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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • Female
  • Genitalia, Female / drug effects
  • Genitalia, Female / pathology*
  • Genitalia, Female / virology
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / virology*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Multivariate Analysis
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use*
  • Treatment Outcome

Substances

  • Cytokines
  • Tenofovir