Ultra-deep sequencing reveals dynamics of drug Resistance-Associated variants in Hepatitis C viruses: Relevance to treatment outcome and resistance screening

Hepatitis C is a global health issue with approximately 3% of the worlds’ population estimated to be infected with the hepatitis C virus (HCV) Inefficiencies in treatment has led to development of direct-acting antivirals (DAAs) that specifically target HCV proteins involved in the virus’s lifecycle1. One of the major concerns arising from the use of the DAAs is the emergence of resistance-associated variants (RAVs) that affect the efficacy of the drugs. RAVs are generally associated with a fitness cost and the use of ultra-deep pyrosequencing technology has shown that in most treatment naive subjects low frequency circulating strains carry RAVs2. The aim of the study was to investigate i) the clinical relevance of low frequency RAVs; ii) the persistence of RAVs and iii) compensatory mutations in a subset of subjects who had failed boceprevir (SCH503034; protease inhibitor).