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Erin M. Kahle, for the Partners in Prevention HSV/HIV Transmission Study Team, Michael Bolton, for the Partners in Prevention HSV/HIV Transmission Study Team, James P. Hughes, for the Partners in Prevention HSV/HIV Transmission Study Team, Deborah Donnell, for the Partners in Prevention HSV/HIV Transmission Study Team, Connie Celum, for the Partners in Prevention HSV/HIV Transmission Study Team, Jairam R. Lingappa, for the Partners in Prevention HSV/HIV Transmission Study Team, Allan Ronald, for the Partners in Prevention HSV/HIV Transmission Study Team, Craig R. Cohen, for the Partners in Prevention HSV/HIV Transmission Study Team, Guy de Bruyn, for the Partners in Prevention HSV/HIV Transmission Study Team, Youyi Fong, for the Partners in Prevention HSV/HIV Transmission Study Team, Elly Katabira, for the Partners in Prevention HSV/HIV Transmission Study Team, M. Juliana McElrath, for the Partners in Prevention HSV/HIV Transmission Study Team, Jared M. Baeten, for the Partners in Prevention HSV/HIV Transmission Study Team, for the Partners in Prevention HSV/HIV Transmission Study Team, Connie Celum, Anna Wald, Jairam Lingappa, Amalia Magaret, James P. Hughes, Lawrence Corey, Jared M. Baeten, M. Juliana McElrath, David Coetzee, Kenneth Fife, Edwin Were, Max Essex, Joseph Makhema, Elly Katabira, Allan Ronald, Elizabeth Bukusi, Craig Cohen, Susan Allen, William Kanweka, Saidi Kapiga, Rachel Manongi, Carey Farquhar, Grace John-Stewart, James Kiarie, Susan Allen, Mubiana Inambao, Orange Farm, Sinead Delany-Moretlwe, Helen Rees, Guy de Bruyn, Glenda Gray, James McIntyre, Nelly Rwamba Mugo, Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples, The Journal of Infectious Diseases, Volume 211, Issue 9, 1 May 2015, Pages 1451–1460, https://doi.org/10.1093/infdis/jiu621
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Abstract
Background. A heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission – both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.
Methods. Using prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1–susceptible and HIV-1–infected partners. Plasma was collected before seroconversion for cases.
Results. For both HIV-1–infected and HIV-1–susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T2 test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1–susceptible and HIV-1–infected case partners, compared with HIV-1–susceptible and HIV-1–infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1–susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1–infected partners (P = .02).
Conclusions. Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.
