Grandal, MartaPernas, BertaTabernilla, AndresMariño, AnaAlvarez, HortensiaValcarce, NievesMena, AlvaroCastro-Iglesias, AngelesPerez, Ana BDelgado, ManuelPoveda, Eva2023-01-252023-01-252018-02-18Grandal M, Pernas B, Tabernilla A, Mariño A, Álvarez H, Valcarce N, et al . Prevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies. J Med Virol. 2018 Jun;90(6):1094-1098.http://hdl.handle.net/10668/12111The 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.enHCV-infectionNS5ARASsgenotype 1agenotype 3AdultAmino Acid SubstitutionAntiviral AgentsDrug Resistance, ViralFollow-Up StudiesGenotypeHepacivirusHepatitis C, ChronicHumansMaleMiddle AgedMutant ProteinsMutation, MissensePrevalenceRibavirinSequence Analysis, DNAViral Nonstructural Proteinsresearch article29427437Restricted AccessAntiviralesAnálisis de secuencia de ADNGenotipoFarmacorresistencia viralHepacivirusHepatitis C crónicaPrevalenciaMutación missenseProteínas mutantesRibavirinaSustitución de aminoácidos10.1002/jmv.250481096-9071https://ruc.udc.es/dspace/bitstream/2183/20798/2/Grndal_Prvlence.pdf