Genital-systemic chemokine gradients and risk of HIV in women

28 February 2017

Research by the CAPRISA     Mucosal Immunology research team was recently published in JAIDS. The study shows that mucosa-biased gradients of IP-10, macrophage inflammatory protein–1b, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.

     Understanding host predictors of HIV risk has important implications for risk profiling and design of better HIV prevention methods. Mucosal and systemic immune mediators have been independently associated with HIV acquisition risk, but the relationship between compartments remains unclear.

     In this study 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.

     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 CVL 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–1b (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 (figure) confirmed this association, with gradients of IP-10, IL-8, and granulocyte-macrophage colony-stimulating factor concentrations correctly classifying 77% of HIV outcomes.

     These data underscore the importance of chemokines as determinants of HIV acquisition. Further studies to validate these findings could provide critical biomarkers for HIV risk profiling, allowing accurate classification of risk to implement more targeted HIV prevention strategies or conduct more rapid efficacy assessments of HIV prevention candidates. Translation of these findings through safe and effective manipulation of chemokine gradients, or by limiting their production or effects, could represent a novel and targeted host-directed HIV prevention modality.

For more information see:

Liebenberg LJ, et al. Genital – Systemic chemokine gradients and the risk of HIV acquisition in women. J AIDS 2017;74:318–325.