Hepatitis B virus antiviral drug resistance: from the laboratory to the patient.

The development and application of nucleoside (and nucleotide) analogues for the treatment of chronic hepatitis B infection will transform the management of this condition. For instance, treatment with lamivudine effects a dramatic and measurable reduction of serum virus titre. This is associated with biochemical and histological improvements. Unfortunately, for the majority, replication resumes when treatment is withdrawn. Prolonged lamividine treatment may be associated with the emergence of drug-resistant species with specific polymerase mutations. Compared with the observed rate for the development of drug resistance observed during monotherapy of HIV infection, resistance is slow to emerge during treatment of hepatitis B. The rate of emergence might be dependent on the rate of infected hepatocyte turnover, which is extremely variable in chronic HBV infection (and significantly slower than infected lymphocyte turnover during HIV infection). Preliminary data suggest that pretreatment serum virus titre may be an important predictor of the development of drug resistance, an observation consistent with preexistance of the resistant virus in the hepatitis B virus quasispecies. Akin to developments in antiviral treatment of HIV infection, further progress in the treatment of chronic hepatitis B will depend on the development of drugs for use in combination therapy.