Treatment of chronic woodchuck hepatitis virus infection in the Eastern woodchuck (Marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis B virus infection in humans

The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodc huck (Marmota monax), have been established as a model of hepatitis B virus (HBV)-induced disease, Several published studies have used this experiment al animal model system to demonstrate potential antiviral therapies for chr onic HBV infections. However, there has been little comparative information available on compounds used in clinical anti-HBV studies in WHV-infected w oodchucks, thereby making interpretations of the potential relative effecti veness of new antiviral agents in humans more difficult. In this report, us ing a series of placebo-controlled studies, we compared the relative effect iveness of several nucleoside analogues that have been used in clinical tri als for the treatment of chronic HBV infection against WHV replication in c hronically infected woodchucks, Adenine-5'-arabinoside monophosphate (Ara-A MP [vidarabine]), ribavirin, (-)beta-L-2',3'-dideoxy-3'-thiacytidine (3TC [ lamivudine]), and famciclovir (oral prodrug of penciclovir) induced depress ions in viremia and intrahepatic WHV-DNA replication that were consistent w ith their relative effectiveness in anti-HBV human clinical trials, As obse rved in HBV-infected patients, 3' azido-3'-deoxythymidine (AZT [zidovudine] ) had no effect on WHV replication in these studies. These experimental res ults more firmly establish chronic WHV infection in woodchucks as an accura te and predictive model for antiviral therapies against chronic HBV infecti on in humans and provide a baseline for comparative antiviral effects of ot her experimental antiviral agents in the WHV/woodchuck model system.