Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia

Dig Liver Dis. 2010 Dec;42(12):902-7. doi: 10.1016/j.dld.2010.04.017. Epub 2010 Jun 19.


Objective: To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV) at the early stages of virological breakthrough (serum HBV-DNA 12-345IU/ml) or when HBV-DNA is undetectable.

Methods: Sixty-four HBV-mono-infected patients were enrolled: 25 had virological breakthrough with serum HBV-DNA ranging from 12 to 345IU/ml during first-line LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM+adefovir dipivoxil (ADV) with undetectable serum HBV-DNA (<12IU/ml).

Results: HBV-reverse transcriptase was successfully sequenced in 22 (88.0%) LAM-treated patients with HBV-DNA between 12 and 345IU/ml, and in 12 (30.8%) patients receiving LAM (±ADV) with HBV-DNA<12IU/ml. Drug-resistance mutations were observed in 17 (77.2%) LAM-treated patients with virological breakthrough: 8 M204V, 7 M204I, 1 M204I/V, and 1 A181T. One or ≥2 compensatory mutations were found in 10 (58.8%) and in 4 (23.5%) patients. Drug-resistance mutations were present also in patients with undetectable serum HBV-DNA: M204I was detected in 2 patients receiving LAM-monotherapy, and V84M in 1 patient receiving LAM+ADV.

Conclusion: Overall findings support the existence of drug-resistance mutations even at very low levels of viral replication. The persistence of low-level HBV replication and consequent drug-resistance emergence should be considered when choosing therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adult
  • Aged
  • Antiviral Agents / pharmacology*
  • DNA, Viral
  • Drug Resistance, Viral / genetics*
  • Female
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / pharmacology*
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / pharmacology
  • Viral Load
  • Viremia


  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Lamivudine
  • Adenine
  • adefovir dipivoxil