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

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2008, p. 3617-3632, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00654-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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 {triangledown}

Stephan Menne,1* Scott D. Butler,1 Andrea L. George,1 Ilia A. Tochkov,1 Yuao Zhu,2 Shelly Xiong,2 John L. Gerin,3 Paul J. Cote,3 and Bud C. Tennant1

Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853,1 Gilead Sciences, Inc., 4 University Place, 4611 University Drive, Durham, North Carolina 27707,2 Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 200573

Received 17 May 2008/ Returned for modification 1 July 2008/ Accepted 25 July 2008

Adefovir dipivoxil (ADV) and tenofovir disoproxil fumarate (TDF) are nucleotide analogs that inhibit the replication of wild-type hepatitis B virus (HBV) and lamivudine (3TC)-resistant virus in HBV-infected patients, including those who are coinfected with human immunodeficiency virus. The combination of ADV or TDF with other nucleoside analogs is a proposed strategy for managing antiviral drug resistance during the treatment of chronic HBV infection. The antiviral effect of oral ADV or TDF, alone or in combination with 3TC or emtricitabine (FTC), against chronic woodchuck hepatitis virus (WHV) infection was evaluated in a placebo-controlled study in the woodchuck, an established and predictive model for antiviral therapy. Once-daily treatment for 48 weeks with ADV plus 3TC or TDF plus FTC significantly reduced serum WHV viremia levels from the pretreatment level by 6.2 log10 and 6.1 log10 genome equivalents/ml serum, respectively, followed by TDF plus 3TC (5.6 log10 genome equivalents/ml), ADV alone (4.8 log10 genome equivalents/ml), ADV plus FTC (one survivor) (4.4 log10 genome equivalents/ml), TDF alone (2.9 log10 genome equivalents/ml), 3TC alone (2.7 log10 genome equivalents/ml), and FTC alone (2.0 log10 genome equivalents/ml). Individual woodchucks across all treatment groups also demonstrated pronounced declines in serum WHV surface antigen, characteristically accompanied by declines in hepatic WHV replication and the hepatic expression of WHV antigens. Most woodchucks had prompt recrudescence of WHV replication after drug withdrawal, but individual woodchucks across treatment groups had sustained effects. No signs of toxicity were observed for any of the drugs or drug combinations administered. In conclusion, the oral administration of 3TC, FTC, ADV, and TDF alone and in combination was safe and effective in the woodchuck model of HBV infection.

* Corresponding author. Mailing address: Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Room C-2005 VMC, Cornell University, Ithaca, NY 14853. Phone: (607) 253-3596. Fax: (607) 253-3289. E-mail: sm119{at}cornell.edu

{triangledown} Published ahead of print on 1 August 2008.

Antimicrobial Agents and Chemotherapy, October 2008, p. 3617-3632, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00654-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rodriguez-Madoz, J. R., Liu, K. H., Quetglas, J. I., Ruiz-Guillen, M., Otano, I., Crettaz, J., Butler, S. D., Bellezza, C. A., Dykes, N. L., Tennant, B. C., Prieto, J., Gonzalez-Aseguinolaza, G., Smerdou, C., Menne, S. (2009). Semliki Forest Virus Expressing Interleukin-12 Induces Antiviral and Antitumoral Responses in Woodchucks with Chronic Viral Hepatitis and Hepatocellular Carcinoma. J. Virol. 83: 12266-12278 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»