YMDD motif mutants in hepatitis B virus polymerase during lamivudine therapy

摘要

The treating effect of nucleoside analog drug, lamivudine, to patients infected with hepatitis B virus (HBV) is limited by the emergence of drug-resistant viral strains upon prolonged therapy. There have been reported that the majority of lamivudineresistant mutants isolated from the patients have mutations within the YMDD motif of the HBV polymerase gene, as YIDD (M550I) or YVDD (M550V). We analyzed clinical progress and virologic resistance in 15 chronic hepatitis B patients treated continuouslywith lamivudine (3TC) for 12 months. Lamivudine resistance was confirmed by identification of mutations in the YMDD motif of the polymerase gene by using a sensitive and specific PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. At 6 months, the mutants in the YMDD motif were detected from 4 of 15 patients (26.6 percent, three YIDD and one YIDD/YVDD). At 12 months, the mutants were detected from 6 of 15 patients (40.0 percent, three YIDD, two YVDD and one YIDD/YVDD).Therefore we must keep up the study on the clinical implications of YMDD motif mutants during lamivudine therapy.