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American Journal of Epidemiology Advance Access originally published online on August 8, 2006
American Journal of Epidemiology 2006 164(8):733-741; doi:10.1093/aje/kwj270
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

High Risk of Human Immunodeficiency Virus in Men Who Have Sex with Men with Herpes Simplex Virus Type 2 in the EXPLORE Study

E. L. Brown1, A. Wald1,2,3, J. P. Hughes4, R. A. Morrow3,5, E. Krantz3, K. Mayer6,7, S. Buchbinder8, B. Koblin9 and C. Celum1,2

1 Department of Epidemiology, University of Washington, Seattle, WA
2 Department of Medicine, University of Washington, Seattle, WA
3 Department of Laboratory Medicine, University of Washington, Seattle, WA
4 Department of Biostatistics, University of Washington, Seattle, WA
5 Children's Hospital and Regional Medical Center, Seattle, WA
6 Department of Medicine, Brown University, Providence, RI
7 Fenway Community Health, Boston, MA
8 San Francisco Department of Public Health, San Francisco, CA
9 New York Blood Center, New York, NY

Correspondence to Dr. Connie Celum, Cabrini Medical Tower, 901 Boren Avenue, no. 1600, Seattle, WA 98104 (e-mail: ccelum{at}u.washington.edu).

The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioral intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003. Sexual behavior data were obtained by computer-assisted self-interview, and sera were collected semiannually for HIV and HSV-2 serology. HSV-2 infection was classified as "recent incident" (at the first HSV-2 seropositive visit), "remote incident" (within 24 months of the first positive visit), and "prevalent" (for visits >24 months after the first HSV-2 positive visit). Baseline HSV-2 prevalence was 20.3%. HSV-2 incidence was 1.9 (95% confidence interval (CI): 1.6, 2.2) per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months. The behavioral intervention did not reduce HSV-2 acquisition (adjusted hazard ratio (HR) = 1.2, 95% CI: 0.9, 1.6). Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years. HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants. HIV intervention strategies targeting HSV-2 prevention and suppression among men who have sex with men should be evaluated.

behavior therapy; herpes genitalis; herpesvirus 2, human; HIV; homosexuality, male


Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus; HR, hazard ratio; HSV-1, herpes simplex virus type 1; HSV-2, herpes simplex virus type 2


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