PMID- 22585719
OWN - NLM
STAT- MEDLINE
DCOM- 20120905
LR  - 20131121
IS  - 1096-9071 (Electronic)
IS  - 0146-6615 (Linking)
VI  - 84
IP  - 7
DP  - 2012 Jul
TI  - Factors influencing inadequate or suboptimal response to adefovir with or without 
      genotypic resistance.
PG  - 1030-6
LID - 10.1002/jmv.23270 [doi]
AB  - The aim of the study was to explore the factors in inadequate-responders to 
      treatment with adefovir (ADV) with or without genotypic resistance. The 
      reverse-transcriptase (RT) gene of hepatitis B virus (HBV) was sequenced in 161 
      patients with inadequate-response to ADV and analyzed for HBV genotypes using a 
      phylogenetic approach. Seventy-six patients (47.2%) were found to carry the 
      rtA181V/T/S or rtN236T residue substitution, and most of them had viral rebound. 
      In the patients with viral rebound and ADV genotypic resistance, 19 (25.7%) 
      showed rtA181V/T/S + rtN236T substitutions. In the other patients, it was found 
      that HBV genotypes and cirrhosis influenced the selection of ADV-resistant 
      positions by univariate analysis and multiple logistic regression analysis. The 
      rtN236T was more frequent in patients with genotype B, and the rtA181V/T/S was 
      more common in patients with genotype C (chi(2)  = 11.543, P = 0.001). Multiple 
      logistic regression analysis showed that the rtN236T and time resistant strains 
      occurred during ADV-treatment were statistically significant for influencing 
      rtA181 variation types (P = 0.007 and P = 0.024, respectively), and the 
      occurrence of rtA181T was found to be significantly earlier than rtA181V. In 
      conclusion, genotypic resistance was not detected in the majority of primary 
      nonresponders to ADV when compared to the patients with viral rebound. The 
      different HBV genotypes influence the selection of ADV-resistant mutation 
      positions. The rtA181T occurs more frequently in patients with the rtN236T and it 
      occurs earlier when compared to the rtA181V. These findings suggest that early 
      judgment of adequate response and making a decision for interference in patients 
      treated with ADV are of importance in clinical practice.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Zhou, Xia
AU  - Zhou X
AD  - Department of Infectious Diseases, Southwest Hospital, Third Military Medical 
      University, Chongqing, China.
FAU - Kuang, XueMei
AU  - Kuang X
FAU - Fan, Ke
AU  - Fan K
FAU - Zhang, ChangJiang
AU  - Zhang C
FAU - Deng, GuoHong
AU  - Deng G
FAU - Wang, HuiFen
AU  - Wang H
FAU - Wang, YuMing
AU  - Wang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Organophosphonates)
RN  - 6GQP90I798 (adefovir)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Adult
MH  - Antiviral Agents/*administration & dosage/pharmacology
MH  - DNA, Viral/genetics
MH  - Drug Resistance, Viral
MH  - Female
MH  - Genotype
MH  - Hepatitis B virus/*genetics/isolation & purification
MH  - Hepatitis B, Chronic/*drug therapy/*virology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Organophosphonates/*administration & dosage/pharmacology
MH  - Phylogeny
MH  - RNA-Directed DNA Polymerase/genetics
MH  - Treatment Failure
EDAT- 2012/05/16 06:00
MHDA- 2012/09/06 06:00
CRDT- 2012/05/16 06:00
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/09/06 06:00 [medline]
AID - 10.1002/jmv.23270 [doi]
PST - ppublish
SO  - J Med Virol. 2012 Jul;84(7):1030-6. doi: 10.1002/jmv.23270.