Alqahtani S, Ozaras R, Isakov V, Wyles D, Ferenci P, Feld J J, Calinas F, Gschwantler M, Gane E, Crawford D, Jacobson I M, Dumas E O, King M, Sulkowski M
Johns Hopkins University, Baltimore, MD, USA.
Cerrahpasa Medical School, Istanbul, Turkey.
J Viral Hepat. 2017 Apr;24(4):280-286. doi: 10.1111/jvh.12641. Epub 2016 Dec 9.
High rates of sustained virologic response at post-treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co-dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1-infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non-virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT-PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA <LLOQ. The analysis included a total of 2027 patients. Cumulative proportions of subjects with initial HCV RNA suppression <LLOQ at weeks 1, 2, 4 and 6 were 31%, 81%, 99% and 100%, respectively. SVR12 was achieved by 98%, 97%, 98% and 92% of patients with initial suppression at Weeks 1, 2, 4 and 6, respectively (P=.42, trend test). Across six phase 3 trials of 3D ± RBV, most patients achieved viral suppression by week 2. Time to viral suppression was not associated with subsequent achievement of SVR12, suggesting that on-treatment virologic monitoring may not be necessary with this regimen.
在六项3期试验中，对于慢性基因1型丙型肝炎病毒（HCV）感染的成人患者，使用ombitasvir（OBV，一种NS5A抑制剂）、paritaprevir（一种NS3/4A蛋白酶抑制剂）与ritonavir（PTV/r）联合dasabuvir（DSV，一种NS5B RNA聚合酶抑制剂）（即3D方案），无论是否联用利巴韦林（RBV），治疗后第12周均实现了高持续病毒学应答率（SVR12）。我们评估了有或无肝硬化的患者首次出现HCV RNA值低于定量下限的时间是否与SVR12的实现相关。对参加六项3D±RBV 3期研究的基因1型感染患者的数据进行了分析。经历非病毒学失败的患者被排除在分析之外。使用罗氏COBAS TaqMan RT-PCR检测法测定HCV RNA（定量下限，LLOQ =25 IU/mL）。通过首次HCV RNA抑制周数分析SVR12，定义为HCV RNA <LLOQ。分析共纳入2027例患者。在第1、2、4和6周时，初始HCV RNA抑制<LLOQ的受试者累积比例分别为31%、81%、99%和100%。在第1、2、4和6周时初始抑制的患者中，分别有98%、97%、98%和92%实现了SVR12（P = 0.42，趋势检验）。在六项3D±RBV 3期试验中，大多数患者在第2周时实现了病毒抑制。病毒抑制时间与随后SVR12的实现无关，这表明该方案可能无需进行治疗期间的病毒学监测。
