Use of whole genome sequencing in the Dutch Acute HCV in HIV study: focus on transmitted antiviral resistance

Objective: Within HIV-positive men having sex with men, the epidemic of hepatitis C virus 9HCV) is ongoing. Transmission of resistant variants of HCV after failure of treatment with directly acting antivirals 9DAA) could be a major threat to the effectivity of therapy. We determined whether HCV-resistant variants to DAAs were prevalent amongst patients with an acute HCV infection diagnosed in 2013 and 2014 in the Netherlands. Methods: Target enrichment for viral nucleic acid separation and deep sequencing were used to recover whole HCV genomes of 50 patients with an acute HCV infection. The genomes were assembled by de novo assembly and analysed for known DAA resistance mutations. Results: In acute HCV infected treatment-naive patients, the relevant resistance-associated substitutions were Q80K 940%) in NS3/4a, M28V 924%) and Q30H combined with Y93H 92%) in NS5A and M414T 92%) or S556G 92%) in NS5b. Patients whose HCV infection failed to respond to boceprevir, peginterferon and ribavirin therapy developed mutations in NS3 at position T54A and R155K. Conclusions: Target enrichment and whole genome sequencing were successfully applied directly on clinical samples from patients with an acute HCV infection. (C) 2016 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.