[Dissection of mechanism for the adefovir dipivoxil resistance in chronic hepatitis B patients].
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.
Zeng
Ai-Zhong
AZ
Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. aizhong9@yahoo.com.cn
Lu
Ping
P
Deng
Hui
H
Cai
Su-Fang
SF
Yang
Chun
C
Xin
Xiao-Juan
XJ
Guo
Jin-Jun
JJ
Li
Qing-Ling
QL
Deng
Xiao-Hui
XH
Huang
Ai-Long
AL
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
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