corgard, Tenormin); or calcium channel blockers (Norvasc, Cardizem, Dilacor XR, Adalat CC, Procardia).
Comorbidity: Diabetes
treatment : Selective serotonin reuptake inhibitors (SSRIs) are most effective. According to the National Institutes of Health, medications that have shown efficacy in treating depression in patients with HIV include (generic names) imipramine, desipramine, nortriptyline, amitriptyline, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, nefazodone, trazodone, bupropion, and mirtazapine.
how common: There’s a type of diabetes caused by pancreatic damage brought on by HIV medications. It’s less common than the other two types, Type 1 and Type 2, but equally damaging. treatment : Controlling blood sugar, medication, insulin treatment, and proper diet are the main treatments, with regular doctor screenings for easy-to-miss complications. Diabetes meds include Lantus, Januvia, Humalog, NovoRapid, Victoza, Farxiga, and about a dozen more.
Side Effect: Mood Changes, Including Depression and Anxiety
how common : According to a 2019 study published in International Journal of Environmental Research and Public Health, 39 percent of people living with HIV were currently experiencing depression. AIDS Beacon previously reported that 63 percent of HIV-positive participants “reported symptoms of depression currently or at some point in the past. Overall, 26 percent of patients reported having had thoughts of suicide and 13 percent of participants reported having attempted suicide in their lifetimes.”
treatment: Stop smoking. Medications include vasodilators (hydralazine), antihypertensives (Cozaar, Avapro, Diovan), ACE inhibitors (Prinivil, Lotensin), calcium channel blockers (Norvasc, Procardia, Plendil), and diuretics (Microzide, Diuril, Zestoretic).
how common: Very. The U.S. Department of Veterans Affairs, for example, reports that 45 percent of its patients with HIV also have a hypertension diagnosis. A report from last year found that a quarter of all people with HIV also have hypertension, with the comorbidity most prevalent in North America and Western Europe. A 2018 review of findings, published in Hypertension, suggests that chronic inflammation associated with HIV and antiretroviral therapy is a major factor in the high rates of hypertension.
Side Effect: Injection Site Pain
treatment: Three options: over-the-counter anti-diarrheal medicines such as Imodium (loperamide); Lomotil (diphenoxylate and atropine), which slows the gut to combat diarrhea and is commonly given to cancer patients; or Mytesi (crofelemer), the only Food and Drug Administration-approved drug to relieve noninfectious diarrhea in HIV-positive people. Derived from the red sap of the Croton lechleri plant, Mytesi is only the second botanical prescription drug approved by the FDA.
how common: Osteopenia and osteoporosis are both forms of bone density loss, with the latter being more severe. Far more people with HIV have osteopenia (60 percent) versus osteoporosis (10-15 percent). The lower your body weight, the more susceptible you are to both. Fracture injuries are more common in young poz people because of it. treatment: Bisphosphonate therapy with vitamin D and calcium supplementation and medications including Fosamax, Boniva, Actonel, Atelvia, and Reclast. And just this year, a study presented at the virtual Conference on Retroviruses and Opportunistic Infections indicated that a “short course of alendronate” (the generic term for Fosamax and Binosto) at the beginning of tenofovir-based antiretroviral therapy can help prevent bone loss.
Comorbidity: Cardiovascular Disease
Side Effect: Diarrhea
how common: Very, with Cabenuva (cabotegravir and rilpivirine), the FDA-approved once-monthly or every-two-months injectable treatment for HIV-1 in virologically suppressed adults and adolescents aged 12 and older. According to the FDA, 61 percent of patients using cabotegravir and rilpivirine reported an adverse reaction. The most common of these were pain at the injection site and insomnia, but also included fever (pyrexia), fatigue, headache, musculoskeletal pain, nausea, dizziness, and rash. treatment: Discontinuation of cabotegravir and rilpivirine in the event of Grade 3 reactions such as drug hypersensitivity and severe insomnia.
Comorbidity: Osteoporosis and Osteopenia
There are now more HIV prevention methods available than ever — and it’s putting the joy back into sex for people living with HIV.
42 JULY / AUGUST 2022
BY DESIRÉE GUERRERO
SUBIYANTO/PEXELSKETUT
Also always check with your doc about the possible side effects and drug interactions of each type, to make sure you choose the safest option for you. The most common side effects of PrEP include headaches, fever, chills, and other flu-like systems — but for most they lessen and disappear over time.
PrEP is recommended for people considered “at-risk” of contracting HIV. This includes people who’ve consistently had unprotected anal or vaginal sex in the last six months, IV drug users, and those with an HIV-positive partner who want to become pregnant. There may be other reasons one might fall into the high-risk category, so you should talk to your health care provider if you think PrEP might be for you.
