A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections

Objective: To compare valacyclovir hydrochloride with acyclovir in the treatment of recurrent genital herpes infection. Design: A multicenter, double-blind, placebo-controlled, randomized, parallel-design study. Setting: University clinics (dermatology, gynecology, and infectious diseases) and private practices. Patients: One thousand two hundred patients with recurrent genital herpes simplex infections. Interventions: Patients self-initiated oral therapy with 1000 mg of valacyclovir hydrochloride twice daily, 200 mg of acyclovir 5 times daily, or placebo for 5 days. Main Outcome Measures: Resolution of all signs and symptoms of recurrent genital herpes infection. Results: Both drugs were significantly more effective than placebo in speeding resolution of herpetic episodes (median duration, 4.8, 4.8, and 5.9 days, respectively); the hazards ratios for valacyclovir and acyclovir vs placebo were 1.66 (95% confidence interval [CI], 1.38-2.01) and 1.71 (95% CI, 1.41-2.06) (both P<.001). Similarly, valacyclovir and acyclovir significantly hastened lesion healing (hazards ratios vs placebo were 1.88 [95% CI, 1.53-2.32] and 1.90 [95% CI, 1.55-2.34], respectively; P<.001). Pain duration was shorter in valacyclovir- and acyclovir-treated patients (median, 2 vs 3 days). Viral shedding stopped 2.55 times faster in patients treated with valacyclovir and 2.24 times faster in patients treated with acyclovir than in patients treated with placebo; Aborted episodes, in which lesions did not progress beyond the macule or papule stage, tended to occur in more patients treated with valacyclovir (25.9%) or acyclovir (24.8%) than in patients treated with placebo (19.8%). Valacyclovir and acyclovir did not differ significantly with regard to their respective effects on any of the above efficacy-parameters. The nature, severity, and frequency of adverse events did not differ among the 3 treatment groups. Conclusions: Twice-daily valacyclovir was as effective and well tolerated in the treatment of recurrent genital herpes simplex virus infection as 5-times-daily acyclovir. Therefore, valacyclovir could prove a useful alternative to acyclovir when convenience of dosing or compliance issues are the prime considerations in treatment.