FDA advisory committee supports first drug for HIV prevention

FDA’s Antiviral Drugs Advisory Committee has recommended approval of once-daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada, Gilead Sciences) to reduce the risk of HIV-1 infection among uninfected adults, an HIV prevention strategy called pre-exposure prophylaxis or PrEP.

If FDA decides to approve Truvada for PrEP, it would be the first agent indicated for uninfected individuals to reduce their risk of acquiring HIV.

Last week members voted 19 to 3 in favor of approval for Truvada for PrEP by men who have sex with men; 19 to 2 (with 1 abstaining) in support of use by HIV-uninfected partners in serodiscordant couples; and 12 to 8 (with 2 abstaining) for use by other individuals at risk of acquiring HIV through sexual activity.

The recommendations of the advisory committee are not binding, but will be considered by FDA as the agency completes its 6-month priority review of Gilead’s supplemental New Drug Application (sNDA) of Truvada for PrEP. Gilead submitted the sNDA on December 15, 2011, and FDA has established a target review date under the Prescription Drug User Fee Act (PDUFA) of June 15, 2012.

The committee’s positive recommendation followed presentations of efficacy and safety data from several clinical studies of Truvada for PrEP, including 2 large placebo-controlled phase 3 trials sponsored by the National Institutes of Health and the University of Washington, respectively. Several other clinical studies support the use of Truvada for HIV risk reduction. In patients who took the drug as prescribed, it was more than 90% effective in preventing HIV infection, according to a Reuters report.

Truvada was approved by FDA in 2004 for the treatment of HIV-1 infection and is currently the most-prescribed antiretroviral treatment in the United States. Truvada is not indicated for HIV prevention. Its annual cost is approximately $14,000.

Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of Truvada have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and who have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

New onset or worsening of renal impairment may also occur, including acute renal failure and Fanconi syndrome. Creatinine clearance should be calculated prior to administering Truvada. Truvada should not be used by patients with severe renal disease (CrCl

Truvada should not be coadministered with any other antiretroviral agents for HIV that contain emtricitabine or tenofovir disoproxil fumarate, nor should it be coadministered with products containing lamivudine. Do not administer with Hepsera. Decreases in bone mineral density, fat redistribution, and immune reconstitution syndrome may also occur. Common side effects reported during clinical studies with Truvada (in combination with efavirenz) include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Caution should be exercised when coadministering Truvada with didanosine, atazanavir, and lopinavir/ritonavir due the potential for toxicity.