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

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

Author information

1
Department of Epidemiology.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
3
Department of Biostatistics.
4
Department of Epidemiology Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
5
Department of Epidemiology Department of Global Health Department of Medicine.
6
Department of Global Health Department of Medicine Department of Pediatrics, University of Washington.
7
Department of Medicine, University of Manitoba, Winnepeg, Canada.
8
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco.
9
Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.
10
Infectious Disease Institute, Makerere University, Kampala, Uganda.
11
Department of Global Health Department of Medicine Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.

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 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

PMID:
25389306
PMCID:
PMC4447828
DOI:
10.1093/infdis/jiu621
[Indexed for MEDLINE]
Free PMC Article

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