The FDA has approved Descovy (Gilead), a fixed-dose combination of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC) and tenofovir alafenamide (TAF) for use with other antiretroviral agents for treatment of HIV-1 infection. A combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF; Truvada) has been available since 2004 for the same indication. Emtricitabine and TAF are also available in combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine as Odefsey and with the integrase strand transfer inhibitor (INSTI) elvitegravir plus the pharmacokinetic enhancer cobicistat as Genvoya.

Antiretroviral therapy is recommended for all HIV-infected patients, both to reduce the risk of disease progression and to prevent transmission of the virus to others. Various guidelines for treatment of HIV infection are available.

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 drugs of choice for treatment of viral infections (other than HIV) and their dosages are listed in Tables 1-6 on the pages that follow. Some of the indications and dosages recommended here have not been approved by the FDA. Vaccines used for the prevention of viral infections are discussed elsewhere.

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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Guidelines for use of antiretroviral agents continue to shift toward earlier and more continuous treatment, both to treat the patient and to prevent transmission of the disease to others. Resistance testing is now recommended when antiretroviral drugs are started. Increases in HIV RNA levels ("viral load") while on therapy may indicate development of drug resistance, requiring further testing and a change in the treatment regimen. Antiretroviral drugs interact with each other and with many other drugs; complete information on these interactions is available at www.aidsinfo.nih.gov.

New guidelines for use of antiretroviral agents have been published, with a shift towards earlier and more continuous treatment. HIV infection is treated with combinations of antiretroviral drugs depending on the patientÆs 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. Resistance testing is now recommended when a patient is first seen, regardless of when therapy will be started.

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.

The FDA has approved emtricitabine/tenofovir (Truvada - Gilead) and abacavir/lamivudine (Epzicom - GSK), two new fixed-dose combinations of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), for once-daily use in treatment of HIV infection. Two other fixed-dose NRTI combinations were previously approved for twice-daily dosing. Dual NRTI therapy is generally used in either an NNRTI (non-nucleoside reverse transcriptase inhibitor)-based or a PI (protease inhibitor)-based regimen.