Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3
Sofosbuvir and Ribavirin in HCV Genotypes 2 and 3
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DOI：
10.1056/nejmoa1316145
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发表时间：
2014-05-22
影响因子：
158.5
通讯作者：
Esteban, Rafael
中科院分区：
文献类型：
--
作者：
Zeuzem, Stefan;Dusheiko, Geoffrey M.;Esteban, Rafael
背景在临床试验中，核苷酸聚合酶抑制剂索非布韦和抗病毒药物利巴韦林的联合治疗在丙型肝炎病毒（HCV）基因型2感染的患者中与高应答率相关，在HCV基因型3感染的患者中与低应答率相关。其中一些人之前接受过基于干扰素的治疗方案。我们将91例HCV基因型2型感染患者和328例HCV基因型3型感染患者以4：1的比例随机分配，接受索非布韦-利巴韦林或安慰剂治疗12周。基于来自3期试验的新数据表明，与12周相比，HCV基因型3感染的患者在治疗16周时具有更高的应答率，研究揭盲，所有基因型3感染的患者的治疗延长至24周，安慰剂组终止，研究的目标被重新定义为描述性的，不包括假设检验。主要终点是治疗结束后12周的持续病毒学应答。在419名入选并接受治疗的患者中，21%患有肝硬化，58%接受过基于干扰素的治疗。73例HCV基因型2型感染患者中有68例（93%; 95%可信区间[CI]，85 - 98）治疗12周，250例HCV基因型3型感染患者中有213例（85%; 95%CI，80 - 89）治疗24周，达到持续病毒学应答标准。在HCV基因3型感染的患者中，无肝硬化和肝硬化患者的应答率分别为91%和68%。最常见的不良事件是头痛、疲劳和瘙痒。结论对HCV基因型2型感染患者使用索非布韦-利巴韦林治疗12周，对HCV基因型3型感染患者使用索非布韦-利巴韦林治疗24周，可产生高持续病毒学应答率。
BACKGROUNDIn clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection.METHODSWe conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4: 1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.RESULTSOf the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus.CONCLUSIONSTherapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response.