Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy

AIDS. 2006 Apr 4;20(6):863-70. doi: 10.1097/01.aids.0000218550.85081.59.


Background: Little is known about the prevalence and pattern of hepatitis B virus (HBV) mutations in HIV/HBV co-infected individuals on long-term lamivudine (3TC) therapy.

Methods: HBV polymerase/envelope/basal core promoter/pre-core sequences from 81 HIV-HBV co-infected persons who received at least 6 months 3TC were compared to HBV reference sequences. Host and viral characteristics associated with HBV mutations were determined.

Results: HBV viraemia was detected in 53 persons (65%) and was associated with lower CD4 cell count nadir and higher HIV RNA at the time of testing but not with 3TC duration. Known 3TC-resistant mutations occurred in 50% and 94% of viremic patients with < 2 years and > 4 years 3TC, respectively. The CD4 cell count at testing was significantly higher in those with 3TC-resistant mutations. The triple polymerase mutant (rtL173V, rtL180M, rtM204V), which behaves as a vaccine escape mutant in vitro, occurred in 17% of viraemic patients. Polymerase mutations that may confer resistance to other anti-HBV agents were also detected.

Conclusions: In HIV-HBV co-infected patients, greater immunocompromise is associated with continued HBV viraemia while on 3TC, and development of 3TC-resistant mutations are inevitable with prolonged 3TC use. These mutant viruses may limit future therapeutic options due to cross-resistance or may produce HBV vaccine escape mutants. Thus, timing and selection of antiretroviral therapy is critical in this population.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral / genetics
  • Genes, pol / genetics
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • Hepatitis B / complications*
  • Hepatitis B / drug therapy
  • Hepatitis B / virology
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification
  • Humans
  • Immune Tolerance
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction / methods
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Viral Envelope Proteins / genetics
  • Viral Load
  • Viremia / virology


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Viral Envelope Proteins
  • Lamivudine