The association of human immunodeficiency virus (HIV) acquisition with herpes simplex virus type 2 (HSV-2) was assessed among men who have sex with men (MSM) in a nested case-control study of 116 case subjects who seroconverted to HIV during follow-up and 342 control subjects who remained HIV seronegative, frequency-matched by follow-up duration and report of HIV-infected sex partner and unprotected anal sex. The baseline HSV-2 seroprevalence was higher among case (46%) than control (34%)

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... ts ( ); the HSV-2 P p .03 seroincidence was 7% versus 4% ( ). Only 15% of HSV-2-infected MSM reported herpes outbreaks in P p .3 the past year. HIV acquisition was associated with prior HSV-2 infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.9), reporting 112 sex partners (OR, 2.9; 95% CI, 1.4-6.3), and reporting fewer herpes outbreaks in the past year (OR, 0.3; 95% CI, 0.1-0.8). HSV-2 increases the risk of HIV acquisition, independent of recognized herpes lesions and behaviors reflecting potential HIV exposure. HSV-2 suppression with antiviral therapy should be evaluated as an HIV prevention strategy among MSM. Human immunodeficiency virus (HIV) prevalence and incidence in the United States is highest among men who have sex with men (MSM). Thus, the most effective prevention strategies should be directed toward