by Tim Horn
In a series of votes by the U.S. Food and Drug Administration’s Antiviral Drugs Advisory Committee, Truvada (tenofovir plus emtricitabine) has been recommended for approval as the first prescription drug—to be used daily and in conjunction with condoms and other safer-sex measures—to prevent HIV among those at risk for the infection.
At a May 10 meeting on the FDA’s White Oak Campus in Silver Spring, MD, which lasted more than 12 hours, the strongest vote—19 in favor and three against—was to recommend approval for men who have sex with men (MSM) at risk for HIV. A similar vote—19-2, with one abstention—resulted in Truvada being recommended as as pre-exposure prophylaxis (PrEP) for HIV-negative partners in serodiscordant relationships. The closest vote—12 in favor and eight against, with two abstentions—was for other individuals at risk for acquiring HIV through sexual activity.
Though the FDA is not required to follow the approval recommendations of its independent advisory committees, it usually does so. The agency is expected to announce its decision on or before June 15, which will likely reflect other key discussion points at the May 10 meeting, including the frequency of HIV testing and safety assessments for individuals using Truvada as PrEP, Gilead’s proposed strategies to minimize risks associated with Truvada as PrEP and any post-approval study requirements.
During a contentious public comment period, in which roughly 50 activists and health care professionals testified, the majority argued against the approval of Truvada as PrEP, based on efficacy and safety concerns.
Michael Weintstein, who founded and currently heads the Los Angeles-based AIDS Healthcare Foundation, an organization that has waged a long-standing campaign against GIlead’s PrEP approval request, likened the situation to the U.S. government’s Tuskegee syphilis experiment—designed to study the progression of untreated syphilis in poor, rural black men—and said that FDA approval “would be a reckless act.”
Several people did testify in favor of approval, based on safety and efficacy data reported previously and fully summarized at the May 10 meeting. “We need additional tools in our prevention toolbox,” explained Richard Elion, MD, of the Whitman Walker Clinic in Washington, DC. “We are not winning the battle. We’re asking for a modality that’s still being developed to be added to our toolbox.”
“The only way we are going to end the epidemic is through a combination approach,” said Susan Buchbinder, MD, of the San Francisco Department of Health, in a scheduled overview of existing HIV prevention strategies at the start of the meeting. Noting that condoms are not 100 percent effective—in part because of improper use and breakage—and that behavioral intervention strategies aren’t universally successful, she explained that what’s needed “are new treatments and prevention strategies to have a major impact on the US epidemic.”
Specific concerns raised by those offering public testimony, by those for and against approval, and the advisory committee panel—which included HIV-treating clinicians, researchers and three consumer representatives—included the need for daily adherence, which was a problem in many of the clinical trials conducted to date. Other worries included the risk of drug resistance emerging in those who become infected while using the drug and the known side effects of Truvada, notably kidney damage and bone loss.
Whether Truvada as PrEP is associated with significant safety issues has not been fully determined. Though several placebo-controlled clinical trials have been conducted, HIV infections and serious side effects while receiving Truvada have been rare. Additional research, including well-designed feasibility studies, are needed to allow for a more complete assessment of Truvada’s risks and benefits as an HIV prevention strategy.
Numerous data sets from the clinical trials were reviewed by the advisory committee, including results from the National Institutes of Health (NIH)-funded international iPrEx study; the University of Washington’s Partners PrEP study conducted in Kenya and Uganda; the U.S. Centers for Disease Control’s TDF2 safety study conducted in Botswana; Family Health International’s FEM-PrEP study conducted in Kenya, South Africa and Tanzania; and the NIH VOICE study conducted in Uganda, South Africa and Zimbabwe.
Results from iPrEx were used to support the approval recommendation for MSM. In that study, involving roughly 2,500 MSM at risk of HIV, Truvada PrEP was associated with an average 44 percent reduction in the risk of HIV infection, compared with those who took placebo. Among the 10 percent of study participants who used the drug at least 90 percent of the time, the risk reduction was 73 percent.