title: Clonal analysis of the quasispecies of antiviral-resistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir.
abstract: BACKGROUND
  Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed.
  
  
  METHODS
  A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced.
  
  
  RESULTS
  3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ≥1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log(10) copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment.
  
  
  CONCLUSIONS
  In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of specific HBV mutants during rescue 3TC+ADV.
authors.affiliation: Ankara University, Institute of Hepatology, Ankara, Turkey.
authors.forename: Ersin
authors.initials: E
authors.lastname: Karatayli
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.forename: Senem C
authors.initials: SC
authors.lastname: Karatayli
authors.forename: Emrah
authors.initials: E
authors.lastname: Cevik
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yakut
authors.forename: Gülseren
authors.initials: G
authors.lastname: Seven
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kabaçam
authors.forename: A Mithat
authors.initials: AM
authors.lastname: Bozdayi
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D016679:Genome, Viral / Q000187:drug effects / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine