The FDA has approved oral and injectable formulations of the HIV-1 capsid inhibitor lenacapavir (Sunlenca – Gilead) for use with other antiretroviral drugs to treat multidrug-resistant HIV-1 infection (MDR-HIV) in heavily treatment-experienced adults whose current regimen is failing. Lenacapavir is the third drug to be approved exclusively for treatment of MDR-HIV; the intravenously administered CD4-directed antibody ibalizumab-uiyk (Trogarzo) and the orally administered HIV-1 gp120-directed attachment inhibitor fostemsavir (Rukobia) were approved earlier.

The severity and rapid spread of COVID-19 (caused by SARS-CoV-2) have raised questions about the use of some drugs in patients with the disease and whether currently available drugs could be effective in treating it. Definitive answers are lacking, but some recommendations can be made. For additional information on specific drugs, see our table Some Drugs Being Considered for Treatment of COVID-19.

View the Table: Treatments Considered for COVID-19

The severity and rapid spread of COVID-19 (caused by SARS-CoV-2) have raised questions about the use of some drugs in patients with the disease and whether currently available drugs could be effective in treating it. Definitive answers are lacking, but some recommendations can be made. For additional information on specific drugs, see our table Some Drugs Being Considered for Treatment of COVID-19.

The FDA has approved Dovato (ViiV), a fixed-dose combination of the integrase strand transfer inhibitor (INSTI) dolutegravir (Tivicay) and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (Epivir, and generics), as a once-daily complete regimen for treatment of adults with HIV-1 infection who are antiretroviral-treatment naive and have no known substitutions associated with resistance to either drug. Dolutegravir/lamivudine is the first complete regimen to be approved by the FDA for initial treatment of HIV-1 infection that contains 2 rather than 3 antiretroviral drugs. Juluca, a fixed-dose combination of dolutegravir and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (Edurant), was approved in 2018 for treatment of adults with HIV-1 infection already taking a stable, suppressive antiretroviral regimen.

The FDA has approved elvitegravir (Vitekta – Gilead), an integrase strand transfer inhibitor (INSTI), for use with a protease inhibitor (PI) plus ritonavir and other antiretroviral drugs for treatment of HIV-1 infection in treatment-experienced adults. Elvitegravir is also available in a fixed-dose combination (Stribild) with the pharmacokinetic enhancer cobicistat and the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir disoproxil fumarate (DF). A similar combination (Genvoya) that includes tenofovir alafenamide instead of tenofovir DF was recently approved by the FDA and will be reviewed in a future issue.

The FDA has approved Triumeq (Viiv Healthcare), a fixed-dose combination of the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine, for once-daily treatment of HIV-1 infection. Dolutegravir (Tivicay) was approved as a single agent in 2013.

The FDA has approved dolutegravir (doll-you-TEG-rah-veer; Tivicay – Viiv Healthcare), an integrase strand transfer inhibitor (INSTI), for treatment of HIV-1 infection in adults and in children ≥12 years old who weigh at least 40 kg. It is the third INSTI to be approved by the FDA; raltegravir and elvitegravir were approved earlier.

The FDA has approved crofelemer (kroe fel’ e mer; Fulyzaq – Salix), a chloride channel inhibitor derived from the red sap of the South American plant Croton lechleri, for symptomatic relief of noninfectious diarrhea in patients with HIV taking antiretroviral drugs. It is the first drug approved for relief of antiretroviral-induced diarrhea and the first oral botanical drug approved by the FDA.

The FDA has approved a fixed-dose combination of the integrase strand transfer inhibitor (INSTI) elvitegravir, the pharmacokinetic enhancer cobicistat, and the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir disoproxil fumarate (Stribild – Gilead) for treatment of HIV-1 infection in antiretroviral treament-naïve adults. Elvitegravir is the second INSTI to be approved by the FDA for use in HIV treatment; raltegravir (Isentress) was the first.

Truvada (Gilead), an oral fixed-dose combination of the antiretrovirals emtricitabine and tenofovir disoproxil fumarate frequently used for treatment of HIV infection,1 has now also been approved by the FDA for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 in adults at high risk. It is the first drug to be approved for this indication. The CDC has been recommending Truvada off-label for pre-exposure prophylaxis in men who have sex with men since 2011.2 A 30-day supply of Truvada costs about $1160.3

CLINICAL STUDIES — Approval for the new indication was based on 2 randomized, placebo-controlled trials in high-risk patients. One trial in 2,499 HIV-negative men (or transgender women) who have sex with men found that daily use of the combination reduced the risk of HIV seroconversion by 44% (36 seroconversions vs. 64 with placebo).4 A post-hoc analysis found that the rate of infection was reduced by 87.5% compared to placebo among men found to be adherent to the drug regimen (i.e., had detectable intracellular tenofovir levels).5 The second trial included 4,747 heterosexual couples among whom one partner was HIV-infected and the other was not. Truvada reduced the risk of becoming infected by 75% (13 seroconversions vs. 52 with placebo).6

RECOMMENDATIONS — Pre-exposure prophylaxis with Truvada should be considered only for persons who are at high risk for HIV-1 acquisition, are confirmed to be HIV-negative and are willing to take the drug once daily and practice safer sex. Frequent follow-up HIV antibody testing is recommended while taking the drug to ensure early diagnosis of newly-acquired HIV infection; resistance to tenofovir/emtricitabine can develop if it is taken prophylactically by patients with HIV infection.

1. Drugs for HIV infection. Treat Guidel Med Lett 2011; 9:29.

2. Centers for Disease Control and Prevention (CDC). Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep 2011; 60:65.

3. Wholesale acquisition cost (WAC). Source: PricePointRx™. Reprinted with permission by FDB. All rights reserved. ©2012. http://www.firstdatabank.com/support/drug-pricing-policy.aspx. Accessed July 25, 2012. Actual retail price may be higher.

4. RM Grant et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587.

5. FDA. Background package for NDA 21-752/supplement 30. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteeMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM303213.pdf. Accessed July 25, 2012.

6. JM Baeten et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012 Jul 11 (epub).

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Etravirine (Intelence - Tibotec), a new non-nucleoside reverse transcriptase inhibitor (NNRTI), has received fast-track FDA approval for use in combination therapy in treatment-experienced adults who have HIV-1 infection resistant to an NNRTI and other antiretroviral agents.

Raltegravir (Isentress - Merck), the first in a new class of oral HIV drugs called HIV-1 integrase strand transfer inhibitors (InSTI), has received accelerated FDA approval for use in combination therapy for treatment-experienced adults infected with HIV-1 strains resistant to multiple antiretroviral agents.

Maraviroc (Selzentry - Pfizer), the first CCR5 (CC chemokine receptor 5) antagonist has received the same FDA approval but is restricted to use in adults with CCR5-tropic HIV-1 ("R5 virus"). A commercial assay is available for R5 tropism.

The approval of new drugs and continuing concerns about drug toxicity and resistance have prompted new antiretroviral treatment guidelines. Resistance testing is not recommended before starting antiretroviral therapy. HIV infection is treated with combinations of antiretroviral drugs while monitoring the patient's HIV RNA levels ("viral load") and CD4 cell count. Increases in viral load while on therapy may indicate development of drug resistance requiring further testing and a change in treatment regimen.

Atripla (Gilead/Bristol-Myers Squibb) is the first once daily, single-tablet combination of 3 antiretroviral drugs for treatment of HIV infection. Each tablet contains 600 mg of the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva), 200 mg of the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva), and 300 mg of the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir DF (Viread). These drugs have been recommended for use together, if resistance testing confirms susceptibility, as an initial regimen of choice for treatment-na∩ve patients.

Darunavir (Prezista - Tibotec), a new protease inhibitor, has received accelerated approval from the FDA for use in combination therapy of human-immunodeficiency virus (HIV) infection in previously treated adults. It is coadministered with low-dose ritonavir (Norvir), which increases its bioavailability.