title: Prevalence and characterization of lamivudine-resistant hepatitis B virus mutations in HIV-HBV co-infected individuals.
abstract: OBJECTIVE
  To determine the prevalence of hepatitis B virus (HBV) genotypic resistance to lamivudine, identify risk factors associated with lamivudine resistance, and characterize the pattern of HBV polymerase mutations in patients co-infected with HIV.
  
  
  METHODS
  Retrospective cross-sectional study.
  
  
  METHODS
  Thirty-three chronic HBV-infected patients were identified from a cohort of 1719 HIV-infected individuals. Patient information was collected from case records, HBV DNA was measured on stored serum by polymerase chain reaction, and positive samples underwent sequencing of HBV polymerase, basal core promoter and precore regions.
  
  
  RESULTS
  Three groups of patients were identified: group 1 were viraemic in the absence of lamivudine-resistance mutations, group 2 were viraemic in association with lamivudine-resistance mutations, and group 3 were not viraemic. Group 2 patients with lamivudine-resistant mutations had significantly higher HBV-DNA viral loads but did not differ in duration of lamivudine therapy, HBV genotype, HIV viral load or CD4 cell count compared with patients with wild-type HBV. Group 2 individuals also demonstrated significantly higher serum alanine aminotransferase (ALT) levels than group 1, who were higher than group 3. Unique mutations were detected in HBV polymerase, including rtV173L plus rtL180M plus rtM204V, which occurred in three patients. This virus has the in-vitro characteristics of a 'vaccine escape' mutant of HBV.
  
  
  CONCLUSIONS
  Genotypic HBV lamivudine resistance was found in 39% of HIV-HBV co-infected individuals treated with lamivudine as part of highly active antiretroviral therapy. These patients exhibited significantly elevated HBV viral loads and serum ALT, and three were infected with a lamivudine-resistant HBV strain that was potentially transmissible to HBV-vaccinated individuals.
authors.affiliation: Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Cooley
authors.forename: Anna
authors.initials: A
authors.lastname: Ayres
authors.forename: Angeline
authors.initials: A
authors.lastname: Bartholomeusz
authors.forename: Sharon
authors.initials: S
authors.lastname: Lewin
authors.forename: Suzanne
authors.initials: S
authors.lastname: Crowe
authors.forename: Anne
authors.initials: A
authors.lastname: Mijch
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.forename: Joseph
authors.initials: J
authors.lastname: Sasadeusz
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006509:Hepatitis B / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012044:Regression Analysis; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors; D018709:Statistics, Nonparametric; D014766:Viremia
chemical_list: D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine