Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study
Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An Open-Label Study
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DOI：
10.1093/cid/cix289
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发表时间：
2017-07-01
影响因子：
11.8
通讯作者：
Swain, Mark G.
中科院分区：
文献类型：
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作者：
Feld, Jordan J.;Ramji, Alnoor;Swain, Mark G.
背景与感染其他基因型的患者相比，基因型3型丙型肝炎病毒（HCV）慢性感染患者的疾病进展更快，对当前直接作用的抗病毒治疗方案的反应更低。我们进行了一项开放标签试验，以评估ledipasvir和sofosbuvir加利巴韦林在基因型3 HCV感染患者中的安全性，耐受性和疗效。我们在加拿大的15个研究中心招募了有或没有代偿性肝硬化的初治患者。所有患者均接受ledipasvir-sofosbuvir（90 mg和400 mg）加基于体重的利巴韦林治疗12周。主要终点是治疗后12周的持续病毒学应答（SVR 12）。次要终点包括基线和治疗后出现的耐药性评估。在111例入组患者中，105例（95%）为3a亚型HCV，39例（35%）为代偿性肝硬化。111例患者中有99例达到了SVR 12（89%; 95%置信区间，82%-94%）。在39例肝硬化患者中，31例（79%）达到了SVR 12，而72例无肝硬化患者中有68例（94%）达到了SVR 12。在治疗失败的患者中未发生治疗后出现的耐药突变。1例患者因肝癌停止治疗，并在治疗停止后22天死亡。最常见的不良反应是疲劳（51%）、头痛（36%）和恶心（23%）。在这项涉及基因型3 HCV的初治患者的多中心试验中，12周的ledipasvir-sofosbuvir在没有肝硬化的患者中提供了高水平的SVR。
Background. Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection.Methods. We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance.Results. Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%).Conclusions. In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis.