FDA approves HIV prevention pill

UNITED STATES – The US Food and Drug Administration (FDA) has approved a single-pill combination drug to reduce the chance of acquiring HIV among people at high risk for infection with the virus.

In two large clinical trials, the combination of tenofovir and emtricitabine, marketed as Truvada and taken daily, reduced the rate of infection among men who have sex with men and in heterosexuals, the agency noted in announcing the approval.

While anti-HIV drugs have been used for years to prevent infection of infants born to HIV-positive mothers, Truvada is the first indicated specifically for so-called pre-exposure prophylaxis, or PrEP, the agency said.

It was previously approved for treatment of HIV in adults and children 12 or older, and an FDA advisory panel endorsed the new indication in May.

The new indication means the drug combination is “part of a comprehensive HIV prevention strategy that includes other prevention methods, such as safe sex practices, risk reduction counseling, and regular HIV testing,” the FDA said.

The approval is “an important milestone in our fight against HIV,” said FDA Commissioner Margaret Hamburg, MD.

Hamburg noted in a statement that about 50,000 Americans are diagnosed with HIV infection yearly. “New treatments as well as prevention methods are needed to fight the HIV epidemic in this country,” she added.

The approval comes with some caveats, mainly to prevent the development of genetic resistance to the drug combination:

• The FDA is changing Truvada’s boxed warning to ensure that both doctors and potential users know that the drug must only be used for PrEP by people who are confirmed to be HIV-negative before the drug is started.
• Those using the drug combination must be tested for HIV and shown to be negative at least every 3 months during use.
• The combination is also subject to a Risk Evaluation and Mitigation Strategy (REMS), whose central component is a training and education program to assist prescribers in counseling users or potential users.
• And the manufacturer, Gilead Sciences, of Foster City, Calif., is required to collect viral isolates from individuals who acquire HIV while taking Truvada and to evaluate these isolates for the presence of resistance.
• The company is also required to collect data on outcomes for women who become pregnant while taking Truvada for PrEP.
• Gilead has also been told to conduct a trial to evaluate drug adherence and its relationship to adverse events, risk of acquiring HIV, and development of resistance among those who become HIV-positive.

Resistance to HIV drugs often arises when fewer than three different drugs are taken for treatment. The concern with PrEP is that some people may catch HIV, continue taking Truvada rather than a complete three-drug regimen, and develop resistance.

The combination has been tested for PrEP in several clinical trials, but the agency considered two main studies — the iPrEx trial evaluated Truvada in 2,499 HIV-negative men or transgendered women who have sex with men, and the Partners PrEP trial was conducted in 4,758 heterosexual couples where one partner was HIV-infected and the other was not.

Final results of Partners PrEP were reported July 11, as well as two other studies of the topic – the FEM-PrEP and TDF2 trials – and a Cochrane review that found that, despite some equivocal results, using either the combination or tenofovir alone for PrEP was both safe and effective.

Despite those findings, the notion of PrEP has been controversial to some degree, not least because it has the potential to divert resources from treatment.

For instance, the HIV Medicine Association – which includes many of the most prominent HIV clinicians in the U.S. – said it supports the new indication but added it “must not contribute to HIV-related healthcare disparities,” according to chair Judith Aberg, MD, of NYU Langone Medical center in New York City.

In particular, Aberg said in a statement, financial support for safety-net programs, such as the Ryan White program, should not be diverted to PrEP.

Some experts have also suggested that using Truvada for PrEP might hamper efforts to treat more infected people in a tight economy.

In the wake of last week’s major publications, Robert Schooley, MD, of the University of California San Diego, said a key issue is how well the results of clinical trials will translate into the real world.

“The difficulty is in envisioning how one would extrapolate the study results to the larger community,” he said in an email, adding it’s “difficult to envision” how PrEP would work in a cash-strapped healthcare system.

Others have noted that – at least in heterosexual couples – treating the infected partner reduces the risk of transmission by about 95%, markedly higher than the results in either of the major PrEP trials.

Former International AIDS Society president Julio Montaner, MD, of the University of British Columbia in Vancouver, has been one of those arguing in favor of expanded treatment rather than PrEP.

“The best, most solid investment in stopping the epidemic is to invest in treatment now, massively, as much as we can,” Montaner told MedPage Today at the Rome meeting of the International AIDS Society in 2011.

PrEP, he said, is likely to have a role only as a “very targeted” approach, aimed at people who are at high risk and, for some reason, can’t control their exposure to the virus.

Category: Pharmaceuticals