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Jimenez-Sousa MÁ, Gutiérrez-Rivas M, Álvaro-Meca A, et al. NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain. PLoS One. 2016;11(9):e0163197doi: 10.1371/journal.pone.0163197.
Jimenez-Sousa, M. �. �., Gutiérrez-Rivas, M., Álvaro-Meca, A., García-Álvarez, M., Harrigan, P. R., Fedele, C. G., Briz, V., Vázquez-Morón, S., & Resino, S. (2016). NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain. PloS one, 11(9), e0163197. https://doi.org/10.1371/journal.pone.0163197
Jimenez-Sousa, María Ángeles, et al. "NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain." PloS one vol. 11,9 (2016): e0163197. doi: https://doi.org/10.1371/journal.pone.0163197
Jimenez-Sousa MÁ, Gutiérrez-Rivas M, Álvaro-Meca A, García-Álvarez M, Harrigan PR, Fedele CG, Briz V, Vázquez-Morón S, Resino S. NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain. PLoS One. 2016 Sep 29;11(9):e0163197. doi: 10.1371/journal.pone.0163197. eCollection 2016. PMID: 27685471; PMCID: PMC5042525.
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PLoS One. 2016 Sep 29;11(9):e0163197. doi: 10.1371/journal.pone.0163197. eCollection 2016.

NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain.

PloS one

María Ángeles Jimenez-Sousa, Mónica Gutiérrez-Rivas, Alejandro Álvaro-Meca, Mónica García-Álvarez, P Richard Harrigan, Cesare Giovanni Fedele, Verónica Briz, Sonia Vázquez-Morón, Salvador Resino

Affiliations

  1. Viral Infection and Immunity Unit, National Centre for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
  2. Preventive Medicine and Public Health Unit, Faculty of Health Sciences, Rey Juan Carlos College, Alcorcón, Madrid, Spain.
  3. British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
  4. Diagnostic Approach Area, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

PMID: 27685471 PMCID: PMC5042525 DOI: 10.1371/journal.pone.0163197

Abstract

BACKGROUND: Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain.

METHODS: We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014-2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/).

RESULTS: In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p<0.001], respectively). Both the prevalence of Q80K and GT1a clade I were not uniform throughout the country (p<0.001), which ranged from 7.3%-22.2% and 15.7%-42.5%, respectively. The frequency of the Q80K polymorphism was far higher in patients infected with GT1a clade I than in patients infected with GT1a clade II (41.5% vs. 1.6%; p<0.001).

CONCLUSIONS: The prevalence of most resistance-associated variants in NS3 was low in patients infected with HCV GT1a in Spain, except for Q80K (11.1%), which was also notably higher in HIV/HCV-coinfected patients. The vast majority of Q80K polymorphisms were detected in GT1a clade I.

Conflict of interest statement

Dr. Resino reports a service agreement during the conduct of the study with Janssen-Cilag for Q80K diagnostic in HCV infected patients with genotype 1a in Spain. This does not alter our adherence to P

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