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- 저자 : ( Yan Luo3 (검색결과 1 건)
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( Christoph Sarrazin ),( Mark S. Sulkowski ),( Preethi Krishnan ),( Rakesh Tripathi ),( Gretja Schnell ),( Yan Xie ),( Daniel E. Cohen ),( Roger Trinh ),( Lino Rodrigues-jr. ),( Yan Luo3,Nancy S. Shul 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: The 3 direct-acting antiviral (3-DAA) regimen of ombitasvir, ritonavir-boosted paritaprevir and dasabuvir ± RBV is approved in the US and EU for treatment of hepatitis C virus (HCV) genotype (GT) 1 infection. Baseline resistance associated variants (RAVs) in HCV NS3 or NS5A can impact response to other DAA regimens; we assessed the prevalence and impact of RAVs on response to the 3-DAA regimen. Methods: Next-generation sequencing (Illumina MiSeq) assessed baseline samples from treatment-naive (PEARL-IV), -experienced (SAPPHIRE- II), or cirrhotic (TURQUOISE-II) GT1a patients who received 3-DAA + RBV, and treatment-experienced (PEARL-II) or cirrhotic (TURQUOISE-III) GT1b patients who received 3-DAA alone. Thresholds of 1 and 15%, respectively, detected the prevalence and impact of baseline RAVs; impact of RAVs conferring ≥ 5-fold resistance to components of the 3-DAA regimen on response was determined by com- paring SVR rates in patients with or without RAVs. Results: SVR rates were 96% and 100% in patients with GT1a and GT1b, respectively. One or more NS5A RAVs were present in 11% of treatment-experienced or cirrhotic GT1a patients, whereas NS5A RAVs were found in 19% of GT1b patients (15% threshold). Similar SVR rates were seen in GT1a patients with or without NS5A RAVs. All GT1b patients with NS5A RAVs, including at position Y93, achieved SVR. NS3 RAVs were uncommon (≤2%). NS3 RAVs were not seen in any of the 14 virologic failures and an NS5B RAV was seen in 1 virologic failure. The presence of the GT1a NS3 Q80K polymorphism had no impact on SVR. Conclusions: Understanding impact of baseline NS5A RAVs on treatment outcomes is important for relevant HCV therapies. Patients with HCV GT1a-infection treated with the 3-DAA regimen + RBV achieved high SVR rates, regardless of the presence of baseline RAVs. All GT1b patients treated with the 3-DAA regimen alone achieved SVR.
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