Foreskin inflammation is associated with HIV and herpes simplex virus type-2 infections in Rakai, Uganda.
METHODS
We assessed foreskin inflammation associated with HIV and herpes simplex virus type 2 (HSV-2) in circumcised men.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Johnson
Kristine E
KE
Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, USA.
Sherman
Mark E
ME
Ssempiija
Victor
V
Tobian
Aaron A R
AA
Zenilman
Jonathan M
JM
Duggan
Maire A
MA
Kigozi
Godfrey
G
Serwadda
David
D
Wawer
Maria J
MJ
Quinn
Thomas C
TC
Rabkin
Charles S
CS
Gray
Ronald H
RH
D000293:Adolescent; D000328:Adult; D001446:Balanitis / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D002944:Circumcision, Male; D052816:Foreskin / Q000473:pathology*; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000150:complications* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012747:Sexual Partners; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D055815:Young Adult