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Title: Prevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies.
Authors: Grandal, Marta
Pernas, Berta
Tabernilla, Andrés
Mariño, Ana
Álvarez, Hortensia
Valcarce, Nieves
Mena, Alvaro
Castro-Iglesias, Angeles
Pérez, Ana B
Delgado, Manuel
Poveda, Eva
Keywords: HCV-infection;NS5A;RASs;genotype 1a;genotype 3
metadata.dc.subject.mesh: Adult
Amino Acid Substitution
Antiviral Agents
Drug Resistance, Viral
Follow-Up Studies
Hepatitis C, Chronic
Middle Aged
Mutant Proteins
Mutation, Missense
Sequence Analysis, DNA
Viral Nonstructural Proteins
Issue Date: 12-Mar-2018
Abstract: The 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.
metadata.dc.identifier.doi: 10.1002/jmv.25048
Appears in Collections:Producción 2020

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