title: [Dissection of mechanism for the adefovir dipivoxil resistance in chronic hepatitis B patients].
abstract: OBJECTIVE
  To explore the mechanism for adefovir dipivoxil (ADV) resistance occurred in chronic hepatitis B patients of a series of phase III clinical trails.
  
  
  METHODS
  30 resistant HBV strains were selected out from 177 cases of ADV treated chronic hepatitis B patients. HBV polymerase RT region were amplified by nested PCR and analyzed with the standard nucleotide sequence of HBV strains deposited in GeneBank.
  
  
  RESULTS
  21 out of 30 HBV strains were primary resistant strains, among them 5 HBV strains (23.8%, 5/21) had the polymorphism site of rtN118H. While the other 9 HBV strains showed secondary resistance, variations in conservative region C (rtM207V) and other non-conservative regions were found. The classic mutation sites such as rtN236T and rtA181V/T were not found.
  
  
  CONCLUSIONS
  Polymorphism site of rtN118H might be responsible for HBV primary resistance to ADV therapy. rtM207V variation in HBV RT C domain and other variation sites might play a role in HBV secondary resistance to ADV treatment, and natural resistant quasispecies may be the basis for the ADV quick resistance. These conclusions await further confirmation by phenotype test.
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. aizhong9@yahoo.com.cn
authors.forename: Ai-Zhong
authors.initials: AZ
authors.lastname: Zeng
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Cai
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Xin
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Guo
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Li
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Deng
authors.forename: Ai-Long
authors.initials: AL
authors.lastname: Huang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000410:Alanine Transaminase; D012194:RNA-Directed DNA Polymerase; D000225:Adenine; C106812:adefovir dipivoxil