Abstract: Six RCTs with a total of 1211 participants were eligible; five trials evaluated oral aciclovir, and one, with 419 participants, evaluated oral famciclovir. We were able to conduct meta-analyses as there were sufficient similarities in the included studies, such as the reporting of the presence of PHN, duration of rash before treatment initiation and treatment regimen. For our primary outcome, based on three trials (609 participants) we found no significant difference between the aciclovir and control groups in the incidence of PHN four months after the onset of the acute herpetic rash (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.51 to 1.11), nor was there a significant difference at six months (RR 1.05, 95% CI 0.87 to 1.27, two trials, 476 participants). In four of the trials (692 participants), there was some evidence for a reduction in the incidence of pain four weeks after the onset of rash. In the trial of famciclovir versus placebo, neither 500 mg nor 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly. The most commonly reported adverse events were nausea, vomiting, diarrhoea and headache for aciclovir, and headache and nausea for famciclovir. For neither treatment was the incidence of adverse events significantly different from placebo. None of the studies were at high risk of bias, although the risk of bias was unclear in at least one domain for all but one study. We found no new RCTs when we updated the searches in April 2013. There is high quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments; therefore, further well-designed RCTs are needed to investigate famciclovir or other new antiviral agents in preventing PHN. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different subgroups of people, such as people who are immunocompromised.

Plain-language summary: We identified six clinical trials that met our standards for inclusion in the review. They included a total of 1319 participants. We decided that our main measure of whether antiviral medicines work in preventing PHN would be whether or not PHN had developed six months after a first attack of shingles (some of the studies we included of aciclovir measured PHN at four months). Aciclovir, which is an antiviral medicine, was used in five trials (900 participants) and was not better than a placebo (dummy pill) in preventing PHN. In the other trial (419 participants), famciclovir, which is another antiviral drug, was no better than placebo in preventing pain following healing of the shingles rash. The number of side effects with aciclovir and famciclovir was not very different from the number with placebo. The trials did not have any major problems of design or conduct that put the results in doubt, although most of the reports did not provide enough information to fully assess every aspect. We conclude that according to high quality evidence, oral aciclovir was ineffective in reducing the incidence of PHN and there is not enough evidence on other antiviral treatments. There need to be further well-designed trials of famciclovir or other new antiviral agents with a greater number of participants. Future trials should pay more attention to the severity of pain and quality of life of participants, and should include different groups of people, such as those who have lowered immunity. The evidence is current to April 2013, when the searches were last updated. Because new evidence on this topic is slow to emerge, we have scheduled the next update of this review for 2017.