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dc.contributor.authorJimenez-Sousa, Maria Angeles 
dc.contributor.authorGutiérrez-Rivas, Mónica 
dc.contributor.authorÁlvaro-Meca, Alejandro
dc.contributor.authorGarcia-Alvarez, Monica 
dc.contributor.authorHarrigan, P Richard
dc.contributor.authorFedele, Giovanni 
dc.contributor.authorBriz, Verónica 
dc.contributor.authorVazquez-Moron, Sonia 
dc.contributor.authorResino, Salvador
dc.identifier.citationPLoS One. 2016 Sep 29;11(9):e0163197es_ES
dc.description.abstractBACKGROUND: 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 ( 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.es_ES
dc.description.sponsorshipThis work was supported by grants from Fondo de Investigación de Sanidad (FIS) [PI14CIII/00011 and MPY 1039/14]. Besides, this work was (partially) funded by the RD12/0017/0024 projects as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). MAJS and MGA are supported by Instituto de Salud Carlos III [grant numbers CD13/00013 and CD12/00442, respectively]. VB is supported by the Fondo de Investigación Sanitaria through the Miguel Servet program [grant number CP13/00098].es_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.titleNS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spaines_ES
dc.rights.licenseAtribución-4.0 Internacional*
dc.contributor.funderFondo de Investigaciones Sanitarias
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderInstituto de Salud Carlos III-ISCIII
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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