Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy
Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy
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DOI：
10.1007/s00535-017-1328-z
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发表时间：
2017-10-01
影响因子：
6.3
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Suda, Goki;Ogawa, Koji;Sakamoto, Naoya
无干扰素直接作用抗病毒（DAA）治疗失败的丙型肝炎病毒（HCV）感染患者的最佳再治疗方案尚不确定。在这项研究中，我们旨在评估先前对HCV-NS5A抑制剂daclatasvir （DCV）和HCV-NS3抑制剂asunaprevir （ASV）治疗无效的患者再用ledipasvir （LDV）和sofosbuvir （SOF）加药利巴韦林（RBV）治疗12周的疗效和安全性。方法本研究是一项多中心前瞻性研究，纳入了15例DCV/ASV联合治疗失败的1型HCV感染患者。患者接受sofv、LDV和RBV治疗12周，并在基线、治疗期间和治疗后进行体检和血液检查。在基线和复发时，评估NS3/NS5A和NS5B耐药相关变异（RAVs）。结果15例入组患者中，NS3 D168A/V/T/E、NS5A L31I/M/F/V + Y93H、NS5B S282T的RAVs分别为73.3%（11/15）、86.7%（13/15）和0%（0/15）。总体而言，86.7%（13/15）的患者获得了持续的病毒应答，所有患者都完成了治疗。没有患者发生严重的不良事件。2例对SOF、LDV和RBV联合治疗无效的患者为老年女性，她们具有IL28B非tt基因型和基线时L31I/Y93H或NS5A A92 K的NS5A RAVs。结论sofv、LDV和RBV联合治疗对于DCV和ASV联合治疗失败的基因型1型HCV感染患者有效且耐受性良好。因此，将RBV加入DAA治疗中治疗难治性患者可能会改善治疗结果。
Background The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.Methods This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.Results Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7%(13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.Conclusions This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.