Objective:To address HBV serum nucleic acid markers for stages without apparent replica- tion.Methods:DNA and RNA sequence segments from the X,C and pre C/C regions produced succes- sively during replication were used as targets for quantitative PCR and RT/PCR.Results:The assays con- firmed the preferential formation of intermediates blocked at early stages.They persisted as the only de- tectable type of serum HBV DNA even after one year of therapy.At reentry into viral replication due to e- mergence of drug resistant mutants,lamivudine resistance produced exclusively incomplete DNA minus strands,whereas the wild type virus immediately synthesized complete DNA minus strands.Conclusion: PCR assays used for monitoring complete suppression of HBV replication must target the X gene region.
