Poverty and InequalitySexual and Reproductive HealthFamily, Maternal & Child HealthMethodology

Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda

TitleChemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda
Publication TypeJournal Article
Year of Publication2016
AuthorsProdger, JL, Gray, RH, Shannon, B, Shahabi, K, Kong, X, Grabowski, K, Kigozi, G, Nalugoda, F, Serwadda, D, Wawer, MJ, Reynolds, SJ, Liu, CM, Tobian, AA, Kaul, R
JournalPLoS Pathog
Date PublishedNov
ISBN Number1553-7374 (Electronic)1553-7366 (Linking)
Accession Number27898732
Keywords*Circumcision, Male, Adolescent, Adult, Chemokines/analysis/*immunology, Disease Susceptibility/immunology/virology, Female, Foreskin/immunology, HIV Infections/*epidemiology/immunology/prevention & control, HIV-1, Humans, Immunohistochemistry, Inflammation/immunology/virology, Interleukin-8/immunology, Luminescent Measurements, Male, Middle Aged, Penis/*immunology/surgery, Uganda, Young Adult

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04-6.40) and Monokine Induced by gamma-interferon (MIG aOR 2.72, 95%CI 1.15-8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44-0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16-0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.