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. 2021 Aug;41(8):1802-1814.
doi: 10.1111/liv.14797. Epub 2021 Feb 8.

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

Velia Chiara Di Maio  1 , Silvia Barbaliscia  1 , Elisabetta Teti  2 , Gianluca Fiorentino  3 , Martina Milana  4 , Stefania Paolucci  5 , Teresa Pollicino  6 , Giulia Morsica  7 , Mario Starace  8 , Bianca Bruzzone  9 , William Gennari  10 , Valeria Micheli  11 , Katia Yu La Rosa  1 , Luca Foroghi  2 , Vincenza Calvaruso  12 , Ilaria Lenci  4 , Ennio Polilli  13 , Sergio Babudieri  14 , Alessio Aghemo  15 , Giovanni Raimondo  6 , Loredana Sarmati  2 , Nicola Coppola  8   16 , Caterina Pasquazzi  3 , Fausto Baldanti  5 , Giustino Parruti  13 , Carlo Federico Perno  17 , Mario Angelico  4 , Antonio Craxì  12 , Massimo Andreoni  2 , Francesca Ceccherini-Silberstein  1 ; HCV Virology Italian Resistance Network Group (Vironet C)
Collaborators, Affiliations

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

Velia Chiara Di Maio et al. Liver Int. 2021 Aug.

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.

Keywords: HCV; direct-acting antivirals; failure; genotype 3; resistance.

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References

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