This report is concerned with the capacities of aciclovir to protect mice challenged intracerebrally with multiple lethal doses of type 1 herpes simplex virus and to control multiplication of this virus in the brain. With treatment initiated 12 h after inoculation and continued for 4 consecutive days, aciclovir administered subcutaneously in daily doses ranging from 40 to 100 mg/kg led to 21-day survival rates of from 33 to 73% and reduced virus titers by 1 to 1,h x 4 logs on postchallenge day 8. The therapeutic accomplishments of the 100-mg/kg doses of aciclovir were comparable to those of 1,000-mg/kg doses of vidarabine (9-,B-Darabinofuranosyladenine); however, as measured by impact on body weight, aciclovir was better tolerated than vidarabine at these similarly effective doses.Aciclovir [ACV; 9-(2-hydroxyethoxymethyl)-guanine, or acycloguanosine] has been introduced recently as a potent and selective antiviral agent against herpes simplex virus type 1 (HSV-1) and 7,9,13,16). In vitro this compound also inhibits the multiplication ofvaricella zoster virus, cytomegalovirus, and B virus but has no effect on vaccinia virus, adenovirus type 5, and a range of ribonucleic acid viruses (16). ACV penetrates infected cells to a greater degree than uninfected cells (6). Once introduced into cells, it is converted to a monophosphate form by an HSV-specific thymidine kinase and eventually to a triphosphate form. ACV triphosphate then acts by inhibition of viral DNA polymerase. An additional selective advantage is that ACV triphosphate has a 30-foldgreater affinity for viral deoxyribonucleic acid polymerase than for cellular deoxyribonucleic acid polymerase in vitro (6,7). In the present study we evaluated the therapeutic efficacy of ACV for the herpes encephalitis by observing the capacities of ACV to protect mice inoculated intracerebrally with HSV-1 and to control the multiplication of this virus in the brain. More Forty-five mice inoculated with saline were divided into three equal subgroups which were treated as follows: (i) phosphate-buffered saline, 0.2 ml/day; (ii) ACV, 100 mg/kg per day; or (iii) ara-A, 1,000 mg/kg per day. Treatments were initiated 12 h after the inoculation of HSV-1 or saline and consisted of subcutaneous injections of two divided doses per day for 4 days. The mice were weighed on days 0, 2, 4, 8, 10, 14, and 16 after the inoculation to monitor weight change. The

The local and trigeminal ganglionic therapeutic efficacy of two topical and systemic antiviral drugs was studied in mouse lips inoculated with herpes simplex virus type 1 after thermal injury. Application of topical 3% acylovir (acycloguanosine) ointment three times daily for four days completely blocked the replication of virus in the lips, and the healing process was greatly accelerated compared with that in placebo-treated infected controls. However, neither the healing process nor the viral replication was influenced by similar therapy with 3% vidarabine ointment. When given systemically for four days, starting one day after inoculation, acyclovir (40-60 mg/kg per day) and vidarabine (50 mg/kg per day) significantly reduced the clinical manifestations on the lips and viral titers of cultures obtained from the lips. Establishment of viral latency in the trigeminal ganglion was significnatly inhibited by systemic acyclovir (60 mg/kg per day), whereas systemic vidarabine (50 mg/kg per day) was ineffective. These data suggest that acyclovir may be one of the most promising antiviral agents for the management of oral herpes viral infections and trigeminal ganglionic latency of virus as demonstrated in the mouse model.