Virological patterns of hepatitis C virus patients with failure to the current-generation direct-acting antivirals.
Adult
Aged
Aged, 80 and over
Antiviral Agents
/ therapeutic use
Benzimidazoles
/ therapeutic use
Benzofurans
/ therapeutic use
Carbamates
/ therapeutic use
Drug Combinations
Drug Resistance, Viral
Female
Hepacivirus
/ drug effects
Hepatitis C, Chronic
/ drug therapy
Heterocyclic Compounds, 4 or More Rings
/ therapeutic use
Humans
Imidazoles
/ therapeutic use
Liver Cirrhosis
/ virology
Male
Middle Aged
Pyrrolidines
/ therapeutic use
Quinoxalines
/ therapeutic use
Recurrence
Sofosbuvir
/ therapeutic use
Sulfonamides
/ therapeutic use
Treatment Failure
Elbasvir/grazoprevir
Glecaprevir/pibrentasvir
Sofosbuvir/velpatasvir
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
07
02
2020
revised:
15
06
2020
accepted:
21
06
2020
pubmed:
1
7
2020
medline:
20
5
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
There are few data on the virological characterisation of patients with failure to current-generation direct-acting antivirals (DAAs), namely elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir. This study aimed to characterise virological patterns in patients with failure to current DAA regimens as well as the efficacy of re-treatment. All 61 consecutive hepatitis C virus (HCV) treatment-naïve patients with failure to current DAAs from January 2018 to February 2019 were enrolled. Sanger sequencing of NS3, NS5A and NS5B proteins was performed using homemade protocols. NS5A resistance-associated substitutions (RASs) were more frequent in the 17 patients treated with sofosbuvir/velpatasvir (89.5%) and 33 patients treated with elbasvir/grazoprevir (97%) compared with the 11 patients treated with glecaprevir/pibrentasvir (18.2%) (P = 0.002 and 0.000, respectively). NS3 RASs were more often detected in the 33 patients with failure to elbasvir/grazoprevir (30.3%) than in the 11 patients treated with glecaprevir/pibrentasvir (9.1%). NS3 RASs were also detected in 12% of sofosbuvir/velpatasvir-treated patients. NS5B RASs were infrequently identified. Of the glecaprevir/pibrentasvir-treated patients, 73% did not show RASs in any HCV regions, a prevalence higher than that observed in those treated with elbasvir/grazoprevir (0%; P < 0.05) or sofosbuvir/velpatasvir (12%; P < 0.05). Of the 61 patients, 21 (34.4%) were re-treated with sofosbuvir/velpatasvir and voxilaprevir. All patients achieved sustained virological response at 12 weeks (SVR12). To our knowledge, this is one of the first real-life studies describing patients who failed current-generation DAAs; the prevalence of RASs differed according to the DAA regimen used, and the efficacy of re-treatment was high.
Identifiants
pubmed: 32599227
pii: S0924-8579(20)30237-5
doi: 10.1016/j.ijantimicag.2020.106067
pii:
doi:
Substances chimiques
Antiviral Agents
0
Benzimidazoles
0
Benzofurans
0
Carbamates
0
Drug Combinations
0
Heterocyclic Compounds, 4 or More Rings
0
Imidazoles
0
Pyrrolidines
0
Quinoxalines
0
Sulfonamides
0
elbasvir-grazoprevir drug combination
0
glecaprevir and pibrentasvir
0
sofosbuvir-velpatasvir drug combination
0
Sofosbuvir
WJ6CA3ZU8B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106067Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None declared.