Enhanced efficacy of nucleoside analogs and recombinant alpha interferon in weanling mice lethally infected with herpes simplex virus type 2.
Weanling ICR Swiss mice were inoculated intranasally with a lethal dose of herpes simplex virus type 2, and treated with either vidarabine, vidarabine-5'-monophosphate, acyclovir or a hybrid recombinant human alpha interferon which is active in murine tissues. Treatment with antiviral drugs was initiated 2, 24, 48, 72 or 96 h following virus inoculation. Single drug treatment showed little effect on mortality, with only acyclovir showing some slight reduction. Four dual drug combinations (vidarabine/acyclovir; vidarabine/interferon; vidarabine 5'-monophosphate/acyclovir and vidarabine 5'-monophosphate/interferon) were all associated with marked reductions of mortality when treatment was begun at 2 h, and this beneficial effect increased further when therapy was delayed until 24 or 48 h following virus inoculation. However, the combination of acyclovir/interferon was consistently toxic to the mice, unless a reduction in dosages was employed. These results suggest that certain antiviral combinations might be useful for serious human infections caused by herpes simplex virus.
Crane
L R
LR
Department of Medicine, Wayne State University, Detroit, Michigan.
Sunstrum
J C
JC
D000212:Acyclovir / Q000008:administration & dosage*; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006561:Herpes Simplex / Q000188:drug therapy*; D007370:Interferon Type I / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014740:Vidarabine / Q000008:administration & dosage*; D001084:Vidarabine Phosphate / Q000008:administration & dosage
D007370:Interferon Type I; D001084:Vidarabine Phosphate; D014740:Vidarabine; D000212:Acyclovir