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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4 Citations (Scopus)

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 languageEnglish
Article number223
Number of pages14
JournalVIRUSES-BASEL
VolumeVol. 10
Issue numbern.º 5
DOIs
Publication statusPublished - 26 Apr 2018

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Hepacivirus
Genotype
Treatment Failure
RNA
Polymerase Chain Reaction
Mutation
Population
Therapeutics

Keywords

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

Cite this

Ruben, B., Rute, M., Goncalves, M. D. F., Diogo, I., Carvalho, A. P., Cabanas, J., ... Gomes, P. (2018). Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort. VIRUSES-BASEL, Vol. 10(n.º 5), [223]. https://doi.org/10.3390/v10050223
Ruben, Brandão, ; Rute, Marcelino, ; Goncalves, Maria de Fátima ; Diogo, Isabel ; Carvalho, A P ; Cabanas, Joaquim ; Costa, Inês ; Brogueira, Pedro ; Ventura, F ; Miranda , Ana Cláudia ; Mansinho, Kamal ; Gomes, P. / Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort. In: VIRUSES-BASEL. 2018 ; Vol. Vol. 10, No. n.º 5.
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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-BASEL, vol. Vol. 10, no. n.º 5, 223. https://doi.org/10.3390/v10050223

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort. / Ruben, Brandão, ; Rute, Marcelino,; Goncalves, Maria de Fátima; Diogo, Isabel; Carvalho, A P; Cabanas, Joaquim; Costa, Inês; Brogueira, Pedro; Ventura, F; Miranda , Ana Cláudia ; Mansinho, Kamal; Gomes, P.

In: VIRUSES-BASEL, Vol. Vol. 10, No. n.º 5, 223, 26.04.2018.

Research output: Contribution to journalArticle

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).

KW - Direct-acting antivirals

KW - Hepatitis C virus

KW - NS5A

KW - NS5B

KW - Resistance-associated substitutions

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U2 - 10.3390/v10050223

DO - 10.3390/v10050223

M3 - Article

VL - Vol. 10

JO - VIRUSES-BASEL

JF - VIRUSES-BASEL

SN - 1999-4915

IS - n.º 5

M1 - 223

ER -