Rachel Heslop, Helen Roberts, Deralie Flower, Vanessa Jordan

Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode. To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases. We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection. All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators. 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; I(2) = 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, I(2) 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.