title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Monash University, Melbourne, VIC, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Audsley
authors.forename: N
authors.initials: N
authors.lastname: Arrifin
authors.forename: L K W
authors.initials: LK
authors.lastname: Yuen
authors.forename: A
authors.initials: A
authors.lastname: Ayres
authors.forename: S M
authors.initials: SM
authors.lastname: Crowe
authors.forename: A
authors.initials: A
authors.lastname: Bartholomeusz
authors.forename: S A
authors.initials: SA
authors.lastname: Locarnini
authors.forename: A
authors.initials: A
authors.lastname: Mijch
authors.forename: S R
authors.initials: SR
authors.lastname: Lewin
authors.forename: J
authors.initials: J
authors.lastname: Sasadeusz
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015684:Gene Products, pol / Q000187:drug effects / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006509:Hepatitis B / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D000068698:Tenofovir; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
chemical_list: D000998:Antiviral Agents; D015684:Gene Products, pol; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine