To evaluate the frequency of reactivation of genital herpes infection and to identify predictors for recurrence.

Prospective, observational cohort study.

Research clinic.

457 consecutive patients who did not have acute-phase serum antibodies to herpes simplex virus type 2 (HSV-2) but who did have herpes simplex virus (HSV) isolated from genital lesions.

Eighty-nine percent of patients with HSV-2 had at least one recurrence during follow-up (median, 391 days); the median monthly recurrence rate was 0.34. Thirty-eight percent had at least 6 recurrences during the first year and 20% had more than 10 recurrences. The median monthly recurrence rate was 0.43 for men and 0.33 for women (difference, 0.10 [95% CI, 0.03 to 0.19]; P < 0.01). Twenty-six percent of women and 8% of men had no or 1 recurrence in year 1 of follow-up, whereas 14% of women and 26% of men had more than 10 recurrences. Patients who had severe primary HSV-2 infection (duration, ≥ 35 days) had recurrences nearly twice as often (0.66 compared with 0.36 recurrences per month [95% CI, 0.18 to 0.57]) and had a shorter time to first recurrence when compared with those who had shorter first episodes.

Almost all persons with initially symptomatic HSV-2 infection have symptomatic recurrences. More than 35% of such patients have frequent recurrences. Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether they receive antiviral chemotherapy with acyclovir. Men with genital HSV-2 infection have about 20% more recurrences than do women, a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.