Innate Immune Activation Enhances Hiv Acquisition in Women, Diminishing the Effectiveness of Tenofovir Microbicide Gel

J Infect Dis. 2012 Oct 1;206(7):993-1001. doi: 10.1093/infdis/jis465. Epub 2012 Jul 24.

Abstract

The antiretroviral agent, tenofovir, formulated as a vaginal microbicide gel, reduces human immunodeficiency virus (HIV) acquisition by 39% in women. This study assessed the role of preexisting immune activation in HIV acquisition in women from the CAPRISA 004 trial, to identify potential strategies to increase the effectiveness of tenofovir gel. Systemic cytokine and cellular immune mediators (platelets and natural killer [NK] cells) were assessed in women at high risk for HIV assigned to either tenofovir or placebo gel in the CAPRISA 004 trial. Notwithstanding tenofovir gel use, women who acquired HIV had significantly higher systemic innate immune activation prior to infection than women who remained uninfected. Activation of both soluble (cytokine) and cellular (NK cells) immune mediators were associated with HIV acquisition, individually or in combination. Hence, an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides.

Publication types

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

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Avian Proteins / blood
  • Case-Control Studies
  • Coinfection
  • Cytokines / blood
  • Disease Susceptibility / blood
  • Disease Susceptibility / immunology
  • Female
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • Herpes Genitalis / immunology
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / immunology
  • Humans
  • Immunity, Innate*
  • Logistic Models
  • Lymphocyte Activation
  • Organophosphonates / therapeutic use*
  • Platelet Count
  • Principal Component Analysis
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Tenofovir
  • Vaginal Creams, Foams, and Jellies / therapeutic use*
  • Young Adult

Substances

  • Anti-HIV Agents
  • Avian Proteins
  • Cytokines
  • EMF-1 protein, Gallus gallus
  • Organophosphonates
  • Vaginal Creams, Foams, and Jellies
  • Tenofovir
  • Adenine