Gupta R, Wald A, Krantz E, Selke S, Warren T, Vargas-Cortes M et al. J Infect Dis 2004;190:1374–1381

BACKGROUND: Valacyclovir exhibits better oral absorption and higher, more prolonged serum concentrations than oral aciclovir. The efficacy of valacyclovir and aciclovir on genital herpes simplex virus (HSV) shedding was assessed in a double-blind, 3-period crossover trial.
METHODS: Sixty-nine immunocompetent participants with genital HSV-2 received oral valacyclovir, aciclovir, and matching placebo in random order for 7-week periods. Participants provided daily genital mucosal swabs for HSV detection by viral culture and polymerase chain reaction (PCR).
RESULTS: HSV was detected at least once in 62 (90%) participants by culture and in 68 (98%) by PCR. During placebo, the total HSV shedding rate was 15.4% of days by culture (PCR, 40.2%); the subclinical shedding rate was 6.6% by culture (PCR, 27.1%). Both antivirals were associated with lower HSV shedding by culture (relative risk [RR], 0.03 [95% confidence interval {CI}, 0.010.07] for valacyclovir and RR, 0.05 [95% CI, 0.030.10] for aciclovir) and PCR (RR, 0.18 [95% CI, 0.120.26] for valacyclovir and RR, 0.20 [95% CI, 0.150.28] for aciclovir), compared with placebo. No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and aciclovir arms.
CONCLUSIONS: Although the suppression of viral replication is not complete, valacyclovir and aciclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding.