Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and acquisition: a nested case-control study among HIV-1-serodiscordant couples

J Infect Dis. 2015 May 1;211(9):1451-60. doi: 10.1093/infdis/jiu621. Epub 2014 Nov 10.


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.

Keywords: Africa; HIV-1 acquisition; immune activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa South of the Sahara / epidemiology
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • HIV Infections / blood
  • HIV Infections / epidemiology
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1*
  • Humans
  • Male
  • Risk Factors
  • Sexual Partners*
  • Young Adult


  • Cytokines