Data sources: The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Medline and Embase databases were searched together with the reference lists of primary studies, commentaries and reviews. Grey literature resources including the System for Information on Grey Literature in Europe, the Scopus Web and Patent searches, Proquest Dissertations and Theses Fulltext, the Index to Scientific and Technical Proceedings and the clinical trials registry (http://clinicaltrials.gov) were also searched.
Study selection: Randomised controlled trials (RCTs) involving nucleoside antiviral agents for the prevention of recurrent oral herpes in healthy immunocompetent subjects ≥12 years old were included. No language restrictions were applied. Study quality was assessed following Cochrane guidelines.
Data extraction and synthesis: Data were abstracted using a standardised data extraction form and analysed with meta-analysis carried out only with studies that reported the same outcome measure.
Results: Ten studies were included, only one study was considered to have a low risk of bias, five an unclear risk and four a high risk of bias. Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for four months) were shown to be effective in the prevention of RHL when taken prior to the appearance of any symptoms or exposure to triggers.
Conclusions: This review found support for the use of systemic acyclovir and valacyclovir for the prevention of RHL. However, the findings from this review should be interpreted with caution, because the methodologic assessment of the quality of the included studies showed an unclear risk of bias in five out of the ten included papers, and a high risk of bias in four studies.