Evolution of Resistance-Associated Variants of All-Oral Direct-Acting Antiviral Therapy of Hepatitis C in a Clinical Setting

摘要: Because of the high variability Hepatitis C virus (HCV), it might be important to characterize in vivo evolution resistance-associated mutations (RAVs) direct-acting antivirals (DAAs) different genotypes. NS3-, NS5A- and NS5B-HCV substitutions were studied by next generation sequencing (NGS) on 74 HCVinfected patients who started a DAA regimen. RAVs with frequencies 1% 15% analyzed. Globally, 43, 15, 12 4 infected subtype 1a, 1b, genotype 3a, respectively. The majority (64.8%) had cirrhosis, 70.3% HIV-coinfected 14.9% DAA-experienced. Overall baseline prevalence was 74.3%, 52.2%, 45.9% 36.8% any NS3, NS5B NS5A inhibitors available at that time, respectively, dropped 39.2%, 26.1%, 22.8% 16.2%, when only associated ongoing regimen considered. highest proportion detected 1a (81.4%, p=.026), particularly NS3 region (76.9%, p<.001). Among 7 failing patients, 57.1% sequence showing as species. At time viral relapse two accumulated further missing even minority variants Although almost half showed natural baseline, these did not induce resistance DAAs. A limited role NGS low cut-off suggested our study, detection minor species seems predict selection for resistant failure. impact pre-treatment achievement sustained virologic response is limited.