Background:
The public health benefit of suppressive antiviral therapy for reducing the risk of HSV-2 transmission to sex partners may be enhanced if persons at high risk for transmission can be identified.

Objective:
To determine whether clinical severity of genital herpes is associated with increased risk of HSV-2 transmission.

Method:
Analysis of history of genital herpes, observed rate of recurrences and shedding frequency (subset) among participants in a randomized controlled trial of daily valacyclovir 500 mg qd vs. placebo. Overall, 1,484 monogamous HSV-2 serodiscordant couples participated and 41 HSV-2 transmissions occurred during the 8 month trial.

Result:
The mean annual rate of recurrences prior to study entry did not differ between source partners who transmitted and those who did not, 4.8 vs. 5.1 respectively. The mean annualized frequency of reported recurrences during the study also did not differ among those who transmitted vs. those who did not for placebo recipients (4.4 vs. 4.8) or valacyclovir recipients (1.4 vs. 1.3). Among the 41 source partners who transmitted HSV-2, 8 of 27 placebo recipients and 7 of 14 valacyclovir recipients had no recurrences during the study. In the subset of 89 participants who obtained daily swabs for HSV DNA PCR, the shedding rate did not correlate with rate of recurrences prior to study entry (r=0.03; p=0.77) but did correlate with observed rate of recurrences during the study (r=0.43; p<0.001).

Conclusion:
Clinical assessment of HSV-2 disease severity is a poor predictor of the risk of transmission to sexual partners. HSV-2 transmission to sexual partners was not associated with reported history of frequent recurrences of genital herpes.

Implications:
Though individuals with frequent recurrences are most likely to benefit clinically from suppressive therapy, clinical history of genital herpes is not helpful in identifying targets who are most likely to transmit HSV-2.