Antiviral resistance in hepatitis B

= Abstract = A high rate of viral turnover, combined with an error‐prone polymerase, results in an increased frequency of mutational events during hepatitis B virus (HBV) replication, resulting in a diverse population of progeny virus (quasispecies). Not suprising then, particular selection pressures, both from within (host immune clearance) or from outside (vaccines and antivirals) the host, readily select out new “escape” mutants resulting in treatment failure. The introduction of nucleos(t)ide analogue (NA) therapy for chronic hepatitis B has resulted in the emergence of antiviral drug resistance which has itself become the major factor limiting treatment effectiveness. Furthermore, due to the overlap of the viral polymerase and envelop reading frames in the circular HBV DNA genome, NA‐resistance associated mutations selected within the catalytic domains of the polymerase usually result in significant changes to the neutralising antibody binding domains of the hepatitis B surface antigen, including the emergence of antiviral drug associated potential vaccine escape mutants (ADAPVEM’s). The main reason for this is that the neutralisation domain, the “a” determinant, is a conformational epitope. The public health significance of APADVEM’s may then be very considerable in terms of the global program for control of hepatitis B via universal infant immunisation. Thus, prevention of resistance requires the adoption of strategies that not only effectively control active HBV replication but also prevent the emergence of APADVEMs.