Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and acquisition: a nested case-control study among HIV-1-serodiscordant couples.
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.
Department of Epidemiology.
Erin M
EM
Kahle
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
Michael
M
Bolton
Department of Biostatistics.
James P
JP
Hughes
Department of Epidemiology Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
Deborah
D
Donnell
Department of Epidemiology Department of Global Health Department of Medicine.
Connie
C
Celum
Department of Global Health Department of Medicine Department of Pediatrics, University of Washington.
Jairam R
JR
Lingappa
Department of Medicine, University of Manitoba, Winnepeg, Canada.
Allan
A
Ronald
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco.
Craig R
CR
Cohen
Perinatal HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.
Guy
G
de Bruyn
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
Youyi
Y
Fong
Infectious Disease Institute, Makerere University, Kampala, Uganda.
Elly
E
Katabira
Department of Global Health Department of Medicine Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle.
M Juliana
MJ
McElrath
Department of Epidemiology Department of Global Health Department of Medicine.
Jared M
JM
Baeten
D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D012307:Risk Factors; D012747:Sexual Partners; D055815:Young Adult
D016207:Cytokines
Africa; HIV-1 acquisition; immune activation