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CROI 2012: Final Partners PrEP Results Confirm Efficacy of Oral Antiretrovirals for HIV Prevention

Daily, oral pre-exposure prophylaxis (PrEP) using either tenofovir (Viread) or tenofovir/emtricitabine (Truvada) was highly effective at preventing HIV infection in a large study of serodiscordant heterosexual couples in sub-Saharan Africa, researchers reported at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this week in Seattle.

Despite the tremendous successes of antiretroviral treatment (ART), the rate of new HIV infections has remained stubbornly high. Most estimates show that for every 1 person who starts ART worldwide, 2 people become newly infected. While behavior-based interventions like condoms and needle exchange have helped slow the epidemic down, the need for new methods to reduce infection has been apparent for years.

Interest in biomedical prevention strategies has been growing rapidly. Rather than -- or in addition to -- trying to convince people to change deeply rooted behaviors, researchers and community activist have been pushing to expand the HIV prevention armamentarium to include medically based approaches. Promising results from studies of adult male circumcision and treatment as prevention have buoyed hopes that these approaches might reduce rates of new HIV infections; some even suggest they might lead to the "end of AIDS."

At CROI, Jared Baeten from the University of Washington presented final results from the Partners PrEP study, demonstrating that daily use of 1 or 2 antiretroviral drugs by HIV negative partners of HIV positive individuals reduced the risk of infection by %67 to 75%.

Partners PrEP enrolled 4758 couples in sub-Saharan Africa, in which 1 member was HIV positive while the other was HIV negative (termed "serodiscordant"). HIV negative partners were randomly assigned to take tenofovir, tenofovir/emtricitabine, or placebo. All couples were counseled about safer sex practices, given free condoms, and tested regularly for sexually transmitted infections.

Partners PrEP began enrollment in July 2008. After an interim analysis in July 2011, the study’s independent Data and Safety Monitoring Board (DSMB) recommended that the placebo arm be stopped because the 2 active drug arms showed definitive protective efficacy. All HIV negative partners in the placebo group were offered active drug, and the preliminary results were presented at the International AIDS Society meeting in Rome.

The final analysis of the primary endpoint data presented at CROI confirm the results of the earlier analysis showing that PrEP was effective and safe in this population.

Results

• There were 96 total infections seen during the study; 14 people were determined to have been HIV positive at enrollment and were not included, leaving 82 new infections in the analysis.
• 17 infections occurred among HIV negative participants in the tenofovir monotherapy arm, 13 in the tenofovir/emtricitabine arm, and 52 in the placebo arm.
• Overall, tenofovir alone was 67% effective in reducing infections, while the combination was 75% effective, both compared to placebo.
• While the majority of HIV negative partners at enrollment were men, the majority of new infections were in women.
• There were 1.49 new infections per 100 person-years among men, compared to 2.81 per 100 person-years among women.
• Adverse events were uncommon and similar across all arms.
• Approximately 10% of participants in the 2 active drug arms reported nausea 1 month after starting the drug, which was more frequent than the placebo arm; however, this rate declined to less than 4% after 3 months.
• There were few laboratory abnormalities overall, and they did not differ across arms.
• There was no evidence of drug resistance among people infected during the study.
• Self-reported unprotected intercourse declined in all arms over the course of the study, from about 27% at enrollment to less that 10% at the end of the main study period.

These results are encouraging and add to the growing body of supportive evidence for biomedical prevention. Significant issues remain unresolved, however, like who should receive PrEP, when should it be started, and who would pay for it.

While this study was done in heterosexual couples, similar results were seen in the iPrEx trial, which looked at PrEP in men and transgender women who have sex with men.

Although Baeten stressed that both PrEP strategies proved effective in both men and women, the higher rate of new infections among women are of some concern. A different PrEP study, FEM-PrEP, was halted early when no protection was seen in an interim analysis.

Some data -- including findings presented at CROI -- show that women in these PrEP studies tend to have lower drug levels than men. This is thought to be due to poorer adherence, rather than any biological mechanisms. What factors are driving the lower adherence rates among women is unclear and needs further study.  

[Jared Baetan describes findings from Partners PrEP at CROI's opening press conference on March 5, 2012]

3/7/12

Reference

J Baetan, D Donnell, P Ndase, et al. ARV PrEP for HIV-1 Prevention among Heterosexual Men and Women. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 29.