Hepatitis B virus infection: resistance to antiviral agents.

Chronic hepatitis B virus (HBV) infection imposes an enormous public health burden. In patients with chronic hepatitis and high levels of viral replication, inhibitors of the virus polymerase can reduce serum titre and favourably affect the inflammatory process in the liver. Lamivudine, a reverse transcriptase inhibitor, is the first nucleoside analogue to be licensed for treatment of chronic HBV infection. Treatment effects a rapid and profound decrease of serum virus titre, with attendant clinical benefit. Unfortunately drug-resistant species may emerge after 6 months of suppressive therapy. Lamivudine-resistant species have specific amino acid substitutions in the HBV-encoded polymerase. Emergence of these species is frequently associated with loss of clinical benefit. Published data suggest that lamivudine-resistant species exhibit cross-resistance to famciclovir, thereby limiting the potential use of famciclovir with lamivudine as combination therapy. Adefovir is under clinical evaluation for treatment of wild-type and lamivudine-resistant HBV. Preliminary data suggest that adefovir achieves potent inhibition of both species. Studies of drug resistance have followed hot-on-the-heels of the development of potent antiviral therapy for chronic HBV.