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*Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; †Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa; ‡Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa; §Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA; ‖Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI; ¶Department of Epidemiology, Columbia University, New York City, NY; and #National Health Laboratory Service, Johannesburg, South Africa.
Published: March 2017
AI Article Synopsis
Article 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.
