NS3 Resistance-Associated Variants

• Published in: PloS one 2016-09, Vol.11 (9), p.e0163197
• Main Authors: Jimenez-Sousa, María Ángeles, Gutiérrez-Rivas, Mónica, Álvaro-Meca, Alejandro, García-Álvarez, Mónica, Harrigan, P. Richard, Fedele, Cesare Giovanni, Briz, Verónica, Vázquez-Morón, Sonia, Resino, Salvador
• Format: Article
• Language: English
• Subjects: Analysis; Antiviral agents; Comorbidity; DNA sequencing; Genetic aspects; Hepatitis C virus; Medical research; Proteases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163197

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. 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/). 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