The Effect Of Lamivudine Resistant Associate Mutations To The Sequential Therapy With Other Nucleoside Analogues (NAs)

This research composed of two parts: I the research of patients with YMDD mutant have poor response to add on ADV therapy; II. The HBV quasispecies of one patient with YMDD mutant evolved during salvage therapy.I .The research of patients with YMDD mutant have poor response to add on ADV therapyObjective To investigate characteristics of lamivudine-associated mutation in chronic hepatitis B patients who were not optimal response to sequential antiviral therapy with adefovir dipivoxil and lamivudine. Methods Sixteen lamivudine-resistance patients who were poor response to sequential therapy with add-on adefovir dipivoxil were enrolled. HBV reverse transcriptase region was analyzed by direct sequencing. Results More than three amino acid substitutions (range: 3-6) were demonstrated in these patients. RtM204V/I substitution was found in all these patients and mutants with rtL180M substitution were demonstrated in most cases (14/16). RtA181T/V and rtN236T substitutions were not found by direct sequencing. Other compensatory substitutions were showed, such as rtL229V/M/F (4/16), rtV173L (4/16), rtV207L/M (3/16), rtP109S (2/16), rtN238H(2/16), rtL80I/V(2/16),etc. Conclusions Lamivudine-resistance with multiple substitutions in HBV polymerase region may decrease the efficacy of sequential antiviral therapy with adefovir dipivoxil and lamivudine, even rt181 and rt236 mutations were not detected.II. The HBV quasispecies of one patient with YMDD mutant evolve when received salvage therapy.Objective To investigate the evolution of HBV quasispecies in patients who received sequential antiviral therapy. Methods Sera from one patient who had been found to have multi-drug resistant HBV mutations to lamivudine ,lamivudine+adefovir, and telbivudine were cloned after nested polymerase chain reaction. Results The patterns of mutation were: L80I+M204I; L80I+L180M+ M204I; L80I+A181T+M204I; L80V+M204I.with the administration of NAs ,the quasispecies of the HBV evolve step by step.Conclusions Lamivudine-resistance with multiple substitutions in HBV polymerase region may affect the efficacy of sequential antiviral therapy.