title: Characteristics of adefovir resistance in patients with or without lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year experience.
abstract: OBJECTIVE
  We investigated the 4-year incidence and predictors of adefovir resistance in chronic hepatitis B patients with or without lamivudine (LAM)-resistance treated with adefovir dipivoxil with or without short-term LAM overlapping.
  
  
  METHODS
  One hundred and two LAM-resistant patients and 79 without LAM resistance (36 naïve and 43 prior LAM exposure) treated with adefovir for >12 months were prospectively examined.
  
  
  RESULTS
  Cumulative incidences of adefovir resistance at month 12, 24, 36 and 48 were 3.9, 21.1, 31.8 and 43% respectively in LAM-resistant patients. Cirrhosis was a significant risk factor for adefovir resistance. A similar rate of adefovir resistance was observed for LAM-resistant patients and those with prior LAM exposure without resistance. Regarding LAM-resistant patients, compared with those having hepatitis B virus (HBV) DNA levels <300 copies/ml, patients having HBV DNA levels >10(4) copies/ml at week 24 of therapy had a hazard ratio (HR) of 9.8 for adefovir resistance development, while those without LAM resistance having the same HBV DNA levels at week 48 had a similar HR (9.5). Multidrug-resistant (LAM+adefovir) variants were detected by direct sequencing in three of 35 LAM-resistant patients treated with a switch to adefovir. Two of them had resistant mutations to both drugs on the same viral genome as determined by molecular cloning and sequencing.
  
  
  CONCLUSIONS
  The incidence of adefovir resistance was high in LAM-resistant patients treated with sequential adefovir. High HBV DNA levels at week 24 and 48 of therapy were the strongest predictors for adefovir resistance development in patients with and without LAM resistance respectively.
authors.affiliation: Department of Internal Medicine, Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Chang
authors.forename: Chi-Sin
authors.initials: CS
authors.lastname: Changchien
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D003001:Cloning, Molecular; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D063065:Organophosphonates / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine