Telaprevir Alone or With Peginterferon and Ribavirin Reduces HCV RNA in Patients With Chronic Genotype 2 but Not Genotype 3 Infections
Telaprevir Alone or With Peginterferon and Ribavirin Reduces HCV RNA in Patients With Chronic Genotype 2 but Not Genotype 3 Infections
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DOI：
10.1053/j.gastro.2011.05.046
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发表时间：
2011-09-01
期刊：
影响因子：
29.4
通讯作者：
Beumont, Maria
中科院分区：
文献类型：
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作者：
Foster, Graham R.;Hezode, Christophe;Beumont, Maria
背景与目的：我们评估了单独使用特拉匹韦、聚乙二醇干扰素α-2a和利巴韦林（PR）或所有3种药物（TPR）治疗2周的慢性丙型肝炎病毒（HCV）基因型2或3型感染初治患者的抗病毒活性。方法：我们进行了一项随机、多中心、部分盲法研究，患者（23例HCV基因型2，26例基因型3）接受特拉匹韦（750 mg，每8小时一次）、安慰剂+PR（聚乙二醇干扰素，180 μ g，每周一次和利巴韦林，400 mg，每日两次）或TPR治疗15天，随后PR治疗22或24周。定量HCV RNA的血浆水平。结果：所有HCV基因2型患者的HCV RNA水平均降低，包括接受特拉匹韦单药治疗的患者。在接受特拉匹韦治疗的患者中，下降速度更快。到第15天，0%（telaprevir）、40%（TPR）和22%（PR）的HCV基因型2型患者的HCV RNA水平检测不到;持续病毒学应答率分别为56%、100%和89%。总体而言，9例仅接受特拉匹韦的HCV基因型2患者中有6例在初始应答后15天内出现病毒突破。HCV RNA水平在接受特拉匹韦的HCV基因型3患者中略有下降，在接受PR或TPR的患者中迅速下降（特拉匹韦与PR无协同作用）。在接受特拉匹韦、TPR或PR治疗的患者中，持续病毒学应答率分别为50%、67%和44%; 7例HCV基因型3的患者在治疗后复发（2例接受特拉匹韦治疗，3例接受TPR治疗，2例接受PR治疗），3例HCV基因型3的患者在特拉匹韦单药治疗期间出现病毒突破。各组不良事件的发生率相似。结论：特拉匹韦单药治疗2周可降低慢性HCV基因型2感染患者的HCV RNA水平，但对HCV基因型3患者的活性有限。
BACKGROUND & AIMS: We evaluated antiviral activity of 2 weeks therapy with telaprevir alone, peginterferon alfa-2a and ribavirin (PR), or all 3 drugs (TPR) in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections. METHODS: We performed a randomized, multicenter, partially blinded study of patients (23 with HCV genotype 2, 26 with genotype 3) who received telaprevir (750 mg every 8 h), placebo plus PR (peginterferon, 180 mu g, once weekly and ribavirin, 400 mg, twice daily), or TPR for 15 days, followed by PR for 22 or 24 weeks. Plasma levels of HCV RNA were quantified. RESULTS: Levels of HCV RNA decreased in all patients with HCV genotype 2, including those who received telaprevir monotherapy. The decrease was more rapid among patients who received telaprevir. By day 15, 0% (telaprevir), 40% (TPR), and 22% (PR) of patients with HCV genotype 2 had undetectable levels of HCV RNA; rates of sustained virologic response were 56%, 100%, and 89%, respectively. Overall, 6 of 9 HCV genotype 2 patients that received only telaprevir had viral breakthrough within 15 days after an initial response. HCV RNA levels decreased slightly among patients with HCV genotype 3 who received telaprevir and decreased rapidly among patients given PR or TPR (telaprevir had no synergistic effects with PR). Sustained virologic response rates were 50%, 67%, and 44% among patients given telaprevir, TPR, or PR respectively; 7 patients with HCV genotype 3 relapsed after therapy (2 given telaprevir, 3 given TPR, and 2 given PR) and 3 patients with HCV genotype 3 had viral breakthrough during telaprevir monotherapy. The incidence of adverse events was similar among groups. CONCLUSIONS: Telaprevir monotherapy for 2 weeks reduces levels of HCV RNA in patients with chronic HCV genotype 2 infections, but has limited activity in patients with HCV genotype 3.