Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues.
Adult
Aged
Aged, 80 and over
Antiviral Agents
/ therapeutic use
Drug Resistance, Multiple, Viral
/ genetics
Female
Genetic Fitness
Hepatitis B virus
/ drug effects
Hepatitis B, Chronic
/ drug therapy
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Nucleosides
/ therapeutic use
Nucleotides
/ therapeutic use
Prospective Studies
RNA-Directed DNA Polymerase
/ genetics
Reverse Transcriptase Inhibitors
/ therapeutic use
antiviral treatment
hepatitis B
next-generation sequencing
primary resistance
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
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.
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
278-286Informations de copyright
© 2018 John Wiley & Sons Ltd.