Today, there are three FDA-approved forms of PrEP available in the United States: Truvada, Descovy, and Apretude, with the latter being a new one-month injectable version. The best part is most people in high-risk groups can obtain PrEP for free or at a reduced cost. Read on to learn more about each method.
In addition to the amazing and lifealtering advancements that have been made in HIV treatment over the decades, there have been some huge strides in terms of HIV prevention as well. A few years back, researchers discovered that some of the drugs they had developed to treat HIV were also effective in preventing the transmission of the virus to an HIV-negative partner. This highly effective method is known as PrEP, or pre-exposure prophylaxis. When taken as prescribed, PrEP reduces the risk of getting HIV from sex by about 99 percent.
PrEP RALLY
Descovy for PrEP
Apretude (cabotegravir extended-release injectable suspension, or CAB LA) is the most recent form of PrEP approved by the Food and Drug Administration. It is gamechanging in that it is an injectable, which makes it a much more attractive option to those at risk of contracting HIV. For many, stopping by the clinic every couple of months for a shot in the booty may be a lot more convenient than trying to remember a daily pill. Unlike the pill forms of PrEP, Apretude is not also used to treat HIV. who’s it for? HIV-negative adults and adolescents (male, female, nonbinary, and transgender) weighing at least 77 pounds (35 kg) for the prevention of HIV.
dosage info: One long-acting intramuscular gluteal (butt muscle) 600 mg injection (3 mL) is given monthly for the first two months, and then one injection every two months thereafter. There are no food restrictions, and an oral lead-in period is no longer required.
In October of 2019, a second pill form of PrEP was approved by the FDA, called Descovy for PrEP (emtricitabine and tenofovir alafenamide). It is just as effective as its predecessor, Truvada. There are some differences though, so you should talk to your doctor about which might work better for you. For example, Descovy is safer for people with bone density or kidney issues, and the pill is much smaller — however, it may slightly raise LDL cholesterol levels. Also, unlike Truvada and Apretude, Descovy is not currently approved for those assigned female at birth due to a lack of research in its effectiveness.
Truvada, our great PrEP pioneer, is now celebrating its 10th year of FDAapproval. It was the fi rst medicine available in the U.S. for use to prevent HIV transmission after it was shown in studies to be highly e ff ective when taken daily. Truvada consists of the drugs emtricitabine and tenofovir. who’s it for? HIV-negative adults and adolescents (male, female, nonbinary, and transgender) weighing at least 77 pounds (35 kg). People with bone density or kidney issues should avoid and consider Descovy instead.
RANGEL/PEXELSANDERSON
Not everyone at risk of acquiring HIV may know there is an option available to prevent seroconversion (the time between exposure to a virus and when antibodies show up in your blood) after exposure to the Post-exposureHIV. prophylaxis, or PEP, is a medical option to be used in emergency situations to prevent the transmission of HIV. Emergencies that may require the use of PEP include a broken condom, recent needle sharing for intravenous drug use, or in the case of a sexual assault.
Did you know there’s medicine you can take to prevent HIV transmission after a sexual encounter?
A Morning After Pill?
dosage info: One tablet daily with food. The tablet contains 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate. Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Don’t double up on your next dose.
Truvada for PrEP
dosage info: One tablet once daily, without regard to food. The tablet contains 200 mg emtricitabine and 25 mg tenofovir alafenamide. Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Don’t double up on your next dose.
HIVPLUSMAG.COM 43
who’s it for? HIV-negative adults and adolescents assigned male at birth weighing at least 77 pounds (35 kg) for the prevention of HIV.
PEP is a combination of three drugs: tenofovir, emtricitabine (these two drugs come in one pill), and either raltegravir or dolutegravir. This combo is typically prescribed to be taken once or twice a day for about a month after exposure. The sooner after exposure PEP is started, the more effective it is. DG
For more information about PrEP and how to get a prescription, visit PlannedParenthood.org, HIV.gov, or CDC.gov/hiv/basics/prep.
Apretude
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TWO WAYS TREATMENT CAN HELP STOP HIV. Starting HIV treatment as soon as possible and sticking with it every day helps you get to and stay undetectable. That means there is so little virus in the blood that a test can’t measure it. And that’s a good thing, because: BEING UNDETECTABLE HELPS STOP THE DAMAGE HIV CAUSES. CURRENT RESEARCH SHOWS GETTING TO AND STAYING OFPREVENTSUNDETECTABLETHESPREADHIVTHROUGHSEX. There’s no cure for HIV, but if you stick with treatment, you can protect yourself and the people you care about. Talk to a healthcare provider and watch It’s Called Treatment as Prevention at YouTube.com/HelpStopTheVirus GILEAD and the GILEAD Logo are trademarks of Gilead Sciences, Inc. All other marks are the property of their respective owners. © 2020 Gilead Sciences, Inc. All rights reserved. UNBC7537 08/20