1. Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
- Author
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McKinnon LR, Liebenberg LJ, Yende-Zuma N, Archary D, Ngcapu S, Sivro A, Nagelkerke N, Garcia Lerma JG, Kashuba AD, Masson L, Mansoor LE, Karim QA, Karim SSA, and Passmore JS
- Subjects
- Cytokines metabolism, Female, Genitalia, Female drug effects, Genitalia, Female virology, HIV Infections pathology, Humans, Inflammation pathology, Multivariate Analysis, Tenofovir pharmacology, Treatment Outcome, Genitalia, Female pathology, HIV Infections drug therapy, HIV Infections virology, Inflammation drug therapy, Tenofovir therapeutic use
- Abstract
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.
- Published
- 2018
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