This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Menne, S. Articles by Tennant, B. C. Search for Related Content PubMed PubMed Citation Articles by Menne, S. Articles by Tennant, B. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2005, p. 2720-2728, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2720-2728.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antiviral Effect of Oral Administration of Tenofovir Disoproxil Fumarate in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853,¹ Division of Molecular Virology and Immunology, Department of Microbiology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850,² Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, California 94404³

Received 16 November 2004/ Returned for modification 28 January 2005/ Accepted 4 March 2005

Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue approved for treatment of human immunodeficiency virus (HIV) infection. TDF also has been shown in vitro to inhibit replication of wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants and to inhibit lamivudine-resistant HBV in patients and HBV in patients coinfected with the HIV. Data on the in vivo efficacy of TDF against wild-type virus in non-HIV-coinfected or lamivudine-naïve chronic HBV-infected patients are lacking in the published literature. The antiviral effect of oral administration of TDF against chronic woodchuck hepatitis virus (WHV) infection, an established and predictive animal model for antiviral therapy, was evaluated in a placebo-controlled, dose-ranging study (doses, 0.5 to 15.0 mg/kg of body weight/day). Four weeks of once-daily treatment with TDF doses of 0.5, 1.5, or 5.0 mg/kg/day reduced serum WHV viremia significantly (0.2 to 1.5 log reduction from pretreatment level). No effects on the levels of anti-WHV core and anti-WHV surface antibodies in serum or on the concentrations of WHV RNA or WHV antigens in the liver of treated woodchucks were observed. Individual TDF-treated woodchucks demonstrated transient declines in WHV surface antigen serum antigenemia and, characteristically, these woodchucks also had transient declines in serum WHV viremia, intrahepatic WHV replication, and hepatic expression of WHV antigens. No evidence of toxicity was observed in any of the TDF-treated woodchucks. Following drug withdrawal there was prompt recrudescence of WHV viremia to pretreatment levels. It was concluded that oral administration of TDF for 4 weeks was safe and effective in the woodchuck model of chronic HBV infection.

This article has been cited by other articles:

• Menne, S., Butler, S. D., George, A. L., Tochkov, I. A., Zhu, Y., Xiong, S., Gerin, J. L., Cote, P. J., Tennant, B. C. (2008). Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 52: 3617-3632 [Abstract] [Full Text]  
• Menne, S., Asif, G., Narayanasamy, J., Butler, S. D., George, A. L., Hurwitz, S. J., Schinazi, R. F., Chu, C. K., Cote, P. J., Gerin, J. L., Tennant, B. C. (2007). Antiviral Effect of Orally Administered ( )-{beta}-D-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 51: 3177-3184 [Abstract] [Full Text]  
• Delaney, W. E. IV, Ray, A. S., Yang, H., Qi, X., Xiong, S., Zhu, Y., Miller, M. D. (2006). Intracellular Metabolism and In Vitro Activity of Tenofovir against Hepatitis B Virus.. Antimicrob. Agents Chemother. 50: 2471-2477 [Abstract] [Full Text]