Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues.


Journal

Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672

Informations de publication

Date de publication:
02 2019
Historique:
received: 31 05 2018
revised: 28 08 2018
accepted: 23 09 2018
pubmed: 20 10 2018
medline: 27 6 2020
entrez: 20 10 2018
Statut: ppublish

Résumé

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.

Identifiants

pubmed: 30339311
doi: 10.1111/jvh.13025
doi:

Substances chimiques

Antiviral Agents 0
Nucleosides 0
Nucleotides 0
Reverse Transcriptase Inhibitors 0
RNA-Directed DNA Polymerase EC 2.7.7.49

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

278-286

Informations de copyright

© 2018 John Wiley & Sons Ltd.

Auteurs

Stéphane Chevaliez (S)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Christophe Rodriguez (C)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Lila Poiteau (L)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Alexandre Soulier (A)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Flora Donati (F)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Mélanie Darty-Mercier (M)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

Corinne Pioche (C)

Santé Publique France, Saint-Maurice, France.

Vincent Leroy (V)

Clinique d'Hépatogastroentérologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
INSERM U823, Grenoble, France.

Véronique Brodard (V)

Laboratoire de Virologie, Hôpital Robert Debré, Reims, France.

Fabien Zoulim (F)

Service d'Hépatogastroentérologie, Hospices Civils de Lyon, Lyon, France.
INSERM U1052, Cancer Research Center of Lyon (CRCL), Lyon, France.

Cécile Brouard (C)

Santé Publique France, Saint-Maurice, France.

Christine Larsen (C)

Santé Publique France, Saint-Maurice, France.

Caroline Semaille (C)

Santé Publique France, Saint-Maurice, France.

Françoise Roudot-Thoraval (F)

Department of Public Health, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.

Jean-Michel Pawlotsky (JM)

Department of Virology, Hôpital Henri Mondor, National Reference Center for Viral Hepatitis B, C and D, Université Paris-Est, Créteil, France.
INSERM U955, Créteil, France.

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Classifications MeSH