Acyclovir versus vidarabine in herpes simplex encephalitis

Abstract

One hundred and twenty-seven patients with suspected herpes simplex encephalitis were entered in a randomised, controlled comparative study of therapy with acyclovir 10 mg/kg, 8-hourly, versus vidarabine, 15 mg/kg daily, for 10 days. Consecutive patients were included and nearly all diagnosed cases of HSV-encephalitis in Sweden were enrolled in the study. The diagnosis of HSV-encephalitis was verified by demonstration of intrathecal herpes simplex virus (HSV) antibody production and by HSV cultivation, or antigen detection, in brain biopsy or necropsy material. Of 53 confirmed cases of HSV-encephalitis (corresponding to 2.3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for therapeutic efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 12 month of observation 15 of 27 (56%) acyclovir recipients had no, or mild, sequelae compared with 3 of 24 (13%) vidarabine recipients (p = 0.002). Nineteen of 24 (79%) vidarabine-treated patients died or suffered severe sequelae, compared with 9 of 27 (33%) acyclovir-treated patients (p = 0.005). The effect of treatment was influenced by the level of consciousness at the start of therapy. The outcome for 20 vidarabine-treated patients above 30 years of age with HSE was similar to that for the 53 patients reported by an American collaborative study.