Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B

J Med Virol. 2009 Jul;81(7):1151-6. doi: 10.1002/jmv.21505.

Abstract

A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / genetics
  • Drug Resistance, Viral*
  • Female
  • Gene Products, env / genetics
  • Gene Products, pol / genetics
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Retrospective Studies
  • Sequence Analysis, DNA

Substances

  • Antiviral Agents
  • DNA, Viral
  • Gene Products, env
  • Gene Products, pol
  • Lamivudine