Self-reported behaviors and demographic factors were analyzed for association with HSV-1 or HSV-2 infection in the per-protocol cohort for months 2 through 20. Analysis of self-reported behavioral risk factors was restricted to 5980 sexually active subjects. An increased risk of HSV-1 infection was associated with 6 or more lifetime sexual partners (hazard ratio, 2.2; 95% CI, 1.3 to 3.8) and more than 1 partner in the previous 12 months (hazard ratio, 1.9; 95% CI, 1.4 to 2.7). Subjects who were 23 years of age or older were less likely to acquire HSV-1 than 18-to-22-year-olds (hazard ratio for subjects 23 to 26 years of age, 0.6; 95% CI, 0.4 to 0.8; hazard ratio for subjects 27 to 30 years of age, 0.4; 95% CI, 0.3 to 0.8). Factors not associated with an increased risk of HSV-1 infection included race or ethnic group, country of residence (United States or Canada), having a current partner with herpes, ever having a partner with herpes, condom use, history of any sexually transmitted infection (STI), and oral sex.

An increased risk of HSV-2 infection was associated with having 6 or more lifetime sexual partners (hazard ratio, 2.0; 95% CI, 1.1 to 3.8), having 6 or more partners in the previous 12 months (hazard ratio, 2.7; 95% CI, 1.3 to 5.5), ever having a partner with herpes (hazard ratio, 3.0; 95% CI, 1.7 to 5.3), having a current partner with herpes (hazard ratio, 3.4; 95% CI, 1.8 to 6.4), a history of any STI (hazard ratio, 3.3; 95% CI, 2.2 to 5.0), nonwhite race (hazard ratio, 3.1; 95% CI, 2.1 to 4.6), and U.S. residence (hazard ratio, 2.7; 95% CI, 1.2 to 6.2). Factors not associated with increased risk of HSV-2 infection included age, ethnic group, condom use, and oral sex. Initiation of sexual activity after 15 years of age was associated with a decreased risk of both HSV-1 infection (hazard ratio for initiation at 16 to 18 years of age, 0.6; 95% CI, 0.4 to 0.8; hazard ratio after 18 years of age, 0.3; 95% CI, 0.2 to 0.6) and HSV-2 infection (hazard ratio for initiation at 16 to 18 years of age, 0.5; 95% CI, 0.3 to 0.8; hazard ratio after 18 years of age, 0.3; 95% CI, 0.2 to 0.6).

Genital Shedding of HSV-2

Forty-three subjects (30 in the HSV-vaccine group and 13 in the control group) with HSV-2 infection collected anogenital swabs on 60 consecutive days, beginning 3 to 6 months after disease onset (15 subjects in the HSV-vaccine group and 9 in the control group) or seroconversion (15 subjects in the HSV-vaccine group and 4 in the control group). Analysis of these swabs showed that the rate of viral shedding was higher among the HSV-vaccine recipients than among controls (29% vs. 19%; relative risk, 1.55; 95% CI, 1.28 to 1.86). The mean quantity of HSV DNA on days with shedding did not differ between the two groups.