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Preparing for PrEP

PrEP (pre-exposure prophylaxis) is a new HIV prevention tool with great possibilities. Matt Sharp, who served as a community representative on the FDA panel that recommended approval of Truvada (tenofovir/emtricitabine) for PrEP, describes the vote and its implications.

[Editor's note: the FDA granted approval of Truvada for PrEP on July 16, after pushing back its deadline to September 14 in order to allow more time to develop a Risk Evaluation and Management Strategy.]

For me, Memorial Day always marks the historic AIDS Candlelight Vigil in San Francisco. Long gone are the days when the event evoked not only unbearable grief, but also impassioned anger. In earlier years the vigil usually included a march down Market Street to Civic Center, where thousands of candles would dot the quiet avenue and the foggy plaza. But today it is a much smaller memorial at Harvey Milk Plaza in the gentrified Castro district. This year’s candlelight event reminded me of the amazing progress that has been made against AIDS, and the many who were not so lucky to be alive to see the success.

One of the new developments against AIDS could be called a game-changer. PrEP represents a new prevention tool with great possibilities. Truvada, a combination pill currently used for treating HIV, was recommended for approval for HIV prevention by the FDA's Antiviral Drugs Advisory Committee on May 10. It is the first time an antiretroviral drug for HIV prevention has come under FDA scrutiny. The FDA almost always relies on the committee’s vote and stands by the recommendation.

Is this a landmark or a disaster? A game-changer or reckless? There has been a lot of rhetoric on both sides to describe PrEP. When I first heard about a pill to prevent HIV, it seemed almost obvious that an antiretroviral drug would work to prevent HIV infection, as it is so effective as treatment and penetrates into genital mucosal tissue. But the 12 and a half hour advisory panel proved to be a handwringer due to several complicated issues regarding implementation.

The panel was charged with assessing the risks versus benefits of Truvada PrEP based on 3 large randomized controlled clinical trials in men who have sex with men and transgender women (iPrEx) and in heterosexual men and women (Partners PrEP and TDF2).

In what was my second FDA advisory committee this year -- the first involving an incredibly conflicted vote for me -- I found these data convincing enough to affirm that the benefit of Truvada PrEP outweighed the risk. At the end of the committee meeting, most panelists agreed to recommend approval.

As one of 3 community members on the panel, I clearly understand the risks with this new prevention tool, but my affirmative vote was a reflection of the evidence presented, and not about projections, unknowns, and fears that may or may be part of "real world" use of PrEP. I also know that my community desperately needs a change in the rate of new infections, and with dedicated funding, public health support, and community assistance, this prevention tool will at the very least contribute to reducing HIV incidence in the U.S. While the AIDS Healthcare Foundation -- the main opponent of Truvada PrEP -- stacked the public testimony with naysayers,  those speaking in favor were from a variety of organizations.

The following were contentious issues:

• Drug resistance in the case of HIV transmission that occurs while using Truvada is an important concern. But it was seen only once during the trials, and that one participant was able to be effectively treated afterward.

• Side effects, as with any drug used for prevention or treatment, are a real concern with Truvada, especially with its history of kidney toxicities in people with HIV. As is the case with HIV positive patients considering treatment, people with existing kidney problems should not use Truvada for PrEP. Longer-term side effects such as bone toxicity are unknown.

• Truvada effectiveness was highest in people who adhered to daily dosing in the trials, who made up around 10% of participants. In the real world there will need to be ongoing support to hammer home the importance of a daily dose to maintain HIV prevention effectiveness. One day there will be better drugs with different delivery methods to use for PrEP. I liken Truvada for prevention to AZT as first drug for HIV treatment, and look how many better options exist now.

• Rates of other sexually transmitted infections -- which increase the risk of HIV infection -- were low due to ongoing support, testing, and care during the trials. Since condoms are not used in many situations today, Truvada would at least provide a degree of protection. In the real world there will have to be major efforts in counseling and testing in order to help people understand that PrEP is not a magic pill and should be used along with condoms and other safer sex practices.

The FDA requires a Risk Evaluation Mitigation Strategy, or REMS, that will be used to monitor people using Truvada for PrEP in the real world and should help address these issues. The REMS is a more detailed education and communication guide added to the drug labeling that will inform patients and providers about safe usage of the product. While much remains to be tackled in making this program work, the panelists felt that effective REMS would support the approval of Truvada.

PrEP has been big news on all fronts in recent years, and it has been controversial since clinical trials were first announced over 9 years ago. But the truth is that we can only hope that PrEP will provide an additional intervention against HIV, especially in high-risk communities.

There is much more work to be done on a community level to unravel ongoing concerns, but the science is clear. Based on controlled clinical trials, Truvada is safe and effective for PrEP in a variety of higher-risk populations. We owe people at risk another option where older prevention tools are just not working. Until other new strategies can be employed, PrEP may be what tips the balance in a favorable direction towards the goal of ending AIDS.

5/23/12