FDA Panel OKs Truvada for HIV Prevention

Truvada, a once-daily antiretroviral pill, is effective for preventing sexual transmission of HIV and should be approved as post-exposure prophylaxis, or PrEP, a Food and Drug Administration advisory committee voted last week.

"We don't know how PrEP will work in the real world, but at this point the benefits of people taking a pill to prevent HIV transmission outweigh any risk in clinical trials to date," said Matt Sharp, who served as a community representative on the committee. "Given the critical need to reduce new infections - especially among gay men, where the numbers have remained flat - I don't see how we cannot get behind PrEP."

Truvada, produced by Foster City-based Gilead Sciences, contains two drugs, tenofovir and emtricitabine, that are among the most widely used medications for HIV treatment. The combination has also recently been shown to dramatically reduce the risk of HIV sexual transmission in different population groups.

The FDA's Antiviral Drug Advisory Committee voted decisively in favor of approving Truvada PrEP for the most extensively studied groups, men who have sex with men (19-3) and HIV-negative partners in serodiscordant couples (19-2). The vote was closer for others at risk of acquiring HIV through sex (12-8).

Promising data

Gilead requested approval for Truvada PrEP in December based on evidence from large clinical trials showing that it can lower the risk of becoming infected with HIV if taken regularly. In all studies participants also received risk-reduction counseling and were encouraged to use condoms, which were provided free.

The iPrEx trial, which enrolled nearly 2,500 gay and bisexual men and a small number of transgender women in six countries (including San Francisco and Boston in the U.S.), found that daily Truvada reduced the risk of acquiring HIV by 42 percent overall, rising to 92 percent for participants who had drug levels in their blood indicating good adherence.

Two other large trials conducted in Africa - Partners PrEP and TDF2 - showed that the drugs in Truvada reduced the risk of HIV infection among heterosexual men and women by 60 percent to 75 percent, again rising among those who took it as directed.

The Fem-PrEP study of daily Truvada for African women did not demonstrate a protective effect, but further analysis showed that participants' blood drug levels were low despite self-reported good adherence.

"PrEP offers a new prevention tool for those most at risk for HIV, and should be provided in the context of other prevention strategies, including HIV and [sexual transmitted infection] testing, condoms, and with adherence support," Partners PrEP principal investigator Connie Celum told the Bay Area Reporter. "To turn the tide on the HIV epidemic in the U.S. and globally, we need to be guided by evidence in developing our approach to HIV prevention."

"The meeting and vote represent a tremendous milestone for HIV prevention," added Partners PrEP medical director Jared Baeten. "While implementing PrEP will face logistical and financial challenges, it is imperative to determine how this effective prevention strategy can be made available to those at greatest risk worldwide."

Reaction mostly positive

While Truvada PrEP appears highly effective when used consistently as part of a comprehensive prevention approach, some advocates have raised concerns about the difficulty of ensuring good adherence, long-term side effects - especially bone and kidney problems associated with tenofovir - drug resistance, reduced emphasis on safer sex, and cost and access issues.

"I believe it will result in less condom use and more infections," cautioned AIDS Healthcare Foundation President Michael Weinstein. "There's no reason for somebody to use condoms if they are taking this medication. They wouldn't be taking heavy-duty chemotherapy if they intended to practice safe sex."

But most other advocates applauded the committee's decision.

"It is easy, but somewhat naive, to say that people should just try harder to use condoms to prevent HIV," Project Inform Executive Director Dana Van Gorder said. "We must give people at risk for HIV the ability to choose for themselves which proven prevention methods are most likely to respond to their needs in the effort to remain HIV-negative."

Project Inform and a coalition of other advocacy groups urged the Centers for Disease Control and Prevention and other public health agencies to quickly issue guidance on the appropriate use of Truvada PrEP for different populations. They also stressed the need for demonstration projects - like one currently in the works in San Francisco - to study real-world PrEP use in high-risk groups such as young black gay men.

"After more than a decade of research we are tantalizingly close to having the first new effective HIV prevention tool in 30 years," stated Project Inform research director David Evans. "We must deploy it as quickly, but safely, as possible."

"We can now envision the end of AIDS transmission in the world," iPrEx principal investigator Robert Grant told the B.A.R. , "not just because of PrEP, but because of the combination of different ways we can offer for helping people stay free of HIV."

The FDA is expected to make a decision about approval of Truvada PrEP by June 15; the agency is not required to follow committee recommendations, but it usually does so.

Other FDA action

Last week was a big week for Gilead, as the Antiviral Drugs Advisory Committee also approved the company's latest all-in-one antiretroviral regimen, known as the Quad. A final decision in expected by late summer.

Clinical studies showed that the Quad - which contains the integrase inhibitor elvitegravir, the new "booster" cobicistat, and tenofovir/emtricitabine - was as effective as the widely used Atripla pill (also made by Gilead) and the popular protease inhibitor atazanavir (Bristol-Myers Squibb's Reyataz), but caused fewer side effects. Some experts, however, worry about possible kidney toxicity from cobicistat, especially when used in combination with tenofovir.

In related news, the FDA's Blood Products Advisory Committee on Monday, May 14 unanimously recommended approval of the OraQuick In-Home HIV Test. If granted final approval, it will be the first over-the-counter HIV test that can be used without participation of medical professionals or trained counselors. (A currently available test allows people to take a sample at home and send it to a laboratory for analysis; the new test will provide results directly.)

Committee members expressed concern about false-negative and false-positive results, but ultimately decided that the test was safe and effective, and that the benefits of more people learning their HIV status outweigh the potential risks.