Hepatitis C virus early kinetics and resistance-associated substitution dynamics during antiviral therapy with direct-acting antivirals

Journal of Viral Hepatitis
Elena PerpiñánSofía Pérez-Del-Pulgar

Abstract

The emergence of resistance-associated substitutions (RASs) can compromise the high efficacy of direct-acting antivirals (DAAs). Little is known about RASs selection at very early time points during DAA treatment. Therefore, we analyzed the potential emergence of RASs immediately after therapy initiation. Samples of 71 patients treated with different DAAs were collected at baseline, during therapy (hours 4 and 8; days 1-7; weeks 2-4) or until target not detected. HCV-RNA levels were determined by qPCR, and RASs were detected by deep sequencing. Sixty-three (89%) patients achieved a sustained virological response (SVR), 7 (10%) relapsed, and 1 (1%) experienced a breakthrough. Almost all non-SVR (7/8, 88%) showed RASs either at baseline or relapse. High-frequency RASs detected at baseline (Y93H and L159F+C316N) remained detectable at early time points during therapy and reappeared as most prevalent substitutions at relapse. Conversely, emergent RASs at relapse (Q80R, D168E/V, R155K and L31V) were not observed during the first hours-days, before HCV-RNA became undetectable. HCV-RNA decay and genetic evolution of the quasispecies followed a similar pattern during the first hours of therapy in SVR and non-SVR patients. In conclusion...Continue Reading

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Citations

Jul 30, 2020·Viruses·Sylwia OsuchKamila Caraballo Cortés
Oct 2, 2020·Journal of Clinical Microbiology·María Eugenia SoriaCelia Perales
Nov 5, 2019·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Zhenqiu LiuXingdong Chen
Jun 22, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Lone W MadsenAnne Øvrehus

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