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

Details

• Alternative Title:
  Nat Med
• Personal Author:
  McKinnon, Lyle R. ; Liebenberg, Lenine J. ; Yende-Zuma, Nonhlanhla ; Archary, Derseree ; Ngcapu, Sinaye ; Sivro, Aida ; Nagelkerke, Nico ; Lerma, Gerardo Garcia ; Kashuba, Angela D. ; Masson, Lindi ; Mansoor, Leila E. ; Karim, Quarraisha Abdool ; Abdool Karim, Salim S. ; Passmore, Jo-Ann S.
• Description:
  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.
• Subjects:
  Article
• Source:
  Nat Med. 24(4):491-496.
• Pubmed ID:
  29480895
• Pubmed Central ID:
  PMC5893390
• Document Type:
  Journal Article
• Funding:
  R01 AI111936/AI/NIAID NIH HHS/United States
• Volume:
  24
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6ec2dbcf3bf12aef5c64e2308d20b381cee8e92fd34fe4aaaeba410e6e9ec18b
• Download URL:
  https://stacks.cdc.gov/view/cdc/59269/cdc_59269_DS1.pdf
• File Type:
  [PDF - 440.20 KB ]