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Nat Med. 2018 May;24(4):491-496. doi: 10.1038/nm.4506. Epub 2018 Feb 26.

Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.

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Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa.
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Eschelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.
Department of Epidemiology, Columbia University, New York, New York, USA.
National Health Laboratory Service, Cape Town, South Africa.


Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at >2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts.

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