By David Liu, PHD

Saturday July 21, 2012 (foodconsumer.org) -- The FDA has agreed that Gilead Sciences, Inc. based out of Foster City, California can market its antiretroviral drug Truvada (emtricitabine) in the U.S. for the prevention of HIV transmission.

Truvada has already been approved since 2004 as a treatment for those who are already infected with the HIV. But this is the first time that the FDA allowed an anti-HIV treatment to be used for pre-exposure prophylaxis, or PrEP.

The FDA approval which was announced on July 16 was based largely on two randomized, double-blind, placebo-controlled clinical trials. 

The FDA stated:

The iPrEx trial evaluated Truvada in 2,499 HIV-negative men or transgender women who have sex with men and with evidence of high risk behavior for HIV infection, such as inconsistent or no condom use during sex with a partner of positive or unknown HIV status, a high number of sex partners, and exchange of sex for commodities. Results showed Truvada was effective in reducing the risk of HIV infection by 42 percent compared with placebo in this population. Efficacy was strongly correlated with drug adherence in this trial.

The Partners PrEP trial was conducted in 4,758 heterosexual couples where one partner was HIV-infected and the other was not (serodiscordant couples). The trial evaluated the efficacy and safety of Truvada and tenofovir versus placebo in preventing HIV infection in the uninfected male or female partner. Results showed Truvada reduced the risk of becoming infected by 75 percent compared with placebo.

The food and drug agency did not mentioned any trial that failed to demonstrate the efficacy of Truvada for the HIV prevention. It remains unknown whether the drug maker has informed the FDA in its petition of trials that disproved the efficacy of Truvada in the first place. 

At least one study showed that  once-daily oral TDF–FTC among high-risk women in Africa did not reduce the risk of HIV transmission among African women who were at high risk for HIV infections.  TDF-FTC refers to the treatment regimen called "daily oral preexposure prophylaxis with 300 mg of tenofovir disoproxil fumarate (TDF), an oral prodrug of tenofovir, alone or in combination with 200 mg of emtricitabine (FTC)" as the authors described.

The Preexposure Prophylaxis Trial for HIV Prevention among African Women (FEM-PrEP), a randomized, double-blind, placebo-controlled trial led by Lut Van Damme, M.D. and other 28 medical researchers and published prior to the FDA approval on July 11 in the prestigious medical journal the New England Journal of Medicine.  The trial was terminated early on April 18, 2011 because of a lack of efficacy, the authors reported.

The study was designed to test the hypothesis that once-daily TDF_FTC is greater than 30 percent effective in preventing HIV acquisition.  But the expected outcome did not show up in the trial.

Sixty eight cases of  HIV infections among 3,900 African-women were identified during the trial.  The incidence rate among the study group that received the HIV prevention treatment was 4.7 per 100 person-years, compared to 5.0 per 100 person-years among the control group.  The hazard ratio in the treatment group was 0.94, indicating that the difference in the incidence rates is statistically insignificant.

Lut Van Damme et al. concluded "prophylaxis with TDF–FTC did not reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo."

But the researchers are cautious in interpreting the outcomes of their trial.  They wrote in their study report that "we were unable to accurately assess the effect of TDF–FTC on HIV acquisition or safety because of low study-drug adherence, which may be an indication that a daily pill-taking regimen will be difficult for some populations."

The FDA in its announcement also acknowledged that the use of Truvada resulted in side effects including diarrhea, nausea, abdominal pain, headache, and weight loss, but severe adverse effects and those related to kidney and bone toxicity were uncommon.

Although Truvada seems to have some protective effect against HIV infections, it is questionable whether the prevention measure is worth taking considering treatment adherence can be a problem and the protection for an individual is largely uncertain.   Because of this, men and women who practice unsafe sex should not solely count on this drug to prevent HIV infections.