Genital-systemic chemokine gradients and the risk of HIV acquisition in women

Lenine J.P. Liebenberg, Lindi Masson, Kelly B. Arnold, Lyle R. McKinnon, Lise Werner, Elizabeth Proctor, Derseree Archary, Leila E. Mansoor, Douglas A. Lauffenburger, Quarraisha Abdool Karim, Salim S.Abdool Karim, Jo Ann S. Passmore

Research output: Contribution to journalArticle

14 Scopus citations

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-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 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-1b, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.

Original languageEnglish (US)
Pages (from-to)318-325
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume74
Issue number3
DOIs
StatePublished - Mar 1 2017

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)

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    Liebenberg, L. J. P., Masson, L., Arnold, K. B., McKinnon, L. R., Werner, L., Proctor, E., Archary, D., Mansoor, L. E., Lauffenburger, D. A., Karim, Q. A., Karim, S. S. A., & Passmore, J. A. S. (2017). Genital-systemic chemokine gradients and the risk of HIV acquisition in women. Journal of Acquired Immune Deficiency Syndromes, 74(3), 318-325. https://doi.org/10.1097/QAI.0000000000001218