1. Prevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies
- Author
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Marta Grandal, Álvaro Mena, Manuel Delgado, Berta Pernas, Ana Mariño, Hortensia Álvarez, Nieves Valcarce, Ana B. Pérez, Eva Poveda, Andrés Tabernilla, Ángeles Castro-Iglesias, and Pharmaceutical and Pharmacological Sciences
- Subjects
0301 basic medicine ,Male ,Cirrhosis ,viruses ,Hepacivirus ,Viral Nonstructural Proteins ,medicine.disease_cause ,NS5A ,Gastroenterology ,chemistry.chemical_compound ,Genotype ,Prevalence ,education.field_of_study ,Genotype 1a ,virus diseases ,Middle Aged ,Genotype 3 ,Infectious Diseases ,Cohort ,Hepacivirus/classification ,Adult ,RASs ,medicine.medical_specialty ,Hepatitis C virus ,Ribavirin/pharmacology ,Population ,Mutation, Missense ,Antiviral Agents/pharmacology ,Antiviral Agents ,03 medical and health sciences ,Hepatitis C, Chronic/drug therapy ,Virology ,Internal medicine ,Drug Resistance, Viral ,Ribavirin ,medicine ,Humans ,In patient ,education ,business.industry ,Sequence Analysis, DNA ,Hepatitis C, Chronic ,medicine.disease ,digestive system diseases ,Viral Nonstructural Proteins/genetics ,030104 developmental biology ,chemistry ,Amino Acid Substitution ,Mutant Proteins ,Mutant Proteins/genetics ,business ,HCV-infection ,Follow-Up Studies - Abstract
[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. Instituto de Salud Carlos III; CPII14/00014 Instituto de Salud Carlos III; PI10/02166 Instituto de Salud Carlos III; FI14/00557 Instituto de Salud Carlos III; PI13/02266 Instituto de Salud Carlos III; CM15/00233 Instituto de Salud Carlos III; PI15/00713 Instituto de Salud Carlos III; PI16/02159 Xunta de Galicia; IN606A-2016/023 Comisión Interministerial de Ciencia y Tecnología (España); RD12/0017/006
- Published
- 2018