Queen Marys University of London, Blizard Institute of Cellular and Molecular Science, London, UK.
Gastroenterology. 2011 Sep;141(3):881-889.e1. doi: 10.1053/j.gastro.2011.05.046. Epub 2011 May 31.
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-naïve patients with chronic hepatitis C virus (HCV) genotype 2 or 3 infections.
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 μg, 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.
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.
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.
我们评估了单用特拉匹韦、聚乙二醇干扰素 alfa-2a 和利巴韦林（PR）或全部 3 种药物（TPR）治疗初治慢性丙型肝炎病毒（HCV）基因型 2 或 3 感染者 2 周的抗病毒活性。
我们进行了一项随机、多中心、部分盲法研究，纳入 23 例 HCV 基因型 2 感染者和 26 例 HCV 基因型 3 感染者，他们分别接受特拉匹韦（每 8 小时 750 mg）、安慰剂+PR（聚乙二醇干扰素，180 μg，每周 1 次；利巴韦林，400 mg，每日 2 次）或 TPR 治疗 15 天，随后接受 PR 治疗 22 或 24 周。定量检测血浆 HCV RNA 水平。
所有 HCV 基因型 2 感染者的 HCV RNA 水平均下降，包括接受单用特拉匹韦治疗的感染者。接受特拉匹韦治疗的感染者下降更快。第 15 天，HCV 基因型 2 感染者中 0%（特拉匹韦）、40%（TPR）和 22%（PR）的 HCV RNA 不可检测；持续病毒学应答率分别为 56%、100%和 89%。总体而言，9 例仅接受特拉匹韦治疗的 HCV 基因型 2 感染者中，有 6 例在初始应答后 15 天内病毒学突破。接受特拉匹韦治疗的 HCV 基因型 3 感染者的 HCV RNA 水平略有下降，而接受 PR 或 TPR 治疗的感染者下降迅速（特拉匹韦与 PR 无协同作用）。接受特拉匹韦、TPR 或 PR 治疗的 HCV 基因型 3 感染者的持续病毒学应答率分别为 50%、67%和 44%；3 例 HCV 基因型 3 感染者在治疗后复发（2 例接受特拉匹韦治疗，3 例接受 TPR 治疗），3 例 HCV 基因型 3 感染者在单用特拉匹韦治疗期间病毒学突破。各组不良反应发生率相似。
特拉匹韦单药治疗 2 周可降低慢性 HCV 基因型 2 感染者的 HCV RNA 水平，但对 HCV 基因型 3 感染者活性有限。
