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Background & Aims   ABT ‐530 is a next‐generation hepatitis C virus ( HCV )  NS 5A inhibitor with potent pangenotypic antiviral activity  in vitro . Paritaprevir is an  NS 3/4A protease inhibitor codosed with ritonavir that displays  in vitro  activity against  HCV  genotypes 1–4 and 6.    Methods  Efficacy, pharmacokinetics and safety of  ABT ‐530 with paritaprevir/ritonavir and ribavirin were evaluated in this phase 2, open‐label, multicentre study in treatment‐naïve non‐cirrhotic patients with genotype 3 infection. Ten patients, all genotype 3a, received 120 mg  ABT ‐530 and 150/100 mg paritaprevir/ritonavir once daily with ribavirin for 12 weeks.    Results  Nine (90%) patients achieved a sustained virological response at post‐treatment weeks 12 and 24. One patient experienced virological failure at treatment week 6. Sequence analyses for  HCV  variants in samples from this patient identified A166S in  NS 3 at baseline and after breakthrough, as well as A30K at baseline and linked S24F+M28K+A30K variants in  NS 5A after breakthrough. Neither genotype 3  NS 3 A166S nor  NS 5A A30K variant confers any resistance to paritaprevir or  ABT ‐530 respectively. However, genotype 3  NS 5A S24F+M28K+A30K‐linked variant confers a >5000‐fold increase in  ABT ‐530  EC  50  relative to that of the wild‐type replicon. This patient's  ABT ‐530 exposure was comparable to the cohort, while paritaprevir and ritonavir exposures were the lowest of all patients. No serious or severe adverse events and adverse events leading to early discontinuation were reported.    Conclusions  Results from this study show that  ABT ‐530 holds promise as part of a direct‐acting antiviral treatment regimen for  HCV  genotype 3 infection.

High antiviral activity of NS 5A inhibitor ABT ‐530 with paritaprevir/ritonavir and ribavirin against hepatitis C virus genotype 3 infection