A randomized, double-blind, comparative trial comparing high- and standard-dose oral acyclovir for first-episode...

Orally administered acyclovir ameliorates the clinical course and decreases the duration of viral shedding in patients with first-episode genital herpes infections. We investigated in a randomized, double-blind, comparative trial whether a higher (4 g) than standard (1 g) daily dose of oral acyclovir results in greater clinical benefit and influences the time to first recurrence. A total of 139 patients with first-episode genital herpes were randomized to receive orally 4 or 1 g of acyclovir daily. A total of 52 subjects were excluded from the efficacy analysis because most had recurrent disease. Of 87 eligible subjects, 28 (32%) had primary herpes simplex virus type 1 (HSV-1) infections, 48 (55%) had primary HSV-2 infections, and 11 (13%) had nonprimary HSV-2 infections. We did not find any statistically significant differences in the duration of symptoms or viral shedding between the two dose groups, nor did the median time to first recurrence differ between the two groups. Initiation of therapy with either dose within the first 3 days of the appearance of symptoms shortened the duration of the first episode. Adverse gastrointestinal effects developed in 8% of subjects receiving the higher dose, whereas no adverse reactions were observed among those receiving the standard dose (P = 0.10). We conclude that, in comparison with standard therapy, higher-dose oral acyclovir does not result in additional clinical benefit or modify the time to first recurrence. The present study may have implications for the development and efficacy of congeners of acyclovir which provide higher levels in blood than the standard dose of acyclovir.