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James M. Hill, Christian Clement, Harris E. McFerrin, Jr., Jeffery A. Hobden, Timothy P. Foster, Vaibhav Tiwari, Partha S. Bhattacharjee, Hilary W. Thompson; Very High Oral Doses of Valacyclovir Significantly Inhibit HSV-1 DNA Shedding into Tears and Saliva of Herpes Simplex Virus Type-1 Latent Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3261.
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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.
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.
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.
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.
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