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      Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro.

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          Abstract

          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.

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          Author and article information

          Journal
          Antimicrob. Agents Chemother.
          Antimicrobial agents and chemotherapy
          0066-4804
          0066-4804
          Oct 2004
          : 48
          : 10
          Affiliations
          [1 ] Gilead Sciences, Inc., Foster City, CA 94402, USA. wdelaney@gilead.com
          Article
          48/10/3702
          10.1128/AAC.48.10.3702-3710.2004
          15388423
          9996f8c6-0e41-4514-8bd1-9bb7eac60545
          History

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