To determine the effect of antiviral agents in the treatment of HSV encephalitis on mortality and neurological sequelae at approximately two years. The secondary objective was to assess the adverse effect of antiviral agents on the patients.

Herpes simplex virus (HSV) infection of the brain is treated with antiviral drugs like Acyclovir. A summary of randomized control trials of antiviral drugs against HSV encephalitis has not been put forward yet.

Trials were identified by searching the PUBMED, European Medical Agency, USFDA, US Clinical trials, Elsevier database and Cochrane website and the reference lists of published trials.

A total of 5 studies met the criteria. The first study was published in 1980 and the latest was in 2015. All the studies used acyclovir/valacyclovir or vidarabine. Three studies compared acyclovir and vidarabine, one study was placebo controlled vidarabine trial and another one was a placebo controlled trial of long term valacyclovir therapy.

 Acyclovir improved mortality and lowered the incidence of neurological sequelae. There was no significant reduction in the risk of mortality with vidarabine therapy.

Trial evidence suggests that acyclovir decreases mortality and morbidity in acute HSV encephalitis.