PMID- 10762559
OWN - NLM
STAT- MEDLINE
DCOM- 20000601
LR  - 20181130
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 181
IP  - 4
DP  - 2000 Apr
TI  - Evolution of hepatitis B virus polymerase gene sequence during famciclovir 
      therapy for chronic hepatitis B.
PG  - 1221-33
AB  - Prolonged administration of nucleoside analogues for chronic hepatitis B may 
      result in the emergence of hepatitis B viral polymerase mutants. To gain insight 
      into the mechanism involved in the virus's resistance to famciclovir, the amino 
      acid sequences of the terminal protein and reverse-transcriptase (RT) domains of 
      the viral polymerase were determined during therapy among 28 patients. The 
      antiviral response was independent of viral genotypes, and nonresponse to 
      famciclovir was associated with a complex variability of the RT domain. No 
      mutation in the YMDD motif was observed, whereas an L528M mutation was clearly 
      selected by famciclovir treatment in 2 patients, as well as 14 novel mutations in 
      7 patients. Clone sequence analysis of the RT domains of patients undergoing 
      retreatment with famciclovir and/or lamivudine showed the selection of a 
      preexisting drug-resistant mutant in one case and indicated that sequential 
      antiviral therapy may allow the rapid selection of resistant strains.
FAU - Seigneres, B
AU  - Seigneres B
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) Unit 271, 
      Lyon, France.
FAU - Pichoud, C
AU  - Pichoud C
FAU - Ahmed, S S
AU  - Ahmed SS
FAU - Hantz, O
AU  - Hantz O
FAU - Trepo, C
AU  - Trepo C
FAU - Zoulim, F
AU  - Zoulim F
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20000413
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antiviral Agents)
RN  - 0 (Gene Products, pol)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (P protein, Hepatitis B virus)
RN  - 452-06-2 (2-Aminopurine)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - QIC03ANI02 (Famciclovir)
SB  - IM
MH  - 2-Aminopurine/*analogs & derivatives/therapeutic use
MH  - Adult
MH  - Amino Acid Sequence
MH  - Antiviral Agents/*therapeutic use
MH  - Cloning, Molecular
MH  - Drug Resistance, Microbial/genetics
MH  - *Evolution, Molecular
MH  - Famciclovir
MH  - Female
MH  - Gene Products, pol/chemistry/*genetics
MH  - Hepatitis B e Antigens/analysis
MH  - Hepatitis B virus/*enzymology
MH  - Hepatitis B, Chronic/drug therapy/*enzymology/genetics
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - RNA-Directed DNA Polymerase/chemistry/*genetics
MH  - Sequence Alignment
EDAT- 2000/04/14 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/04/14 09:00
PHST- 1999/06/19 00:00 [received]
PHST- 1999/12/13 00:00 [revised]
PHST- 2000/04/14 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/04/14 09:00 [entrez]
AID - JID990745 [pii]
AID - 10.1086/315368 [doi]
PST - ppublish
SO  - J Infect Dis. 2000 Apr;181(4):1221-33. doi: 10.1086/315368. Epub 2000 Apr 13.