Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment, incomplete outcome data in half of the studies and selective reporting).
A Cochrane review included 26 studies with a total of 6 950 subjects, of which 54% were female. The mean number of recurrences per year was 11 (range 6.3 to 17.8). Duration of treatment was 2 to 12 months. In placebo-controlled trials, the risk of having at least one clinical recurrence was reduced with acyclovir (RR 0.48, 95% confidence interval (CI) 0.39 to 0.58; 9 parallel-group trials, n = 2049), valacyclovir (pooled RR 0.41, 95% CI 0.24 to 0.69; 4 trials, n = 1788), or famciclovir (pooled RR 0.57, 95% CI 0.50 to 0.64; 2 trials, n = 732). The six cross-over trials showed larger treatment effects on average than the parallel-group trials. We found evidence of a small-study effect for acyclovir placebo-controlled trials (adjusted pooled RR 0.61, 95% CI 0.49 to 0.75). In analyzing parallel-group trials by daily dose, no clear evidence was found of a dose-response relationship for any drug. summarizes the results of one non-systematic review (2 RCTs, 1861 people) and one subsequent RCT (n=1479) on valaciclovir. Valaciclovir increased the time to recurrence (HR 0.10, 95% CU 0.11 to 0.21) and improved health-related quality of life (p<0.05). One systematic review (2 RCTs, 830 people) found that famciclovir increased the time to recurrence (11 months with 250 mg twice daily, 8 months with 125 mg 3 times daily, 1.5 months with placebo), and increased freedom from recurrence (78% with 250 mg twice daily, 42% with placebo). Four RCTs found that aciclovir 400 mg twice daily reduced recurrences compared with placebo (freedom from recurrence at 1 year 44–50% vs 0–5% with placebo. 210 adults in one trial who completed 5 years of continuous medication with aciclovir 400 mg twice daily, 53–70% were free of recurrences each year."?>
In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir and was not significantly different from that seen with famciclovir as compared with valacyclovir.In head-to-head trials, the risk of having at least one recurrence was increased with valacyclovir rather than acyclovir and was not significantly different from that seen with famciclovir as compared with valacyclovir. A network meta-analysis of 16 parallel-arm trials revealed no statistically significant differences between drugs. Adverse events were poorly reported.