Virus Genes

, Volume 40, Issue 2, pp 155–162

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

  • Yongwei Li
  • Mingfen Zhu
  • Yunwei Guo
  • Wei Chen
  • Gang Li
Article

DOI: 10.1007/s11262-009-0429-z

Cite this article as:
Li, Y., Zhu, M., Guo, Y. et al. Virus Genes (2010) 40: 155. doi:10.1007/s11262-009-0429-z
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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 log10 copies/ml above on-treatment nadir) at week 52. The serum HBV-DNA levels were above 104copies/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.

Keywords

Hepatitis B virus Full-length genome Adefovir Drug resistance 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Yongwei Li
    • 1
    • 2
  • Mingfen Zhu
    • 3
  • Yunwei Guo
    • 1
  • Wei Chen
    • 1
  • Gang Li
    • 1
  1. 1.Department of Infectious DiseasesThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Traditional Chinese MedicineThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  3. 3.Department of Infectious DiseasesThe Sixth Hospital of Shanghai Jiao Tong UniversityShanghaiChina

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