Effect of High versus Low Oral Doses of Valacyclovir on Herpes Simplex Virus-1 DNA Shedding into Tears of Latently Infected Rabbits

Abstract

To assess the effect of high doses of valacyclovir (VCV) on HSV-1 DNA shedding into tears of latently infected rabbits. Three oral doses of VCV were tested. Corneas were inoculated with HSV-1, and latent infection was allowed to establish. Starting on postinoculation (PI) day 28, tear swabs were collected once daily for 6 consecutive days before treatment. The rabbits were placed in five balanced groups: group 1 had no treatment, group 2 received placebo, group 3 received 7 mg/kg VCV, group 4 received 70 mg/kg, and group 5 received 140 mg/kg. The treatment was administered by oral gavage twice daily, starting on PI day 36 and continuing for 14 days. The ocular swabs were collected beginning on PI day 40 and continuing for 10 days. The mean copy number of HSV-1 DNA before treatment was 370+/-70, 569+/-273, 368+/-86, 408+/-108, and 396+/-91, and the mean HSV-1 DNA copy number after treatment was 232+/-183, 564+/-186, 518+/-122, 67+/-63, and 13+/-7 in groups 1 to 5, respectively. There was no observable toxicity in any group. The 70- and 140-mg/kg doses of VCV significantly reduced the HSV-1 DNA copy number, compared with that of the other three groups. A daily dose of 500 mg (approximately 7 mg/kg) VCV in healthy human volunteers did not suppress HSV-1 DNA shedding in tears and saliva. Thus, higher doses of VCV may be necessary to reduce asymptomatic shedding in healthy human subjects.