HIV This Week

Foreskin inflammation is associated with HIV and herpes simplex virus type-2 infections in Rakai, Uganda.

Johnson KE, Sherman ME, Ssempiija V, Tobian AA, Zenilman JM, Duggan MA, Kigozi G, Serwadda D, Wawer MJ, Quinn TC, Rabkin CS, Gray RH. AIDS. 2009; 23:1807-15

Johnson and colleagues assessed foreskin inflammation associated with HIV and herpes simplex virus type 2 (HSV-2) in circumcised men. Foreskin tissues were assessed in 97 HIV-infected and 135 HIV-uninfected men enrolled in randomized trials of circumcision in Rakai, Uganda. Inflammation was quantified using an ordinal score evaluating extent, intensity, and cellular composition of infiltrates in the epithelium and stroma. Prevalence rate ratios of inflammation were estimated by multivariate Poisson regression. Foreskin inflammation was primarily focal. Epithelial inflammation was present in 4.2% of men with neither HIV nor HSV-2 infection; 7.8% of men with only HSV-2; 19.0% with HIV alone (P = 0.04); and 31.6% in HIV/HSV-2 coinfected men [prevalence rate ratio (PRR) 7.5, 95% confidence interval (CI) 2.3-23.8, P < 0.001]. Stromal inflammation was present in 14.1% of HIV/HSV-2 uninfected men, compared with 29.7% in men with HSV-2 alone (P = 0.03), 33.3% in men with HIV alone (P = 0.04), and 61.0% in men with HIV/HSV-2 coinfection (PRR 4.3, 95% CI 2.3-7.9, P < 0.001). In HIV-infected men, epithelial inflammation was associated with higher HIV viral load. Epithelial inflammation was more frequent among men reporting recent genital ulceration. Both epithelial and stromal inflammation were more common among men with smegma on physical examination. Foreskin inflammation is increased with HIV and HSV-2 infections, higher HIV viral load and presence of smegma. Foreskin inflammation may have implications for HIV transmission and acquisition in uncircumcised men.

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Editors’ note: This analysis of foreskins removed at medical circumcision supports the idea that local mucosal inflammation and ulcerative lesions, as well as recruitment of lymphocytes that target HIV to genital tissues, can influence HIV susceptibility and infectivity. Causative links cannot be made because this is a cross-sectional study but the highest prevalence of foreskin inflammation (in the epithelium and in the layer below it), was found in men with HIV/HSV-2 co-infection. Inflammation was also associated with smegma, a possible surrogate marker of poor genital hygiene. Since smegma could be the result of local inflammation or it be contributing to it, further research is warranted.