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发表于 2004-4-30 07:54
No Evidence of Resistance to Entecavir in Patients Treated for One Year Despite the Presence of Lamivudine Mutations at Study Entry
Currently in Phase III development, entecavir (ETV) is a highly potent and selective inhibitor of hepatitis B virus (HBV).?All three doses of ETV (1.0, 0.5 and 0.1 mg) showed superiority to continued LVD in reducing HBV DNA over 48 wk in Phase II Study AI463-014.?
Patients isolates were monitored for ETV resistance by genotypic analysis of RT sequences amplified from serum HBV samples.?
Results
At study entry, 132 (87%) of 181 patients treated had isolates that harbored LVDR substitutions L180M and M204V/I. Subsequent genotypic analysis of patient HBV isolates showed no apparent correlation between virologic response on ETV and either LVD-resistant or novel HBV RT substitutions.
Analysis of HBV isolates with paired baseline and on treatment samples showed that most patients with LVDR HBV at study entry retained their LVDR genotypes over 48 wk, regardless of the treatment arm, with a small proportion of isolates showing shifts among their LVDR substitutions.
There was no apparent correlation between these observed changes and ETV dose level. Comparison of 132 paired isolates (108 ETV and 24 LVD) showed no significant difference in the number of other RT substitutions, either in naturally polymorphic positions or in highly conserved residues.
A small number of substitutions at conserved residues did emerge on ETV therapy, but none were correlated with virologic rebounds or reduced susceptibility to ETV.?
THe authors conclude, 揟here was no evidence of resistance emergence in patients treated with ETV for 48 wk despite the presence of LVDR mutations at study entry.?/span>
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford CT, USA.
04/28/04
Reference
R Colonno and others. ABSENCE OF ENTECAVIR RESISTANCE EMERGENCE IN LAMIVUDINE-REFRACTORY PATIENTS TREATED FOR AT LEAST ONE YEAR WITH ENTECAVIR IN STUDY AI463-014. Abstract 43. 39th EASL. April 14-18, 2004. Berlin, Germany.
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