Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations

HIV Med. 2009 Apr;10(4):229-35. doi: 10.1111/j.1468-1293.2008.00675.x. Epub 2009 Jan 28.

Abstract

Objectives: The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV-coinfected individuals receiving tenofovir (TDF).

Methods: This retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on-TDF), and 24 also had samples available prior to treatment (pre-TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (+/-3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR-positive samples was sequenced and compared with reference HBV data.

Results: Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3-23 months). Lamivudine (3TC)-resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.

Conclusions: Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.

Publication types

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

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cross-Sectional Studies
  • Drug Resistance, Viral / genetics*
  • Female
  • Gene Products, pol / drug effects
  • Gene Products, pol / genetics*
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Hepatitis B / drug therapy*
  • Hepatitis B / enzymology
  • Hepatitis B / virology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Humans
  • Lamivudine / pharmacology*
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / pharmacology*
  • Organophosphonates / therapeutic use
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Tenofovir
  • Viral Load
  • Viremia / drug therapy
  • Viremia / virology

Substances

  • Antiviral Agents
  • Gene Products, pol
  • Organophosphonates
  • P protein, Hepatitis B virus
  • Lamivudine
  • Tenofovir
  • Adenine