BACKGROUND & AIMS Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection. METHODS A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated. CONCLUSIONS Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT02371408. LAY SUMMARY This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.

中文翻译：

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拉维达韦加索非布韦在干扰素初治和治疗的慢性丙型肝炎基因型 4 患者中的有效性

背景与目的 虽然丙型肝炎病毒 (HCV) 和 HCV 基因型 4 (GT4) 的治疗已经变得非常有效，但它仍然非常昂贵，并且需要负担得起的选择，尤其是在资源有限的国家。本研究的目的是评估拉维达韦（一种 NS5A 抑制剂）和索非布韦联合治疗慢性 HCV-GT4 感染患者的疗效和安全性。方法 共招募了 300 名 HCV-GT4 感染患者，分为三组：有或无代偿期 Child-A 肝硬化的初治患者（第 1 组）；接受过干扰素治疗但无肝硬化的患者（第 2 组）；和接受过干扰素治疗的肝硬化患者（第 3 组）。第 1 组和第 2 组接受 ravidasvir 200 mg QD 加 sofosbuvir 400 mg QD 治疗 12 周，并按 1:1 随机分配接受或不接受基于体重的利巴韦林治疗。第 3 组患者接受 ravidasvir 加索非布韦加利巴韦林，并以 1:1 的比例随机分配至 12 周或 16 周的治疗持续时间。主要终点是治疗后 12 周的持续病毒学应答 (SVR12)。结果 共有 298 名患者入组：第 1 组 149 人，第 2 组 79 人，第 3 组 70 人。开始研究的所有患者中有 95.3% 达到了 SVR12，其中 98% 的患者没有肝硬化，91% 的患者肝硬化，无论是初治或干扰素经验。利巴韦林摄入量和既往干扰素治疗史不影响 SVR12 率。未观察到病毒学突破，研究治疗耐受性良好。结论 拉维达韦加索非布韦治疗，联合或不联合利巴韦林，无论之前的基于干扰素的治疗如何，对于伴有和不伴有肝硬化的 HCV-GT4 感染患者，耐受性良好并且与高持续病毒学应答率相关。试验注册号 ClinicalTrials.gov 标识符：NCT02371408。LAY Summary 本研究在 298 名感染 4 型丙型肝炎的患者中评估了新型口服丙型肝炎药物 ravidasvir 与批准的口服药物 sofosbuvir 联合用药的疗效和安全性。我们的结果表明，使用 ravidasvir 加索非布韦联合或不联合利巴韦林的治疗效果显着。在肝硬化患者和非肝硬化患者中耐受性良好且反应率高。