Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.