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

Yongwei Li1, Mingfen Zhu, Yunwei Guo

  • 1Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Virus Genes
|December 17, 2009
PubMed

Insights

Adefovir dipivoxil (ADV) treatment failures in hepatitis B virus (HBV) patients were linked to frequent viral mutations, not previously identified ADV-resistant ones. These genetic changes may impact treatment effectiveness and disease progression.

Area of Science:

  • Hepatology
  • Virology
  • Genetics

Background:

  • Adefovir dipivoxil (ADV) is used to treat chronic hepatitis B virus (HBV) infection.
  • Treatment failures with ADV can occur, but the underlying viral genetic factors are not fully understood.
  • Previous studies have limited data on full-length HBV genomes from patients experiencing ADV treatment failure.

Purpose of the Study:

  • To investigate the full-length hepatitis B virus (HBV) genome in patients experiencing adefovir dipivoxil (ADV) treatment failure.
  • To identify viral mutations associated with ADV treatment failure.
  • To explore the potential impact of these mutations on antiviral efficacy.

Main Methods:

  • Sequencing of 16 full-length HBV genomes from four patients who experienced treatment failure during a phase III clinical trial.
  • Analysis of viral substitutions at multiple time points (weeks 28, 52, and 92).
  • Correlation analysis between HBV-DNA levels, viral substitution frequency, and treatment outcomes.

Main Results:

  • No known adefovir dipivoxil-resistant mutations were detected in the studied patients.
  • A higher frequency of viral substitutions was observed at week 52, correlating negatively with HBV-DNA reduction.
  • Mutations in immunogenic epitopes and conserved polymerase gene sites, along with deletions in the X gene and basal core promoter/pre-core mutations, were noted during ADV treatment.

Conclusions:

  • Viral genetic changes, including mutations in epitopes and conserved regions, may contribute to adefovir dipivoxil treatment failure, independent of known resistance mutations.
  • Further research is needed to understand how these specific substitutions influence HBV replication, disease progression, and treatment response.
  • The development of more potent antiviral agents may be crucial for managing ADV treatment failures and ensuring public health.

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