Weill Cornell Medical College, New York, NY 10021, USA.
N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.
BACKGROUND: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
背景：对于慢性丙型肝炎病毒（HCV）基因型 2 或 3 感染者，若不适合使用聚乙二醇干扰素治疗，或之前干扰素治疗无应答者，目前尚无批准的治疗方法。在 2 期临床试验中，包括口服核苷酸聚合酶抑制剂索非布韦在内的方案在 HCV 基因型 2 或 3 感染者中显示出疗效。
方法：我们进行了两项随机、3 期研究，纳入慢性 HCV 基因型 2 或 3 感染患者。在一项试验中，不适合使用聚乙二醇干扰素治疗的患者接受口服索非布韦和利巴韦林（207 例）或匹配安慰剂（71 例）治疗 12 周。在第二项试验中，未对先前干扰素治疗有反应的患者接受索非布韦和利巴韦林治疗 12 周（103 例）或 16 周（98 例）。主要终点为治疗后 12 周持续病毒学应答。
结果：不适合使用聚乙二醇干扰素治疗的患者中，索非布韦和利巴韦林治疗的持续病毒学应答率为 78%（95%置信区间[CI]，72%至 83%），而安慰剂组为 0%（P<0.001）。在先前接受治疗的患者中，12 周治疗的应答率为 50%，16 周治疗的应答率为 73%（差异-23 个百分点；95%CI，-35 至-11；P<0.001）。在两项研究中，基因型 3 感染患者的应答率均低于基因型 2 感染患者，且基因型 3 感染患者中，肝硬化患者的应答率低于非肝硬化患者。最常见的不良事件是头痛、疲劳、恶心和失眠；索非布韦总体停药率较低（1%至 2%）。
结论：对于不适合使用聚乙二醇干扰素和利巴韦林治疗的 HCV 基因型 2 或 3 感染患者，索非布韦和利巴韦林治疗 12 或 16 周是有效的。在 HCV 基因型 2 感染和无肝硬化患者中，疗效增加。在先前接受基因型 3 感染治疗的患者中，16 周治疗明显优于 12 周治疗。（由吉利德科学公司资助；POSITRON 和 FUSION 临床试验.gov 编号，NCT01542788 和 NCT01604850）。
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