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IAS 2011: Final iPrEX Analysis Confirms PrEP Effectiveness for Gay Men

Pre-exposure prophylaxis (PrEP) was shown to be highly effective for men and transgender women who have sex with men in a completed analysis of the large iPrEx trial presented at IAS 2011, but the prevention effect was blunted by low levels of adherence.

Biomedical approaches to preventing HIV infection have received increased attention over the past few years. Strategies like treatment-as-prevention, vaginal and anal microbicides, and adult male circumcision have spurred interest in an effort to diversify the armamentarium of prevention tools and have blurred -- if not obliterated -- the distinction between HIV prevention and treatment.

As described in an oral presentation a the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) last week in Rome, final results from the iPrEx trail showed oral PrEP to be effective for men who have sex with men (MSM) and transgender women. This analysis largely confirmed results already presented from preliminary analyses of this landmark study.

This randomized, controlled clinical trial enrolled a total of 2499 MSM and transgender women at 11 sites on 4 continents. Participants were randomly assigned to take either tenofovir/emtricitabine (Truvada) PrEP or a matching placebo once daily. All participants were counseled about safer sex practices, provided with free condoms, and tested for HIV infection every 12 weeks.

Results

• There were 132 infections in the study -- 84 in the placebo arm and 48 in the tenofovir/emtricitabine PrEP arm.
• 35 infections were averted, indicating that PrEP was 42% effective in an overall intent-to-treat analysis.  
• PrEP was 92% effective, however, among participants with detectable drug in their blood, showing very high efficacy for people who were adherent to the study protocol.
• A sub-study revealed significant regional differences in adherence.
• Analysis of drug detection in hair samples found 90% adherence in the U.S. and South Africa, compared to 55% in South America and Thailand.   
• Self-reported frequency of unprotected receptive anal intercourse decreased by roughly 50% in both arms of the study.
• This remained true when looking at participants who believed they were receiving PrEP rather than placebo.

The next step for this trail is an open label extension, which will provide post-trial PrEP for all interested participants. It will evaluate implementation issues, PrEP uptake, changes in sexual practices, and the need for follow-up evaluation.

Results from 2 other PrEP studies were also presented at IAS. TDF2 looked at PrEP use in heterosexuals while Partners PrEP evaluated serodiscodant mostly male-female couples. Both studies showed significant reductions in new HIV infections for people taking tenofovir with or without emtricitabine.

However, another such study -- called FEM-PrEP -- was recently halted after an interim analysis showed no protective effect for women in Africa. In total, therefore, 3 recent studies of PrEP have demonstrated significant efficacy and 1 has not. Further analyses from FEM-PrEP may help explain its discrepant results.

Robert Grant from the Gladstone Institute in San Francisco said iPrEx shows that PreP has “demonstrated safety and a high level of protection among people who are able to use it.”

The importance of adherence to PrEP should not be overlooked. iPrEx, TDF2, and Partners PrEP all found large differences in efficacy depending on participants' adherence to the study protocol.

While these 3 studies strongly suggest PrEP works very well in people who take

it regularly, they also show that many struggle to do so and that PrEP offers much less protection for these people. A fuller understanding of the factors that predict adherence will be crucial in any effort to expand the use of PrEP.

Some have expressed fear that PrEP might lead to "disinhibition" among study participants, causing them to have more unsafe sex or reduce condom use if they believe they are protected. This fear has been expressed regarding other prevention modalities, including needle exchange, adult male circumcision, and treatment-as-prevention.

Importantly, no such increases in risk-taking behavior were seen in iPrEx. The same was the case in both TDF2 and Partners PrEP. In fact, the opposite was seen in each of these studies -- risk behavior has decreased with each of these interventions.

Some people are calling IAS 2011"Vancouver of Prevention," comparing it to the watershed 1996 International AIDS Conference where the first data on highly active antiretroviral therapy (HAART) were presented. The past few years have indeed seen very encouraging results for biomedical approaches to HIV prevention, including PrEP, circumcision, topical microbicides, and treatment-as-prevention. The iPrEx final results presented in Rome contribute to the growing sense of optimism that these new tools might go a long way toward stemming the tide of new HIV infections. 

[Click here for an HIVandHepatitis.com video interview with iPrEx lead investigator Robert Grant]

7/29/11

References

R Grant, V McMahan, A Liu, et al. Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract WELBC04.

A Liu, Y Huang, P Defechereux, et al. Hair as a biological marker of daily oral pre-exposure prophylaxis (PrEP) adherence and tenofovir/emtricitabine (TFV/FTC) exposure in the Global iPrEx Study. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract MOLBPE037.

H Gilmore, A Liu, KR Amico, et al. Adherence/drug detection rates and study participant experiences of counseling support among MSM in the iPrEx pre-exposure prophylaxis (PrEP) trial in San Francisco, United States. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. Abstract TUPE363.