Utilization of transgenic mice replicating high levels of hepatitis B virus for antiviral evaluation of lamivudine

A recently developed transgenic mouse strain which expresses high levels of hepatitis B virus (HBV) was studied as a model for evaluation of potential chemotherapeutic agents. Lamivudine ([-]2'-deoxy-3'-thiacytidine), known t o reduce hepatitis B viremia in human patients, and zidovudine (3'-azido-3' -deoxythymidine), previously shown to be ineffective for HBV infections in man, were used in parallel in this transgenic animal model. Orally administ ered lamivudine at dosages of 100, 50, and 25 mg/kg per day given once a da y for 21 days significantly decreased serum and liver HBV DNA titers in a d ose-responsive manner. Zidovudine (similar to 22 mg/kg per day) administere d in the drinking water for 21 days was not effective in reducing these HBV parameters as compared to transgenic placebo-treated controls. The serum H BV DNA titers rebounded to high levels 1 week after cessation of lamivudine treatment. Male and female mice responded in a similar manner to these the rapies. The results using this transgenic mouse model were similar to what would be predicted from treatment of HBV-infected human patients with lamiv udine and zidovudine, and indicate these mice may be useful as a small anim al chemotherapeutic model for study of potential HBV inhibitors. (C) 1999 E lsevier Science B.V. All rights reserved.