title: HBV carrying drug-resistance mutations in chronically infected treatment-naive patients.
abstract: BACKGROUND
  Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date.
  
  
  METHODS
  HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis.
  
  
  RESULTS
  There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients.
  
  
  CONCLUSIONS
  HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.
authors.affiliation: Laboratory of Gastroenterology and Hepatology, São Paulo Institute of Tropical Medicine and Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil. gomesmic@yahoo.com.br.
authors.forename: Michele S
authors.initials: MS
authors.lastname: Gomes-Gouvêa
authors.forename: Ariana C
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Rosangela
authors.initials: R
authors.lastname: Teixeira
authors.forename: José R
authors.initials: JR
authors.lastname: Andrade
authors.forename: Adalgisa S P
authors.initials: AS
authors.lastname: Ferreira
authors.forename: Lena M F
authors.initials: LM
authors.lastname: Barros
authors.forename: Rosamar E F
authors.initials: RE
authors.lastname: Rezende
authors.forename: Ana C S Santos
authors.initials: AC
authors.lastname: Nastri
authors.forename: Andrea G B
authors.initials: AG
authors.lastname: Leite
authors.forename: Leonora Z
authors.initials: LZ
authors.lastname: Piccoli
authors.forename: Josiane
authors.initials: J
authors.lastname: Galvan
authors.forename: Simone R S S
authors.initials: SR
authors.lastname: Conde
authors.forename: Manoel C P
authors.initials: MC
authors.lastname: Soares
authors.forename: Dimas A
authors.initials: DA
authors.lastname: Kliemann
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Bertolini
authors.forename: Aline S O
authors.initials: AS
authors.lastname: Kunyoshi
authors.forename: André C
authors.initials: AC
authors.lastname: Lyra
authors.forename: Marcio K
authors.initials: MK
authors.lastname: Oikawa
authors.forename: Luciano V
authors.initials: LV
authors.lastname: de Araújo
authors.forename: Flair J
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Maria C J
authors.initials: MC
authors.lastname: Mendes-Corrêa
authors.forename: João R Rebello
authors.initials: JR
authors.lastname: Pinho
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D001938:Brazil; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D024882:Drug Resistance, Viral / Q000235:genetics*; D015684:Gene Products, pol / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D000068698:Tenofovir / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine