More PrEP Data and Discussion

It's fair to say that this year's 18th Conference on Retroviruses and Opportunistic Infections (CROI) was dominated by discussion about pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) to prevent HIV infection. This is not all that surprising given that last year two trials demonstrated the first efficacy of PrEP using ARVs in either a pill or topical gel format.

The study of oral PrEP, known as iPrEx, evaluated the efficacy of Truvada, a combination of the ARVs  tenofovir (TDF) and emtricitabine (FTC), in a cohort of nearly 2,500 men and trasgendered women who have sex with men at 11 clinical trial sites.

On Tuesday at CROI, investigators presented several additional analyses of the iPrEx trial data.iPrEx principal investigator Robert Grant of the University of California, San Francisco, provided data from an additional six months of follow up that showed the protective effect of Truvada was durable. The initial findings from iPrEx showed the regimen was 44% effective in reducing HIV acquisition through May 1, 2010. This latest round of data collected through November 2010 showed that daily Truvada use resulted in a slightly lower, but still statistically significant efficacy of 42%. Grant said drug detection tests showed that the the new infections were correlated with low adherence. "It was protective when used and not protective when not used," said Grant.

To better understand factors that influence adherence, the iPrEx Study Group is launching an open label study (one that is unblinded) that will begin over the next few months at iPrEx sites and will offer the TDF-FTC combination to every HIV-uninfected participant from the iPrEx study. Grant said the intent of the open label study is to see what impact PrEP will have on behavior when participants know they are taking a drug that can protect them from HIV infection. The study will also continue to assess long-term safety of Truvada in healthy volunteers.

Researchers also reported findings from two separate studies—one a subanalysis of iPrEx and another from a safety study of PrEP in 400 HIV-uninfected men who have sex with men (MSM) in the US—that showed a small but statistically significant drop in bone mineral density, a side effect seen in some HIV-infected individuals treated with Truvada, among HIV-uninfected men who received PrEP drugs compared to those who did not. The declines in bone mineral density—a marker for bone fractures—ranged from 0.7% to 1.1% in the two studies. Neither study saw an increased rate in bone fractures among volunteers receiving PrEP, but more long-term data is necessary to fully assess this side effect.

Findings were also presented from a sub-analysis of iPrEx data that showed no drug-resistant HIV was present in volunteers who became HIV infected despite receiving Truvada. "We looked much more closely for drug resistance and didn't find it," said Grant. This is good news—development of drug-resistant HIV was one of the biggest concerns affiliated with PrEP because these drugs are also widely used to treat HIV. "Many people's concerns about resistance have been largely allayed," said Connie Celum of the Unviversity of Washington.

Now that questions about resistance have been allayed, a series of new questions seems to be occupying the minds of HIV prevention researchers and advocates. One question is how to use Truvada for PrEP. "We need to start thinking about how to do this," said Celum. Even though the US Centers for Disease Control and Prevention released interim guidance for physicians on the use of PrEP, it doesn't seem too many physicians have started prescribing Truvada for prevention. "I don't get the sense that a lot of clinicians are ready to deal with this yet," added Celum. And so far it doesn't seem that MSM in the US are clamoring for the prevention pill.

Last night AVAC and Fenway Community Health co-hosted a discussion on PrEP at the Fenway community clinic, a gleaming new building in the shadow of the green monster. At this event, several panelists discussed how PrEP should be used and how much of an issue adherence will be with any behaviorally dependent intervention. "The criteria for starting PrEP should be someone who asks for it," said Grant. "PrEP is not for everyone."

As for adherence, Grant challenged the notion that adherence will always be higher in a clinical trial. He thinks that adherence will likely be higher when volunteers are told they are receving Truvada, and that it was shown to be effective in protecting against HIV only when taken reliably. "Adherence is a solvable problem," said Grant.

-written by Regina McEnery and Kristen Jill Kresge