Virological characterization of treatment failures and retreatment outcomes in patients infected with "unusual" HCV genotype 1 subtypes.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
13
12
2022
accepted:
26
02
2023
medline:
19
7
2023
pubmed:
1
4
2023
entrez:
31
3
2023
Statut:
ppublish
Résumé
Suboptimal rates of sustained virological response have been reported in patients infected with an "unusual," non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment. Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an "unusual" genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy. Patients infected with "unusual" HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. "Unusual" HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.
Sections du résumé
BACKGROUND AND AIMS
Suboptimal rates of sustained virological response have been reported in patients infected with an "unusual," non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment.
APPROACH AND RESULTS
Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an "unusual" genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy.
CONCLUSIONS
Patients infected with "unusual" HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. "Unusual" HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.
Identifiants
pubmed: 36999537
doi: 10.1097/HEP.0000000000000379
pii: 01515467-202308000-00023
doi:
Substances chimiques
Antiviral Agents
0
Viral Nonstructural Proteins
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-620Investigateurs
Florence Abravanel
(F)
Corinne Amiel
(C)
Laurence Bocket
(L)
Ségolène Brichler
(S)
Étienne Brochot
(É)
Élisabeth André-Garnier
(É)
Catherine Gaudy-Graffin
(C)
Lucile Larrouy
(L)
Anne-Marie Roque-Afonso
(AM)
Caroline Scholtes
(C)
Vincent Thibault
(V)
Ève Todesco
(È)
Pascale Trimoulet
(P)
Édouard Tuaillon
(É)
Aurélie Velay
(A)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 American Association for the Study of Liver Diseases.
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