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

Johnson, Kristine Ea; Sherman, Mark Eb; Ssempiija, Victorc,d; Tobian, Aaron ARe; Zenilman, Jonathan Ma; Duggan, Maire Af; Kigozi, Godfreyc; Serwadda, Davidc,g; Wawer, Maria Jd; Quinn, Thomas Ca,h; Rabkin, Charles Sb; Gray, Ronald Hd,*

doi: 10.1097/QAD.0b013e32832efdf1
Basic Science

Design: 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.

Conclusion: 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.

Author Information

aDepartment of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, USA

bNational Cancer Institute, Rockville, Maryland, USA

cRakai Health Sciences Program, Kalisizo, Uganda

dDepartment of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, USA

eDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

fDepartment of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada

gSchool of Public Health, Makerere University, Kampala, Uganda

hDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

* Additional authors listed in acknowledgements section.

Received 3 February, 2009

Revised 28 May, 2009

Accepted 3 June, 2009

Correspondence to Kristine E. Johnson, MD, B-3N, 4940 Eastern Ave, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA. Tel: +1 410 550 8398; fax: +1 410 550 1169; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.