Acyclovir has been widely used as an effective and well-tolerated drug for the treatment of recurrent genital herpes simplex virus infection. Early initiation of treatment has been shown to reduce duration of viral shedding, time until healing and time until clearance of lesions. Since acyclovir is administered five times a day for five days, valacyclovir has been proposed as an alternative therapeutic agent. Tyring and associates compared the effectiveness of the two drugs in the treatment of recurrent genital herpes infections.

The double-blind, randomized study included 1,200 immunocompetent patients with recurrent genital herpes. Study subjects underwent therapy with oral valacyclovir, 1,000 mg twice daily; oral acyclovir, 200 mg five times daily, or placebo.

Both valacyclovir and acyclovir significantly decreased the length of the genital herpes episode compared with placebo. The episode resolved in approximately 75 percent of patients within six days of active drug therapy compared with eight days for placebo. Patients who initiated treatment within six hours after the prodrome experienced resolution 11 percent more quickly than those who started therapy after 24 hours. Both active drugs significantly reduced the time until lesion healing compared with placebo. Median healing times were 4.8 days for both active drugs, compared with 6.0 days for placebo. Healing time was faster in younger patients. At least one culture for herpes simplex virus was obtained from approximately 90 percent of the patients in each treatment group. Culture results were negative in 49 percent of the active drug groups, compared with 29 percent in the placebo group. The duration of viral shedding was significantly longer in the placebo group. Both active drugs significantly decreased the duration of pain compared with placebo. On the third day of treatment, only 12 to 15 percent of patients in the active drug groups reported moderate or severe pain, compared with 25 percent of patients receiving placebo. Adverse events were similar in all study groups, with headache, nausea and diarrhea occurring most frequently.

The authors conclude that treatment of recurrent herpes infections with a twice-daily regimen of valacyclovir or a five-times–daily regimen of acyclovir is significantly more effective than placebo in decreasing pain, and shortening the overall length of an episode and the period of viral shedding, with no significant differences between the two regimens. Because of the more convenient dosing schedule and the potential for improvement in compliance, valacyclovir is a useful alternative to acyclovir.