April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Very High Oral Doses of Valacyclovir Significantly Inhibit HSV-1 DNA Shedding into Tears and Saliva of Herpes Simplex Virus Type-1 Latent Rabbits
Author Affiliations & Notes
  • James M. Hill
    Ophthalmology,
    LSUHSC, New Orleans, Louisiana
  • Christian Clement
    Ophthalmology,
    LSUHSC, New Orleans, Louisiana
  • Harris E. McFerrin, Jr.
    Biology, Xavier University of Louisiana, New Orleans, Louisiana
  • Jeffery A. Hobden
    Microbiology, Immunology, Parasitology,
    LSUHSC, New Orleans, Louisiana
  • Timothy P. Foster
    Microbiology, Immunology, Parasitology,
    LSUHSC, New Orleans, Louisiana
  • Vaibhav Tiwari
    The College of Osteopathic Medicine, Pomona, California
  • Partha S. Bhattacharjee
    Biology, Xavier University of Louisiana, New Orleans, Louisiana
  • Hilary W. Thompson
    Biostatistics, School of Public Health,
    LSUHSC, New Orleans, Louisiana
  • Footnotes
    Commercial Relationships  James M. Hill, None; Christian Clement, None; Harris E. McFerrin, Jr., None; Jeffery A. Hobden, None; Timothy P. Foster, None; Vaibhav Tiwari, None; Partha S. Bhattacharjee, None; Hilary W. Thompson, None
  • Footnotes
    Support  NIH Grants EY006311, EY019144, EY02377; Research to Prevent Blindness; Louisiana Lions Eye Foundation; Lions International; South Louisiana Institute for Infectious Disease Research
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3261. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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