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 Delaney, W. E.
Right arrow Articles by Xiong, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delaney, W. E., IV
Right arrow Articles by Xiong, S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2004, p. 3702-3710, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3702-3710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Combinations of Adefovir with Nucleoside Analogs Produce Additive Antiviral Effects against Hepatitis B Virus In Vitro

William E. Delaney IV,* Huiling Yang, Michael D. Miller, Craig S. Gibbs, and Shelly Xiong

Gilead Sciences, Inc., Foster City, California

Received 6 February 2004/ Returned for modification 23 March 2004/ Accepted 8 June 2004

Combination therapies may be required for long-term management of some patients chronically infected with hepatitis B virus (HBV). Adefovir is a nucleotide analog that has similar activity against wild-type and lamivudine-resistant HBV. In contrast to lamivudine, clinical resistance to the prodrug adefovir dipivoxil emerges infrequently. Based on its clinical efficacy and low frequency of resistance, adefovir dipivoxil may form an important component of combination regimens. We therefore investigated the in vitro antiviral efficacy of combinations of adefovir with other nucleoside analogs (lamivudine, entecavir, emtricitabine [FTC],and telbivudine [L-dT]) and the nucleotide analog tenofovir. Using a novel stable cell line that expresses high levels of wild-type HBV, we assayed the antiviral activity of each drug alone and in combination with adefovir. All two-drug combinations resulted in greater antiviral effects than treatments with single agents and could be characterized as additive by the Bliss independence model. Analysis using the Loewe additivity model indicated that adefovir exerted additive antiviral effects when combined with lamivudine, FTC, or L-dT and moderately synergistic effects when combined with entecavir or tenofovir. There was no evidence of cytotoxicity with any of the drugs when used alone or in combination at the tested doses.

* Corresponding author. Mailing address: 333 Lakeside Dr., Foster City, CA 94402. Phone: (650) 522-5598. Fax: (650) 522-5890. E-mail: wdelaney{at}gilead.com.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3702-3710, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3702-3710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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]  
  • Dusheiko, G, Antonakopoulos, N (2008). Current treatment of hepatitis B. Gut 57: 105-124 [Full Text]  
  • Bifano, M., Yan, J.-H., Smith, R. A., Zhang, D., Grasela, D. M., LaCreta, F. (2007). Absence of a Pharmacokinetic Interaction Between Entecavir and Adefovir. J Clin Pharmacol 47: 1327-1334 [Abstract] [Full Text]  
  • Zhou, X.-J., Fielman, B. A., Lloyd, D. M., Chao, G. C., Brown, N. A. (2006). Pharmacokinetics of telbivudine in healthy subjects and absence of drug interaction with Lamivudine or adefovir dipivoxil.. Antimicrob. Agents Chemother. 50: 2309-2315 [Abstract] [Full Text]  
  • Kim, J. W, Park, S. H, Louie, S. G (2006). Telbivudine: A Novel Nucleoside Analog for Chronic Hepatitis B. The Annals of Pharmacotherapy 40: 472-478 [Abstract] [Full Text]  
  • Lim, S. G., Ng, T. M., Kung, N., Krastev, Z., Volfova, M., Husa, P., Lee, S. S., Chan, S., Shiffman, M. L., Washington, M. K., Rigney, A., Anderson, J., Mondou, E., Snow, A., Sorbel, J., Guan, R., Rousseau, F., for the Emtricitabine FTCB-301 Study Group, (2006). A Double-blind Placebo-Controlled Study of Emtricitabine in Chronic Hepatitis B. Arch Intern Med 166: 49-56 [Abstract] [Full Text]  
  • Zoulim, F. (2005). Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental models. J Antimicrob Chemother 55: 608-611 [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»