Abstract: We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I2 = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies. There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I2 statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes. Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo. There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse.

Plain-language summary: We included 26 randomised controlled trials (RCTs) trials with 2084 participants that looked at treatments for first-episode genital herpes versus placebo or another treatment. The trials all included people who were having their first episode of genital herpes and were conducted in various countries around the world. Three of the trials included only women, and in all the trials the participants had had symptoms for eight days or less. Fifteen of the 26 trials were funded by a pharmaceutical company.Key resultsThe evidence is current to April 2016. The evidence shows that oral and intravenous acyclovir may be effective in reducing the number of days of symptoms in someone with first-episode genital herpes. Oral valaciclovir showed a similar length of symptom duration as acyclovir. We did not find enough evidence to support the use of topical treatments. There was also no evidence that any of the treatments reduced the time between episodes for people with genital herpes. The evidence presented here is mostly of low quality. The studies included were mainly conducted in the 1980s and at this time the brief way studies were reported does not allow us to adequately judge the quality of the included studies.Quality of the evidenceThe evidence provided by this review is of low quality. Although there are 26 included studies, the meta-analyses created in this review at the most, had three included studies. This was mainly due to the low number of studies that looked at each different type of antiviral. It was also unclear as to how well the included studies were conducted, as the methods for each of the individual studies did not report enough detail to judge each study's quality, inconsistence and this also affected the overall quality of the review.