High antiviral activity of NS5A inhibitor ABT-530 with paritaprevir/ritonavir and ribavirin against hepatitis C virus genotype 3 infection.

Liver International : Official Journal of the International Association for the Study of the Liver
Fred F PoordadJens Kort

Abstract

ABT-530 is a next-generation hepatitis C virus (HCV) NS5A inhibitor with potent pangenotypic antiviral activity in vitro. Paritaprevir is an NS3/4A protease inhibitor codosed with ritonavir that displays in vitro activity against HCV genotypes 1-4 and 6. 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. 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 NS3 at baseline and after breakthrough, as well as A30K at baseline and linked S24F+M28K+A30K variants in NS5A after breakthrough. Neither genotype 3 NS3 A166S nor NS5A A30K variant confers any resistance to paritaprevir or ABT-530 respectively. However, genotype 3 NS5A S24F+M28K+A30K-linked variant confers a >5000-fold increase in ABT-530 EC50 relative to that of the wild-type replicon. ...Continue Reading

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Citations

Jun 22, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jordan J FeldMichael W Fried
Apr 23, 2019·Journal of Viral Hepatitis·Hadas Dvory-SobolHongmei Mo
Mar 4, 2020·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Nadeem AnwarShimul A Shah

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Methods Mentioned

BETA
Assay
biopsy

Clinical Trials Mentioned

NCT02068222
NCT01458535

Software Mentioned

sas

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