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

HCV Virology Italian Resistance Network (VIRONET-C)

doi:10.1038/s41598-018-26862-y

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

HCV Virology Italian Resistance Network (VIRONET-C)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	8988
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-26862-y
Publication status	Published - 1 Dec 2018
Externally published	Yes

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10.1038/s41598-018-26862-y

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@article{5175942a9bbd4e618f01ee61ba8fabab,

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

abstract = "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-na{\"i}ve 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.",

author = "{HCV Virology Italian Resistance Network (VIRONET-C)} and Ada Bertoli and Sorbo, {Maria Chiara} and Marianna Aragri and Ilaria Lenci and Elisabetta Teti and Ennio Polilli and {Di Maio}, {Velia Chiara} and Laura Gianserra and Elisa Biliotti and Chiara Masetti and Magni, {Carlo F.} and Sergio Babudieri and Nicolini, {Laura A.} and Martina Milana and Pierluigi Cacciatore and Loredana Sarmati and Adriano Pellicelli and Stefania Paolucci and Antonio Crax{\`i} and Filomena Morisco and Palitti, {Valeria Pace} and Massimo Siciliano and Nicola Coppola and Nerio Iapadre and Massimo Puoti and Giuliano Rizzardini and Gloria Taliani and Caterina Pasquazzi and Massimo Andreoni and Giustino Parruti and Mario Angelico and Perno, {Carlo Federico} and Valeria Cento and Francesca Ceccherini-Silberstein and Pietro Andreone and Fausto Baldanti and Giorgio Barbarini and Vincenzo Boccaccio and Lucio Boglione and Matteo Bolis and Stefano Bonora and Vanni Borghi and Giuseppina Brancaccio and Savino Bruno and Bianca Bruzzone and Vincenza Calvaruso and Nicola Caporaso and Antonio Ciaccio and Alessia Ciancio and Piero Colombatto",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-26862-y",

language = "English",

volume = "8",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

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TY - JOUR

T1 - Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy

AU - HCV Virology Italian Resistance Network (VIRONET-C)

AU - Bertoli, Ada

AU - Sorbo, Maria Chiara

AU - Aragri, Marianna

AU - Lenci, Ilaria

AU - Teti, Elisabetta

AU - Polilli, Ennio

AU - Di Maio, Velia Chiara

AU - Gianserra, Laura

AU - Biliotti, Elisa

AU - Masetti, Chiara

AU - Magni, Carlo F.

AU - Babudieri, Sergio

AU - Nicolini, Laura A.

AU - Milana, Martina

AU - Cacciatore, Pierluigi

AU - Sarmati, Loredana

AU - Pellicelli, Adriano

AU - Paolucci, Stefania

AU - Craxì, Antonio

AU - Morisco, Filomena

AU - Palitti, Valeria Pace

AU - Siciliano, Massimo

AU - Coppola, Nicola

AU - Iapadre, Nerio

AU - Puoti, Massimo

AU - Rizzardini, Giuliano

AU - Taliani, Gloria

AU - Pasquazzi, Caterina

AU - Andreoni, Massimo

AU - Parruti, Giustino

AU - Angelico, Mario

AU - Perno, Carlo Federico

AU - Cento, Valeria

AU - Ceccherini-Silberstein, Francesca

AU - Andreone, Pietro

AU - Baldanti, Fausto

AU - Barbarini, Giorgio

AU - Boccaccio, Vincenzo

AU - Boglione, Lucio

AU - Bolis, Matteo

AU - Bonora, Stefano

AU - Borghi, Vanni

AU - Brancaccio, Giuseppina

AU - Bruno, Savino

AU - Bruzzone, Bianca

AU - Calvaruso, Vincenza

AU - Caporaso, Nicola

AU - Ciaccio, Antonio

AU - Ciancio, Alessia

AU - Colombatto, Piero

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048831915&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-26862-y

DO - 10.1038/s41598-018-26862-y

M3 - Article

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 8988

ER -

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

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