Authors: Yongwei Li Mingfen Zhu Yunwei Guo Wei Chen Gang Li
Publish Date: 2009/12/12
Volume: 40, Issue: 2, Pages: 155-162
Abstract
The reasons for adefovir dipivoxil ADV treatment failures appear diverse Few studies have reported fulllength hepatitis B virus HBV genome in patients with ADV treatment failures The patients were from a phase III clinical trial that investigated the antiviral response to ADV in China Seven patients had increase in HBVDNA 1 log10 copies/ml above ontreatment nadir at week 52 The serum HBVDNA levels were above 104copies/ml at week 92 in four of them Sixteen fulllength HBV genomes from the four patients at four time points were sequenced using cloning sequencing method The frequency of substitutions at week 52 was higher than at weeks 2816 wt and 9280 HBVDNA reduction was correlated negatively with the frequency of substitutions at the three time points No published ADVresistant mutations were detected The mutations including substitutions in immunogenic epitopes and conserved sites of the polymerase gene were frequent during ADV treatment Amino acid deletions in X gene and basal core promoter/precore mutations appeared before or during ADV treatment The substitutions in immunogenic epitopes mainly of the surface gene and conserved sites of the polymerase gene other than ADVresistant mutations may have influenced antiviral efficacy in the study More potent antiviral drugs may be important to rescue individual patients and for public health safety It is needed to study how these substitutions influence HBV replication disease progression and antiviral treatment efficacy
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