Journal Article

Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1–4 in Italy

Angelico, Mario, Parruti, Giustino, Ceccherini-Silberstein, Francesca, Palitti, Valeria Pace, Sarmati, Loredana, Coppola, Nicola, Polilli, Ennio, Masetti, Chiara, Paolucci, Stefania, Andreoni, Massimo, Sorbo, Maria Chiara, Babudieri, Sergio, Milana, Martina, Gianserra, Laura, Perno, Carlo Federico, Cacciatore, Pierluigi, Pasquazzi, Caterina, Rizzardini, Giuliano, Aragri, Marianna, Nicolini, Laura A., Bertoli, Ada, Siciliano, Massimo, Morisco, Filomena, Di Maio, Velia Chiara, Iapadre, Nerio, Puoti, Massimo, Craxì, Antonio, Cento, Valeria, Biliotti, Elisa, Pellicelli, Adriano, Taliani, Gloria, Magni, Carlo F., Lenci, Ilaria, Teti, Elisabetta

2018

Overview

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2–45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4–19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1–4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45 / 45/77 / 45/91 / 631/326/596/1905 / 692/308/174 / Adult / Aged / DEAD-box RNA Helicases / Disease resistance / Drug Resistance, Viral - genetics / Female / Genotype / Genotypes / Hepacivirus - genetics / Hepatitis C / Hepatitis C - drug therapy / Hepatitis C - epidemiology / Hepatitis C - genetics / Humanities and Social Sciences / Humans / Infections / Italy - epidemiology / Liver cancer / Liver transplants / Male / Middle Aged / multidisciplinary / Nucleoside-Triphosphatase / Prevalence / RNA-Dependent RNA Polymerase / Science / Science (multidisciplinary) / Serine Endopeptidases / Viral Nonstructural Proteins - genetics / Viral Proteases / Virology / Viruses