• Journal Article

Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention

Citation

Van Der Straten, A., Van Damme, L., Haberer, J. E., & Bangsberg, D. R. (2012). Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention. AIDS, 26(7), F13-F19. DOI: 10.1097/QAD.0b013e3283522272

Abstract

While the balance of recent evidence supports the efficacy of antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) against HIV-1 infection, recent negative trial results are perplexing. Of seven trials with available HIV endpoints, three different products have been tested: tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF) tablets, and TDF/emtricitabine (TDF/FTC or Truvada) tablets. Six of these trials were conducted exclusively in sub-Saharan Africa; all found the products to be safe, and four (CAPRISA004; iPrEX; Partners for PrEP; TDF2) demonstrated effectiveness. Furthermore, HPTN 052 recently confirmed that ARV treatment leads to 96% reduction in transmission to HIV-negative partners in HIV-serodiscordant couples. These results, along with human and animal data, provide substantial evidence for the efficacy of ARV-based HIV prevention. Yet assessment of oral Truvada in the FEM-PrEP study and of oral and vaginal tenofovir in the VOICE study was stopped for futility. How do we make sense of these discrepant results? We believe that adherence is a key factor, although it cannot be the only factor. Expanding upon a recent editorial in the Lancet, we discuss the impact of suboptimal product adherence on PrEP efficacy in the context of variable drug concentration at the exposure site, integrity of the vaginal epithelium, and the role of acute infection