The absence of early resistance-associated substitutions (RASs) selection and the similar dynamics of hepatitis C virus (HCV) kinetics and quasispecies in sustained virological response (SVR) and non-SVR patients after direct-acting antiviral (DAA) therapy initiation suggest that RASs selection may occur at later stages in the remaining reservoir, according to a recent study. Researchers analyzed the potential emergence of RASs immediately after therapy initiation. Samples from 71 patients treated with different DAAs were collected at baseline, during therapy, or until target not detected. HCV-RNA levels were determined by qPCR, and RASs were detected by deep sequencing. They found:

• 63 (89%) patients achieved a SVR, 7 (10%) relapsed, and 1 (1%) experienced a breakthrough.
• Nearly all non-SVR (88%) demonstrated RASs either at baseline or relapse.
• High-frequency RASs at relapse remained detectable at early time point during therapy and reappeared as most prevalent substitutions at relapse.
• Conversely, emergent RASs at relapse were not observed during the first hours/days, before HCV-RNA became detectable.