Detection of drug resistant mutant hepatitis B virus strain and its clinical application.

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Treatment of hepatitis B virus with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. Using a sensitive and specific polymerase chain reaction-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough but not detected in any of pretreatment sera. We also detected the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. Cumulative appearance of YMDD mutants increased by time, but became plateau three years from the beginning of the therapy. The final appearance rate of YMDD mutants was 47.6%. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re administration of lamivudine, possibly combined with other anti viral therapy, might be useful in some patients experiencing hepatitis with lamivudine resistant variants.