Genital-Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women

J Acquir Immune Defic Syndr. 2017 Mar 1;74(3):318-325. doi: 10.1097/QAI.0000000000001218.

Abstract

Background: Mucosal and systemic immune mediators have been independently associated with HIV acquisition risk, but the relationship between compartments remains unclear.

Methods: To address this, the concentrations of 12 cytokines were compared in matched plasma and cervicovaginal lavages (CVLs) from 57 HIV-positive women before their acquisition of HIV (cases) and 50 women who remained uninfected (controls) during the CAPRISA 004 trial.

Results: Although genital IP-10 concentrations were significantly higher in cases, plasma IP-10 concentrations were inversely associated with HIV risk. Comparing differences in mucosal and systemic cytokine concentrations between cases and controls, mucosa-biased gradients indicating higher cervicovaginal lavage relative to plasma concentrations were observed for all 5 chemokines in the panel. Four were significantly associated with HIV acquisition, including IP-10 (odds ratio [OR] 1.73, 95% confidence interval [CI]: 1.27 to 2.36), macrophage inflammatory protein-1β (OR 1.72, 95% CI: 1.23 to 2.40), interleukin (IL)-8 (OR 1.50, 95% CI: 1.09 to 2.05), and monocyte chemotactic protein-1 (OR 1.36, 95% CI: 1.01 to 1.83). None of the other 7 cytokines tested predicted HIV risk. Decision tree analyses confirmed this association, with gradients of IP-10, IL-8, and granulocyte-macrophage colony-stimulating factor concentrations correctly classifying 77% of HIV outcomes.

Conclusions: Our findings suggest that mucosa-biased gradients of IP-10, macrophage inflammatory protein-1β, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.

MeSH terms

  • Adult
  • Chemokines / analysis*
  • Female
  • Genitalia, Female / immunology*
  • HIV Infections / epidemiology*
  • Humans
  • Immunity, Mucosal*
  • Risk Assessment
  • Young Adult

Substances

  • Chemokines