Effect of intensive acyclovir therapy during artificial reactivation of latent herpes simplex virus

The chemotherapeutic effect of intensive acyclovir (ACV) treatment was evaluated in New Zealand white rabbits with confirmed latent herpes simplex virus type 1 (HSV-1). Acyclovir was administered orally (1 mg/ml of drinking water), topically (three times per day), and intramuscularly (16.5 mg/kg body wt twice per day) beginning 36 days after ocular inoculation and continued for 4 consecutive weeks, during which time the rabbits underwent concurrent stimulation by bilateral iontophoresis of 0.01% epinephrine into the cornea to induce reactivation of latent virus. None of the eight rabbits receiving intensive ACV shed virus in their tear film sample during 4 weeks of concurrent epinephrine iontophoresis and antiviral therapy. All five rabbits receiving placebo treatment shed HSV in tear film samples. The total number of positive ocular samples was 14 during the first week of dual treatment (5/5 animals positive) and decreased to 2 positive samples (2/5 animals) during the fourth week of dual treatment. Upon sacrifice, HSV was isolated from 8 of 16 trigeminal ganglia of ACV-treated animals and 6 of 10 placebo-treated animals. No increased resistance to ACV was detectable in any of the virus isolated from trigeminal ganglia. Antibody and cellular immune responses were not significantly different between the ACV-treated and placebo-treated groups.