Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
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DOI：
10.1056/nejmoa1402454
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发表时间：
2014-05-15
影响因子：
158.5
通讯作者：
Marcellin, Patrick
中科院分区：
文献类型：
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作者：
Afdhal, Nezam;Zeuzem, Stefan;Marcellin, Patrick
背景：在2期研究中，核苷酸聚合酶抑制剂sofosbuvir和NS5A抑制剂ledipasvir的全口服联合治疗导致先前未经治疗的1型丙型肝炎病毒（HCV）感染患者的持续病毒学应答率很高。方法：我们进行了一项3期开放标签研究，纳入了先前未经治疗的慢性HCV基因型1感染患者。患者按照1:1:1:1的比例随机分配，接受雷地帕韦和索非布韦的固定剂量联合片剂，每天一次，持续12周，雷地帕韦-索非布韦加利巴韦林12周，雷地帕韦-索非布韦24周，或雷地帕韦-索非布韦加利巴韦林24周。主要终点是治疗结束后12周的持续病毒学应答。结果在接受随机分组和治疗的865例患者中，16%患有肝硬化，12%为黑人，67%为HCV基因型1a感染。在接受12周ledipasvir-sofosbuvir治疗的组中，持续病毒学应答率为99%(95%可信区间[CI]， 96至100)；97% （95% CI, 94 - 99）接受12周ledipasvir-sofosbuvir加利巴韦林治疗组；接受24周ledipasvir-sofosbuvir治疗组98% (95% CI, 95 - 99)；而接受24周ledipasvir-sofosbuvir +利巴韦林治疗的组则为99% （95% CI, 97 - 100）。12周组中没有患者因不良事件而停用ledipasvir-sofosbuvir。最常见的不良反应是疲劳、头痛、失眠和恶心。结论每日1次ledipasvir-sofosbuvir联合或不联合利巴韦林治疗12周或24周对先前未经治疗的HCV基因型感染患者非常有效。
BACKGROUNDIn phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.METHODSWe conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.RESULTSOf the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea.CONCLUSIONSOnce-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection.