A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine

J Viral Hepat. 2006 Apr;13(4):278-88. doi: 10.1111/j.1365-2893.2005.00712.x.


Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a 2-year period. We evaluated 283 lamivudine-naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load, at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics*
  • Female
  • France
  • Hepatitis B Antibodies / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Prospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Sequence Analysis, DNA
  • Statistics, Nonparametric


  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B e Antigens
  • Reverse Transcriptase Inhibitors
  • Lamivudine