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 [Abstract] 1 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.
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.
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