Shiffman Mitchell L, Rustgi Vinod, Bennett Michael, Forns Xavier, Asselah Tarik, Planas Vila Ramon, Liu Li, Pedrosa Marcos, Moller Jonathan, Reau Nancy
Liver Institute of Virginia, Bon Secours Health System, Newport News and Richmond, Virginia, USA.
Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA.
Am J Gastroenterol. 2016 Jun;111(6):845-51. doi: 10.1038/ajg.2016.108. Epub 2016 Apr 5.
Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs.
Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs.
Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%) and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role.
In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.
可提高胃内pH值的抑酸剂（ARAs）和质子泵抑制剂（PPIs）会改变抗病毒药物的生物利用度，这对于寻求治疗的慢性丙型肝炎病毒（HCV）感染所致晚期肝病患者尤为重要。利用六项3期研究的综合数据，我们报告了含ombitasvir（OBV，一种NS5A抑制剂）、利托那韦增强的paritaprevir（PTV/r，一种NS3/4A蛋白酶抑制剂）和dasabuvir（DSV，一种NS5B聚合酶抑制剂）的三联直接抗病毒（DAA）方案联合或不联合利巴韦林（RBV）用于接受ARAs和PPIs的HCV 1型患者的安全性和疗效。
既往未接受过治疗或接受过聚乙二醇干扰素/RBV治疗的患者，无论有无代偿性肝硬化，均接受OBV/PTV/r和DSV联合或不联合基于体重的RBV治疗。在接受ARAs的患者中评估持续病毒学应答（SVR）率，定义为治疗后12周时HCV RNA低于定量下限（SVR12）以及安全性。
在2053例入组并接受研究药物治疗的患者中，410例（20%）接受了ARAs；其中，308例（15%）同时服用PPIs。接受ARAs的患者中SVR12率为95.9%（95%置信区间（CI）93.5 - 97.4%），未接受ARAs的患者中为96.3%（95% CI 95.3 - 97.2%）。同样，在接受或未接受PPI的患者中，SVR12分别为95.1%（95% CI 92.1 - 97.0%）和96.4%（95% CI 95.5 - 97.2%）。无论治疗方案（联合或不联合RBV）以及接受标准剂量或高剂量PPI的患者，应答率均较高。关于安全性，接受ARAs的患者更频繁报告不良事件和严重不良事件，尽管基线人群差异可能也起到了一定作用。
在HCV 1型感染患者中进行的OBV/PTV/r加DSV和RBV的3期试验中，无论是否使用ARAs/PPI或PPI剂量如何，SVR12率均较高。这些数据支持该方案与包括PPIs在内的ARAs联合使用。
