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Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples
- Kahle, Erin M;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Bolton, Michael;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Hughes, James P;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Donnell, Deborah;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Celum, Connie;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Lingappa, Jairam R;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Ronald, Allan;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Cohen, Craig R;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- de Bruyn, Guy;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Fong, Youyi;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Katabira, Elly;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- McElrath, M Juliana;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Baeten, Jared M;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Team, for the Partners in Prevention HSV HIV Transmission Study;
- Celum, Connie;
- Wald, Anna;
- Lingappa, Jairam;
- Magaret, Amalia;
- Hughes, James P;
- Corey, Lawrence;
- Baeten, Jared M;
- McElrath, M Juliana;
- Coetzee, David;
- Fife, Kenneth;
- Were, Edwin;
- Essex, Max;
- Makhema, Joseph;
- Katabira, Elly;
- Ronald, Allan;
- Bukusi, Elizabeth;
- Cohen, Craig;
- Allen, Susan;
- Kanweka, William;
- Kapiga, Saidi;
- Manongi, Rachel;
- Farquhar, Carey;
- John-Stewart, Grace;
- Kiarie, James;
- Allen, Susan;
- Inambao, Mubiana;
- Farm, Orange;
- Delany-Moretlwe, Sinead;
- Rees, Helen;
- de Bruyn, Guy;
- Gray, Glenda;
- McIntyre, James;
- Mugo, Nelly Rwamba
- et al.
Published Web Location
https://doi.org/10.1093/infdis/jiu621Abstract
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 T(2) 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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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