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VITO DI MARCO

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

  • Authors: Di Maio V.C.; Barbaliscia S.; Teti E.; Fiorentino G.; Milana M.; Paolucci S.; Pollicino T.; Morsica G.; Starace M.; Bruzzone B.; Gennari W.; Micheli V.; Yu La Rosa K.; Foroghi L.; Calvaruso V.; Lenci I.; Polilli E.; Babudieri S.; Aghemo A.; Raimondo G.; Sarmati L.; Coppola N.; Pasquazzi C.; Baldanti F.; Parruti G.; Perno C.F.; Angelico M.; Craxi A.; Andreoni M.; Ceccherini-Silberstein F.; Andreone P.; Aragri M.; Bertoli A.; Boeri E.; Brancaccio G.; Brunetto M.; Callegaro A.P.; Cenderello G.; Cento V.; Ciaccio A.; Ciancio A.; Cuomo N.; De Santis A.; Di Biagio A.; Di Marco V.; Di Perri G.; Di Stefano M.A.; Gaeta G.B.; Ghisetti V.; Gulminetti R.; Lampertico P.; Landonio S.; Lichtner M.; Lleo A.; Maida I.; Marenco S.; Masetti C.; Mastroianni C.; Minichini C.; Milano E.; Monno L.; Novati S.; Pace Palitti V.; Paternoster C.; Pellicelli A.; Pieri A.; Puoti M.; Rizzardini G.; Ruggiero T.; Rossetti B.; Sangiovanni V.; Santantonio T.; Taliani G.; Toniutto P.; Vullo V.; Zazzi M.
  • Publication year: 2021
  • Type: Articolo in rivista
  • OA Link: http://hdl.handle.net/10447/519597

Abstract

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: 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. Results: 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). Conclusions: 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.