Prevalence of single and multiple natural NS3, NS5A and NS5B resistance-associated substitutions in hepatitis C Virus Genotypes 1-4 in Italy

2018

SCIENTIFIC REPORTS

Prevalence of single and multiple natural NS3, NS5A and NS5B resistance-associated substitutions in hepatitis C Virus Genotypes 1-4 in Italy

01 Pubblicazione su rivista

Bertoli Ada, Sorbo Maria Chiara, Aragri Marianna, Lenci Ilaria, Teti Elisabetta, Polilli Ennio, Di Maio Velia Chiara, Gianserra Laura, Biliotti Elisa, Masetti Chiara, Magni Carlo F., Babudieri Sergio, Nicolini Laura A., Milana Martina, Cacciatore Pierluigi, Sarmati Loredana, Pellicelli Adriano, Paolucci Stefania, Craxì Antonio, Morisco Filomena, Palitti Valeria Pace, Siciliano Massimo, Coppola Nicola, Iapadre Nerio, Puoti Massimo, Rizzardini Giuliano, Taliani Gloria, Pasquazzi Caterina, Andreoni Massimo, Parruti Giustino, Angelico Mario, Perno Carlo Federico, Cento Valeria, Ceccherini-Silberstein Francesca, Andreone Pietro, Baldanti Fausto, Barbarini Giorgio, Boccaccio Vincenzo, Boglione Lucio, Bolis Matteo, Bonora Stefano, Borghi Vanni, Brancaccio Giuseppina, Bruno Savino, Bruzzone Bianca, Calvaruso Vincenza, Caporaso Nicola, Ciaccio Antonio, Ciancio Alessia, Colombatto Piero, Cozzolongo Raffaele, D'Ambrosio Cecilia, D'Ettorre Gabriella, De Leonardis Francesco, De Luca Andrea, Di Biagio Antonio, Di Perri Giovanni, Francioso Simona, Gaeta Giovanni Battista, Gasbarrini Antonio, Ghisetti Valeria, Giorgini Alessia, Grieco Antonio, Gubertini Guido, Gulminetti Roberto, Lambiase Lara, Landonio Simona, Lichtner Miriam, Maida Ivana, Marenco Simona, Marinaro Letizia, Maserati Renato, Melis Michela, Menzaghi Barbara, Meregalli Elisa, Micheli Valeria, Niero Fosca, Paoloni Maurizio, Pieri Alessandro, Rendina Maria, Romagnoli Dante, Rossetti Barbara, Ruggiero Tina, Sangiovanni Vincenzo, Starace Mario, Sticchi Laura, Tarquini Pierluigi, Toniutto Pierluigi, Vullo Vincenzo, Zazzi Maurizio

DOI: 10.1038/s41598-018-26862-y

ISSN: 2045-2322

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.