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

被引：42

作者：

Bertoli, Ada ^{[1
]}

Sorbo, Maria Chiara ^{[1
]}

Aragri, Marianna ^{[1
]}

Lenci, Ilaria ^{[2
]}

Teti, Elisabetta ^{[3
]}

Polilli, Ennio ^{[4
]}

Di Maio, Velia Chiara ^{[1
]}

Gianserra, Laura ^{[5
]}

Biliotti, Elisa ^{[6
]}

Masetti, Chiara ^{[2
]}

Magni, Carlo F. ^{[7
]}

Babudieri, Sergio ^{[8
]}

Nicolini, Laura A. ^{[9
]}

Milana, Martina ^{[2
]}

Cacciatore, Pierluigi ^{[4
]}

Sarmati, Loredana ^{[3
]}

Pellicelli, Adriano ^{[10
]}

Paolucci, Stefania ^{[11
]}

Craxi, Antonio ^{[12
]}

Morisco, Filomena ^{[13
]}

Palitti, Valeria Pace ^{[14
]}

Siciliano, Massimo ^{[15
]}

Coppola, Nicola ^{[16
]}

Iapadre, Nerio ^{[17
]}

Puoti, Massimo ^{[18
]}

Rizzardini, Giuliano ^{[7
]}

Taliani, Gloria ^{[6
]}

Pasquazzi, Caterina ^{[5
]}

Andreoni, Massimo ^{[3
]}

Parruti, Giustino ^{[4
]}

Angelico, Mario ^{[2
]}

Perno, Carlo Federico ^{[19
]}

Cento, Valeria ^{[1
]}

Ceccherini-Silberstein, Francesca ^{[1
]}

机构：

[1] Univ Roma Tor Vergata, Dept Expt Med & Surg, I-00133 Rome, Italy

[2] Univ Hosp Rome Tor Vergata, Hepatol Unit, I-00133 Rome, Italy

[3] Univ Hosp Rome Tor Vergata, Infect Dis Unit, I-00133 Rome, Italy

[4] Pescara Gen Hosp, Infect Dis Unit, I-65124 Pescara, Italy

[5] Sapienza Univ, St Andrea Hosp, Infect Dis Unit, I-00189 Rome, Italy

[6] Sapienza Univ, Umberto Hosp 1, Trop Dis, I-00161 Rome, Italy

[7] ASST Fatebenefratelli Sacco, Div Infect Dis 1, I-20157 Milan, Italy

[8] Univ Sassari, Clin & Expt Med, I-07100 Sassari, Italy

[9] IRCCS AOU San Martino, IST, Infect Dis Unit, I-16132 Genoa, Italy

[10] San Camillo Forlanini Hosp, Hepatol Unit, I-00151 Rome, Italy

[11] Fdn IRCCS Policlin San Matteo, Mol Virol, I-27100 Pavia, Italy

[12] P Giaccone Univ Hosp, Gastroenterol, I-90127 Palermo, Italy

[13] Univ Naples Federico II, Gastroenterol, I-80131 Naples, Italy

[14] Pescara Gen Hosp, Hepatol Unit, I-65124 Pescara, Italy

[15] Univ Cattolica Sacro Cuore, Gastroenterol, I-00168 Rome, Italy

[16] L Vanvitelli Univ Campania, Infect Dis Unit, I-80138 Naples, Italy

[17] S Salvatore Hosp, Infect Dis Unit, I-67100 Laquila, Italy

[18] Osped Niguarda Ca Granda, Infect Dis Unit, I-20162 Milan, Italy

[19] Univ Milan, Haematol & Oncohematol, I-20122 Milan, Italy

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

SIMEPREVIR PLUS SOFOSBUVIR; DIRECT-ACTING ANTIVIRALS; INFECTION; TREATMENT-NAIVE; RESPONSE RATES; OPEN-LABEL; REAL-LIFE; CIRRHOSIS; PIBRENTASVIR; GLECAPREVIR;

D O I：

10.1038/s41598-018-26862-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-naive 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.

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页数：11

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