Synergistic Antiviral Effects of Acyclovir and Vidarabine on Herpes simplex Infection in Newborn Mice

Abstract

277 5–7-day-old white Swiss mice were infected intranasally with Herpes simplex virus type 2 (HSV2) to mimic disseminated herpetic infection in human newborns. The antiviral efficacy of acyclovir, vidarabine and specific antiserum (SAS) alone and in combination was assessed. A significant increase in survival rate (52%) was observed with the combination of acyclovir (80 mg/kg/day) and vidarabine (125 mg/ kg/day) compared to either compound (24 and 6%, respectively) when therapy was begun 30 h after infection and continued daily for the next 4 days. Combinations of acyclovir, vidarabine and SAS had less protective effect (8%) than acyclovir with SAS (32%) or vidarabine with SAS (12%). No improvement was observed in survival rate of HSV2-infected mice treated with SAS as compared with controls (0% and 5%, respectively). These results suggest the enhanced antiherpes effect in newborn mice is due to synergism of acyclovir and vidarabine, a combination deserving further evaluation for the treatment of HSV2 infections in humans.

Delayed treatment with combinations of antiviral drugs in mice infected with herpes simplex virus and application of the median effect method of analysis

“…Several reports have demonstrated additive to synergistic effects with various combinations of ACV, ara-A, FIAC, and FMAU when treatment of HSV-infected mice was initiated within 48 h after virus inoculation (7,13,17,22,23; M. R. Karim, S. Bearney, D. E. Foster, C. Lopez, and K. A. Watanabe, Annu. Meet.…”