Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C.

Antiviral Agents / pharmacology Drug Resistance, Viral / genetics Drug Therapy, Combination Female Genotype Hepacivirus / genetics Hepatitis C, Chronic / drug therapy Humans Italy / epidemiology Male Phylogeny Sofosbuvir / therapeutic use Sustained Virologic Response Viral Nonstructural Proteins / genetics

HCV direct-acting antivirals failure genotype 3 resistance

Journal

Liver international : official journal of the International Association for the Study of the Liver

ISSN: 1478-3231

Titre abrégé: Liver Int

Pays: United States

ID NLM: 101160857

Informations de publication

Date de publication:
08 2021

Historique:

revised: 29 12 2020

received: 10 11 2020

accepted: 14 01 2021

pubmed: 27 1 2021

medline: 3 8 2021

entrez: 26 1 2021

Statut: ppublish

Résumé

This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P < .001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P < .001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P = .04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P = .002). In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natural NS5A-RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens.

Identifiants

DOI: 10.1111/liv.14797 PMID: 33497016

pubmed: 33497016

doi: 10.1111/liv.14797

doi:

Substances chimiques

Antiviral Agents 0

Viral Nonstructural Proteins 0

Sofosbuvir WJ6CA3ZU8B

Types de publication

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

Langues

eng

Sous-ensembles de citation

Pagination

1802-1814

Investigateurs

P Andreone (P)

M Aragri (M)

A Bertoli (A)

E Boeri (E)

G Brancaccio (G)

M Brunetto (M)

A P Callegaro (AP)

G Cenderello (G)

V Cento (V)

A Ciaccio (A)

A Ciancio (A)

N Cuomo (N)

A De Santis (A)

A Di Biagio (A)

V Di Marco (V)

G Di Perri (G)

M A Di Stefano (MA)

G B Gaeta (GB)

V Ghisetti (V)

R Gulminetti (R)

P Lampertico (P)

S Landonio (S)

M Lichtner (M)

A Lleo (A)

I Maida (I)

S Marenco (S)

C Masetti (C)

C Mastroianni (C)

C Minichini (C)

E Milano (E)

L Monno (L)

S Novati (S)

V Pace Palitti (V)

C Paternoster (C)

A Pellicelli (A)

A Pieri (A)

M Puoti (M)

G Rizzardini (G)

T Ruggiero (T)

B Rossetti (B)

V Sangiovanni (V)

T Santantonio (T)

G Taliani (G)

P Toniutto (P)

V Vullo (V)

M Zazzi (M)

Informations de copyright

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