Antiviral drug resistance in hepatitis B and C

  Six factors have been directly implicated in the emergence of antiviral drug resistant mutants: the magnitude and rate of virus replication, the viral mutation frequency, the intrinsic mutability of the antiviral target site, the selective pressure exerted by the drug, the overall replication fitness of the mutant and the availability of replication space. Both the hepatitis B virus (HBV) and hepatitis C virus (HCV) have long natural histories of infection over many decades, during which each virus adapts via the processes of natural selection to its infected host. In the context of therapeutic intervention using antiviral drugs, escape mutants are selected from the pre‐existing pool of quasispecies. Particular escape mutants emerge as the dominant virus species, replacing those that have become less fit in the changed environment. In the case of HBV, the emergence of lamivudine‐resistant virus can be associated with worsening liver function and progressive liver disease. In the case of HCV, interferon alpha and ribavirin have complex and indirect actions, making the mechanisms of HCV resistance quite different from those of viral resistance in HBV. Molecular mechanisms of resistance to IFN‐based therapy have indicated that treatment failure appears to be multifactorial, reflecting both host and viral elements. The clinical and public health importance of drug‐resistance for the wider community is clear, and improved treatment strategies are urgently required to prevent their continued selection.