Very High Oral Doses of Valacyclovir Significantly Inhibit HSV-1 DNA Shedding into Tears and Saliva of Herpes Simplex Virus Type-1 Latent Rabbits

Abstract

Purpose: : In a previous double-blind placebo-controlled clinical trial, the antiviral valacyclovir (7 mg/kg) alone or with aspirin (350 mg) did not reduce herpes simplex virus type 1 (HSV-1) DNA shedding into tears from normal healthy adults (IOVS 50:5601, 2009). High oral doses of valacyclovir (≤ 140 mg/kg) can reduce but not completely block viral shedding into tears of rabbits latently infected with a high phenotypic reactivator strain (McKrae) of HSV-1 (IOVS 51:4700, 2010). In this study, very high oral doses of valacyclovir (250 mg/kg) were administered to HSV-1 latent rabbits to determine if this dose would completely block viral shedding into tears and saliva. Drug treatment was twice daily for 11 consecutive days.

Methods: : This study employed a crossover experimental paradigm with balanced groups based on spontaneous shedding of HSV-1 DNA in the initial non-treated time. The experimental design had a five-day washout before the crossover. Viral shedding in tears and saliva of HSV-1 latent rabbits was quantified by a real-time PCR.

Results: : Valacyclovir at 250 mg/kg twice daily significantly reduced the number of shedders from 90-100% to 10-20%. Samples positive for HSV-1 DNA were detected in only the first five days of drug treatment. The last six days had no detection of HSV-1 DNA in tears or saliva. The average copy number of HSV-1 DNA in the untreated or vehicle-treated groups for both tear and saliva samples was 375. For the groups treated with valacyclovir, the average copy number was 15.

Conclusions: : This was the first study of detection and quantification of HSV-1 DNA in saliva of HSV-1 latent rabbits. We conclude that the high dose of oral valacyclovir significantly blocked HSV-1 DNA shedding into the tears and saliva of HSV-1 latent rabbits. Very high oral doses of valacyclovir may be needed to significantly block and/or completely inhibit asymptomatic HSV-1 DNA shedding in healthy human adults.

Keywords: herpes simplex virus • antiviral drugs • retina: neurochemistry