| Evolution of hepatitis B virus polymerase gene sequence during famciclovir therapy for chronic hepatitis B. | |
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MedLine Citation:
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PMID: 10762559 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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B Seignères; C Pichoud; S S Ahmed; O Hantz; C Trépo; F Zoulim |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2000-04-13 |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 181 ISSN: 0022-1899 ISO Abbreviation: J. Infect. Dis. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-06-01 Completed Date: 2000-06-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1221-33 Citation Subset: AIM; IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 271, Lyon, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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2-Aminopurine
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analogs & derivatives*,
therapeutic use Adult Amino Acid Sequence Antiviral Agents / therapeutic use* Cloning, Molecular Drug Resistance, Microbial / genetics Evolution, Molecular* Female Gene Products, pol / chemistry, genetics* Hepatitis B e Antigens / analysis Hepatitis B virus / enzymology* Hepatitis B, Chronic / drug therapy, enzymology*, genetics Humans Longitudinal Studies Male Middle Aged Molecular Sequence Data RNA-Directed DNA Polymerase / chemistry, genetics* Sequence Alignment |
| Chemical | |
Reg. No./Substance:
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0/Antiviral Agents; 0/Gene Products, pol; 0/Hepatitis B e Antigens; 0/P protein, Hepatitis B virus; 104227-87-4/famciclovir; 452-06-2/2-Aminopurine; EC 2.7.7.49/RNA-Directed DNA Polymerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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