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An interim review from the VOICE study — a large, randomized trial evaluating oral and topical antiretroviral-based approaches to HIV pre-exposure prophylaxis (PrEP) in women — has indicated that continued evaluation of daily oral tenofovir is futile in this population, because the study will not be able to demonstrate whether the drug is effective. Notably, the review did not identify any safety concerns.
The VOICE trial originally included five study arms — oral tenofovir (Viread), oral tenofovir/FTC (Truvada), oral placebo, vaginal tenofovir gel, and vaginal placebo gel — with each intervention prescribed for daily use. About 1000 HIV-uninfected women were assigned to each arm. Those receiving oral tenofovir are now being asked to discontinue that study medication, while all others continue as planned. The trial is expected to be completed before the end of 2012.
NIH modifies ‘VOICE' HIV prevention study in women [press release]. Bethesda, MD: National Institute of Allergy and Infectious Diseases; Sep 28, 2011. (http://www.nih.gov/news/health/sep2011/niaid-28.htm)
Comment
The various PrEP trial results released in the past year have been cause for both excitement (in the case of iPrEx, Partners PrEP, and TDF2) and disappointment (in the case of FEM-PrEP and now VOICE) — and have consequently led to much confusion, particularly in terms of understanding the efficacy of oral PrEP in women.
Pharmacokinetic data presented at CROI this year (Abstracts 34LB and 35LB) suggest that vaginal levels of orally administered tenofovir in women are lower than rectal levels of orally administered tenofovir in men, which could explain the discrepant results between iPrEx and FEM-PrEP. Experts have also suggested that there could be a pharmacokinetic interaction between antiretrovirals and hormonal contraceptives — and that adherence and/or drug diversion could be responsible for some of the findings. However, without complete data from any of the oral PrEP trials that included women, interpreting the results is extremely difficult. For now, we can at least be reassured by the fact that the data and safety monitoring board for the VOICE trial is allowing the oral tenofovir/FTC arm to continue.
Understanding the limitations of the available randomized studies, as well as their subtle details, will be critical to the success of efforts that are unfolding to operationalize PrEP in high-incidence communities. Until such understanding is more complete, demonstration projects of oral PrEP will likely be limited to the populations studied in iPrEx: men who have sex with men (MSM) and transgender women.