Neonatal herpes simplex virus (HSV) infection occurs in 1:3,000 to 1:20,000 live births, with 3 different phenotypes of illness: skin, eye, and mucous membranes (SEM), central nervous system (CNS) disease (meningoencephalitis), and disseminated disease affecting multiple organs. IV acyclovir (ACV) was approved by the Food and Drug Administration (FDA) in 1998 for neonatal HSV treatment; the initial dosing regimen, extrapolated from adult studies, was 30 mg/kg/d IV divided every 8 hours (standard dose, SD). Complications of HSV, however, remained unacceptably high: patients with disseminated disease had a mortality risk of ∼40% at 1 year of life, and up to 50% of survivors of HSV meningoencephalitis had significant morbidity subsequently.

To assess the safety and efficacy of higher doses of ACV in the treatment of neonatal HSV disease.

Phase 2 open-label prospective multicenter trial in the US and Mexico from 1989 to 1997.