Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in HCV Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan [PublishAheadOfPrint]

Glecaprevir and pibrentasvir are hepatitis C virus (HCV) pangenotypic inhibitors targeting NS3/4A protease and NS5A, respectively. This once-daily, fixed-dose combination regimen demonstrated high SVR12 rates in CERTAIN-1 and CERTAIN-2 studies in Japanese HCV-infected patients, with a low virologic failure (VF) rate (1.2%). There were no VFs among direct acting antiviral (DAA)-treatment-naive genotype (GT)1a- (n=4), GT1b- (n=128), and GT2- (n=97) infected non-cirrhotic patients treated for 8 weeks, or GT1b- (n=38) or GT2- (n=20) infected patients with compensated cirrhosis treated for 12 weeks. Two of 33 DAA-experienced and 2/12 GT3-infected patients treated for 12 weeks experienced VF. Pooled resistance analysis, grouped by HCV subtype, treatment duration, prior treatment experience, and cirrhosis status was conducted. Among DAA-naïve GT1b-infected patients, the baseline prevalence of NS3-D168E was 1.2%, NS5A-L31M was 3.6%, and NS5A-Y93H was 17.6%. Baseline polymorphisms (BP) in NS3 or NS5A were less prevalent in GT2 with the exception of the common L/M31 polymorphism in NS5A. Among DAA-experienced GT1b-infected patients (30/32 experienced to daclatasvir and asunaprevir), the baseline prevalence of NS3-D168E/T/V was 48.4%, NS5A-L31F/I/M/V was 81.3%, NS5A-P32deletion was 6.3%, and NS5A-Y93H was 59.4%. Common BPs in NS3 and/or NS5A had no impact on treatment outcome in GT1- and GT2-infected patients; the impact in GT3-infected patients could not be assessed due to enrollment of diverse subtypes and limited number of patients. The glecaprevir/pibrentasvir combination regimen allows for a simplified treatment option without the need for HCV subtyping or baseline resistance testing for DAA-naïve GT1 or GT2-infected patients.

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