Use of next-generation sequencing in the CHAT study (acute HCV in HIV): effect of baseline resistance-associated NS3 variants on treatment failure

BackgroundThe epidemic of acute HCV infection among HIV-infected men who have sex with men (MSM) is ongoing. Transmission of drug-resistant variants (DRVs) after HCV treatment failure could pose a major threat to the effectiveness of future therapies. We determined the baseline prevalence of pre-existing DRVs in the HCV NS3 protease gene and their effects on the addition of telaprevir (TVR) to standard pegylated interferon and ribavirin (PEG-IFN/RBV) for acute HCV infection in individuals enrolled in a multicentre randomized controlled trial (2013 and 2014).MethodsThe HCV NS3 viral protease was analyzed using Sanger and next-generation sequencing (NGS) for DRVs at baseline (n = 31), and at viral breakthrough following TVR-based treatment (n = 3) or PEG-IFN/RBV alone (n = 2).ResultsSequence analysis indicated that all individuals were infected with HCV genotype 1a. Complete (100%) concordance was seen between Sanger and NGS for high levels of mutant viral populations. The simeprevir-associated Q80K variant...