For FDA, it came down to numbers: by approving Truvada yesterday as the first drug for reducing HIV risk in people negative for the AIDS virus but prone to high-risk behaviors, the agency hopes to finally make a dent in the consistent and stubbornly high approximate figure of 50,000 adult and adolescent Americans diagnosed with new HIV infections each year.

Worse, according to CDC, infection rates among men having sex with men, especially among young minority men, have risen since 2007.

“This data shows that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country,” Debra Birnkrant, M.D., director, Division of Antiviral Products at FDA’s Center for Drug Evaluation and Research, said during a conference call with reporters.

Marketed by Gilead Sciences, Truvada reached the market in 2004 after it was approved as an HIV treatment drug. The new indication allows for the drug’s use in pre-exposure prophylaxis (PrEP), namely a comprehensive HIV prevention strategy that includes safer sex practices, risk reduction counseling, and regular testing for the virus.

In approving Truvada for HIV prevention, FDA also agreed to tighten wording on its Boxed Warning stating that Truvada for PrEP must only be used by individuals confirmed as HIV-negative prior to prescribing the drug and at least every three months during use.

Truvada for PrEP was approved with a Risk Evaluation and Mitigation Strategy focused on a training and education program to assist prescribers in counseling individuals taking or considering the drug for preventing HIV. The program will urge patients to adhere to recommended dosage and understand the risks of HIV infection while taking Truvada for PrEP, but will not restrict distribution of the drug.

FDA approved Truvada for HIV prevention based on two large clinical trials that convinced the agency of the drug’s safety and efficacy for PrEP. One 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. Truvada was effective in reducing the risk of HIV infection by 42% compared with placebo, the study showed, while efficacy was strongly correlated with adhering to the drug’s regimen. Another trial involving 4,758 heterosexual couples where one partner was HIV-infected and the other was not showed Truvada reduced the risk of becoming infected by 75% compared with placebo.

Side effects most commonly reported with Truvada PrEP included diarrhea, nausea, abdominal pain, headache, and weight loss. Serious adverse events in general, as well as those specifically related to kidney or bone toxicity, were uncommon.

FDA followed the advice of an advisory committee that in May recommended supporting expanded use of Truvada in gay and bisexual men and heterosexual couples in which one partner is HIV negative.

The panel’s recommendation emerged in three votes, each covering a different category of user, that were not unanimous. Dissenting members of the Antiviral Drugs Advisory Committee expressed concerns that some Truvada users may be lulled into a false sense of security by providing a rationale for stopping their use of condoms, while others may not follow the treatment regimen, and still others experienced liver problems.

Also raised as an issue was the percentage of black or African American women in the drug’s clinical trials: “I recognize that women in Botswana are very relevant but not necessarily to women here, who might have a very different point of view and cultural diversity and sensitivity,” committee member Marlena Vega, MSW, Ph.D., said at the panel’s May 11 meeting, according to a transcript.

Answering a GEN question during the conference call about how the advisory panel’s kidney and trial population concerns had been addressed, Dr. Birnkrant noted that Truvada’s label for PrEP was changed to add more restrictive renal function requirements, so patients who reach the indicated level of creatinine clearance are supposed to discontinue use of the drug.

Dr. Birnkrant also said the use of African trial subjects, data, and venues for the clinical trial was proper because trial sites met FDA’s standards, and the agency allows use of data from overseas clinical trials to support labeling for new indications.

“In the end, how we view Truvada for PrEP is that your exposure is in the setting of a discordant couple; whether you’re a formal discordant couple in a monogamous relationship, or you’re in a more casual relationship, nonetheless transmission occurs in the setting where one is positive and one is negative. We didn’t think that a lack of U.S. women would change that, and would change our opinion of the data we were presented,” Dr. Birnkrant said.


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