Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
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DOI：
10.1056/nejmoa1512612
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发表时间：
2015-12-31
影响因子：
158.5
通讯作者：
Sulkowski, M.
中科院分区：
文献类型：
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作者：
Foster, G. R.;Afdhal, N.;Sulkowski, M.
背景：在2期试验中，核苷酸聚合酶抑制剂sofosbuvir和NS5A抑制剂velpatasvir联合治疗慢性丙型肝炎病毒（HCV）基因型2或3患者的持续病毒学应答率很高。方法：我们进行了两项随机、3期、开放标签的研究，纳入了既往接受过HCV基因型2或3治疗的患者和未接受过此类治疗的患者，包括代偿性肝硬化患者。在一项试验中，HCV基因型为2的患者按1:1的比例随机分配，接受索非布韦-维帕他韦，每日一次，固定剂量联合片剂（134例），或索非布韦加体重利巴韦林（132例），为期12周。在第二项试验中，HCV基因型为3的患者按1:1的比例随机分配，接受sofosbuvir-velpatasvir治疗12周（277例）或sofosbuvir- ribaavirin治疗24周（275例）。这两项试验的主要终点是治疗结束后12周的持续病毒学应答。结果在2型HCV患者中，索非布韦-维帕他韦组持续病毒学应答率为99%(95%可信区间[CI]， 96 ~ 100)，优于索非布韦-利巴韦林组的94% (95% CI, 88 ~ 97) （P = 0.02）。在基因型为3的HCV患者中，索非布韦-维帕他韦组的持续病毒学应答率为95% (95% CI, 92 ~ 98)，优于索非布韦-利巴韦林组的80% （95% CI, 75 ~ 85）
BACKGROUNDIn phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.METHODSWe conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1: 1 ratio to receive sofosbuvir-velpatasvir,in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1: 1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy.RESULTSAmong patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P = 0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P