Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Brandão,  Ruben; Marcelino, Rute; Maria de Fátima Goncalves; Isabel Diogo; A P Carvalho; Joaquim Cabanas; Inês Costa; Pedro Brogueira; F Ventura; Ana Cláudia  Miranda; Kamal Mansinho; P Gomes

doi:10.3390/v10050223

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Brandão, Ruben, Marcelino, Rute, Maria de Fátima Goncalves, Isabel Diogo, A P Carvalho, Joaquim Cabanas, Inês Costa, Pedro Brogueira, F Ventura, Ana Cláudia Miranda , Kamal Mansinho, P Gomes

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Abstract

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).

Original language	English
Article number	223
Number of pages	14
Journal	Viruses
Volume	Vol. 10
Issue number	n.º 5
DOIs	https://doi.org/10.3390/v10050223
Publication status	Published - 26 Apr 2018

Keywords

Direct-acting antivirals
Hepatitis C virus
NS5A
NS5B
Resistance-associated substitutions

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/v10050223Licence: CC BY

Characterization of NS5A and NS5BFinal published version, 1.39 MBLicence: CC BY

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Ruben, B., Rute, M., Goncalves, M. D. F., Diogo, I., Carvalho, A. P., Cabanas, J., Costa, I., Brogueira, P., Ventura, F., Miranda , A. C., Mansinho, K., & Gomes, P. (2018). Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort. Viruses, Vol. 10(n.º 5), Article 223. https://doi.org/10.3390/v10050223

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title = "Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort",

abstract = "This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).",

keywords = "Direct-acting antivirals, Hepatitis C virus, NS5A, NS5B, Resistance-associated substitutions",

author = "Brand{\~a}o, Ruben and Marcelino, Rute and Goncalves, {Maria de F{\'a}tima} and Isabel Diogo and Carvalho, {A P} and Joaquim Cabanas and In{\^e}s Costa and Pedro Brogueira and F Ventura and Miranda, {Ana Cl{\'a}udia} and Kamal Mansinho and P Gomes",

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Ruben, B, Rute, M, Goncalves, MDF, Diogo, I, Carvalho, AP, Cabanas, J, Costa, I, Brogueira, P, Ventura, F, Miranda , AC, Mansinho, K & Gomes, P 2018, 'Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort', Viruses, vol. Vol. 10, no. n.º 5, 223. https://doi.org/10.3390/v10050223

TY - JOUR

T1 - Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

AU - Ruben, Brandão,

AU - Rute, Marcelino,

AU - Goncalves, Maria de Fátima

AU - Diogo, Isabel

AU - Carvalho, A P

AU - Cabanas, Joaquim

AU - Costa, Inês

AU - Brogueira, Pedro

AU - Ventura, F

AU - Miranda , Ana Cláudia

AU - Mansinho, Kamal

AU - Gomes, P

PY - 2018/4/26

Y1 - 2018/4/26

N2 - This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).

AB - This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).

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KW - NS5A

KW - NS5B

KW - Resistance-associated substitutions

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ER -

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Abstract

Keywords

UN SDGs

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