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Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain

2018Journal article Restricted access
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dc.contributor.authorPalladino, Claudia
dc.contributor.authorEsteban-Cartelle, Beatriz
dc.contributor.authorMaté-Cano, Irene
dc.contributor.authorSánchez-Carrillo, Marta
dc.contributor.authorResino, Salvador
dc.contributor.authorBriz, Verónica
dc.date.accessioned2023-08-31T19:47:39Z
dc.date.available2023-08-31T19:47:39Z
dc.date.issued2018
dc.date.updated2023-02-09T14:50:48Z
dc.description.abstractResistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients.pt_PT
dc.description.abstractLas sustituciones asociadas a resistencia (RAS) a elbasvir, el nuevo inhibidor de la NS5A del virus de la hepatitis C (VHC), pueden presentar relevancia al limitar su eficacia y conducir al fracaso virológico en pacientes infectados por VHC genotipo 1a (GT1a) a diferencia de lo observado en GT1b y GT4. No existen datos fuera de ensayos clínicos que evalúen la prevalencia y el impacto de grazoprevir/elbasvir en pacientes infectados con GT1a en España. Se llevó a cabo un estudio transversal multicéntrico en 632 pacientes iniciales, en 13 de los cuales no se consiguió amplificar la muestra o no fue válida para alcanzar una secuencia consenso mediante secuenciación de Sanger. Finalmente, se analizaron 617 individuos infectados con VHC-GT1a atendidos en 84 hospitales distribuidos por las 17 comunidades autónomas más las 2 ciudades autónomas que conforman el territorio español. La población de VHC secuenciada se ha usado para identificar RAS a elbasvir, mientras que el patrón mutacional y la sensibilidad farmacológica se confirmaron mediante geno2pheno[HCV]. Los virus portadores de RAS a elbasvir se observaron en el 6,2% de los pacientes infectados con el VHC-G1a. Las RAS más comunes fueron Y93C/H/N y Q30E/H/R (2,4 y 2,3%, respectivamente). Solo el 3,4% de las RAS a elbasvir identificadas confirieron susceptibilidad reducida al fármaco mediante geno2pheno[HCV] que identificó exclusivamente como principales RAS a elbasvir las posiciones Q30H/R (n = 7) y Y93C/H/N (n = 8) como mutaciones simples y Q30H + Y93H (n = 4) y Q30R + Y93H (n = 2) como mutaciones dobles. En nuestra cohorte española con VHCG1a se observó una menor prevalencia de RAS a elbasvir que la reportada previamente en ensayos clínicos realizados en pacientes norteamericanos. Esta información puede ser esencial para el manejo de los pacientes infectados con G1a y guiar la implementación de grazoprevir/elbasvir en España.pt_PT
dc.description.sponsorshipThis study was funded by the Instituto de Salud Carlos III (Ref. PI14CIII/00011 to SR, MPY 1039/14 and PI15CIII/00031 to VB). CP is supported by the Portuguese Fundação para a Ciência e Tecnologia (grant number SFRH/BPD/77448/2011, part of the EDCTP2 programme funded by the European Union). VB is funded by the Miguel Servet programme directed by the Fondo de Investigación Sanitaria [Health Research Fund] (Instituto de Salud Carlos III) (grant number CP13/00098).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPalladino C, Esteban-Cartelle B, Mate-Cano I, Sánchez-Carrillo M, Resino S, Briz V. Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain. Enfermedades Infecciosas y Microbiología Clínica [Internet]. 1 de maio de 2018;36(5):262–7. Disponível em: https://www.sciencedirect.com/science/article/pii/S0213005X1730126Xpt_PT
dc.identifier.doi10.1016/j.eimc.2017.03.008pt_PT
dc.identifier.eid2-s2.0-85019488063
dc.identifier.slugcv-prod-1185523
dc.identifier.urihttp://hdl.handle.net/10451/59112
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationEPIDEMIOLOGY, PATHOGENESIS AND DETERMINANTS OF HIV-1 TRANSMISSION AND DISEASE PROGRESSION IN THE ANGOLAN PERINATAL HIV COHORT APEHC
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0213005X1730126Xpt_PT
dc.subjectDirect-acting antiviral agentspt_PT
dc.subjectGenotype substitutionpt_PT
dc.subjectHepatitis C virus / human immunodeficiency virus-coinfectionpt_PT
dc.subjectElbasvir implementationpt_PT
dc.subjectPrevalencept_PT
dc.subjectAntivirales de acción directapt_PT
dc.subjectSustitución genotípicapt_PT
dc.subjectCoinfección virus de la hepatitis C / virus de la inmunodeficiencia humanapt_PT
dc.subjectImplementación elbasvirpt_PT
dc.subjectPrevalenciapt_PT
dc.titlePrevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spainpt_PT
dc.title.alternativeFrecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en Españapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleEPIDEMIOLOGY, PATHOGENESIS AND DETERMINANTS OF HIV-1 TRANSMISSION AND DISEASE PROGRESSION IN THE ANGOLAN PERINATAL HIV COHORT APEHC
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F77448%2F2011/PT
oaire.citation.endPage267pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage262pt_PT
oaire.citation.titleEnfermedades Infecciosas y Microbiologia Clinicapt_PT
oaire.citation.volume36pt_PT
oaire.fundingStreamOE
person.familyNamePalladino
person.familyNameMaté
person.familyNameResino
person.familyNameBriz
person.givenNameClaudia
person.givenNameIrene
person.givenNameSalvador
person.givenNameVerónica
person.identifier407901
person.identifier.ciencia-id721D-6851-20D5
person.identifier.orcid0000-0002-8148-0928
person.identifier.orcid0000-0002-9045-9581
person.identifier.orcid0000-0001-8783-0450
person.identifier.orcid0000-0003-2297-5098
person.identifier.ridT-4183-2017
person.identifier.scopus-author-id9332849600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.cv.cienciaid721D-6851-20D5 | Claudia Palladino
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication3145c0e5-1ca2-4bdf-b103-9e79218b07cd
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