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dc.contributor.authorGrandal, Marta
dc.contributor.authorPernas, Berta
dc.contributor.authorTabernilla, Andrés
dc.contributor.authorMariño, Ana
dc.contributor.authorÁlvarez, Hortensia
dc.contributor.authorValcarce, Nieves
dc.contributor.authorMena, Alvaro
dc.contributor.authorCastro-Iglesias, Angeles
dc.contributor.authorPérez, Ana B
dc.contributor.authorDelgado, Manuel
dc.contributor.authorPoveda, Eva
dc.description.abstractThe presence of resistance-associated substitutions (RASs) at NS5A region might compromise the efficacy of Direct Acting Antiviral agents (DAAs). HCV resistance at NS5A region is mainly focused on patients with hepatitis C virus (HCV) genotypes 1a (G1a) and 3 (G3) with other factors of poor treatment response (ie cirrhosis, prior treatment-exposure, or HCV-RNA >800 000 IU/mL). Herein, we evaluated in a cohort of HCV G1a and G3 infected patients the prevalence of RASs at domain I NS5A using population-based sequencing and the impact of RASs on the optimization of current therapeutic strategies. The RASs considered as clinically relevant were: M28A/G/T, Q30D/E/H/G/K/L/R, L31M/V/F, H58D, and Y93C/H/N/S for G1a and Y93H for G3. A total of 232 patients naïve to NS5A inhibitors were included (166 G1a, 66 G3). The overall prevalence of NS5A RASs for G1a and G3 patients was low (5.5%) or null, respectively. A high proportion of patients harbored, at least, one factor of poor response (78.9% for G1a, and 75.8% for G3). Overall, the rates of patients harboring NS5A RASs in combination with any of the other factors were low and the vast majority of patients (G1a> 94% and G3 100%) could be treated with standard treatments of 12 weeks without ribavirin. In conclusion, testing NS5A RASs in specific HCV-infected populations (ie G1a & G3, cirrhosis, prior treatment experienced, HCV-RNA >800 000 IU/mL) might be useful to optimize current NS5A-based therapies avoiding ribavirin-related toxicities, and shortening treatment duration in the majority of patients.
dc.subjectgenotype 1a
dc.subjectgenotype 3
dc.subject.meshAmino Acid Substitution
dc.subject.meshAntiviral Agents
dc.subject.meshDrug Resistance, Viral
dc.subject.meshFollow-Up Studies
dc.subject.meshHepatitis C, Chronic
dc.subject.meshMiddle Aged
dc.subject.meshMutant Proteins
dc.subject.meshMutation, Missense
dc.subject.meshSequence Analysis, DNA
dc.subject.meshViral Nonstructural Proteins
dc.titlePrevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies.
dc.typeresearch article
dc.rights.accessRightsopen access
dc.journal.titleJournal of medical virology
dc.journal.titleabbreviationJ Med Virol
dc.organizationInstituto de Investigación Biosanitaria ibs. GRANADA
dc.pubmedtypeJournal Article
dc.pubmedtypeObservational Study
dc.pubmedtypeResearch Support, Non-U.S. Gov't
Appears in Collections:Producción 2020

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