NDLI: Full-length hepatitis B virus sequences from naïve patients with fluctuation of viral load during ADV monotherapy

Content Provider	Springer Nature Link
Author	Li, Yongwei Zhu, Mingfen Guo, Yunwei Chen, Wei Li, Gang
Copyright Year	2009
Abstract	The reasons for adefovir dipivoxil (ADV) treatment failures appear diverse. Few studies have reported full-length 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 HBV-DNA (>1 log$_{10}$ copies/ml above on-treatment nadir) at week 52. The serum HBV-DNA levels were above 10$^{4}$copies/ml at week 92 in four of them. Sixteen full-length 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 28(16 wt) and 92(80). HBV-DNA reduction was correlated negatively with the frequency of substitutions at the three time points. No published ADV-resistant 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/pre-core 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 ADV-resistant 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.
Starting Page	155
Ending Page	162
Page Count	8
File Format	PDF
ISSN	09208569
Journal	Virus Genes
Volume Number	40
Issue Number	2
e-ISSN	1572994X
Language	English
Publisher	Springer US
Publisher Date	2009-12-12
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Hepatitis B virus Full-length genome Adefovir Drug resistance Plant Sciences Virology Medical Microbiology
Content Type	Text
Resource Type	Article
Subject	Virology Genetics Medicine Molecular Biology

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