From the Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany (S.Z.); Royal Free Hospital and University College London School of Medicine, London (G.M.D.); Tartu University Hospital, Tartu, Estonia (R.S.); Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy (A.M.); Medical University of Bialystok, Bialystok, Poland (R.F.); Gilead Sciences, Foster City, CA (R.H.H., A.I., E.S., D.M.B., W.T.S., G.M.S., J.G.M.); Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm (O.W.); Academic Medical Center, Amsterdam (H.W.R.); Medical University of Vienna, Vienna (P.F.); Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, INSERM Unité 955, Créteil, France (C.H.); and Hospital Universitario Val d'Hebron, Barcelona (R.E.).
N Engl J Med. 2014 May 22;370(21):1993-2001. doi: 10.1056/NEJMoa1316145. Epub 2014 May 4.
In 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.
We 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.
Of 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.
Therapy 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. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).
在临床试验中，核苷酸聚合酶抑制剂索非布韦与抗病毒药物利巴韦林联合治疗丙型肝炎病毒（HCV）基因型 2 感染患者，应答率高，而 HCV 基因型 3 感染患者应答率较低。
我们进行了一项研究，纳入了 HCV 基因型 2 或 3 感染患者，其中一些患者曾接受过基于干扰素的治疗方案。我们将 91 例 HCV 基因型 2 感染患者和 328 例 HCV 基因型 3 感染患者按照 4:1 的比例随机分为接受索非布韦-利巴韦林或安慰剂治疗 12 周。根据 3 期临床试验的新数据，基因型 3 感染患者治疗 16 周比 12 周的应答率更高，因此该研究揭盲，所有基因型 3 感染患者的治疗延长至 24 周，安慰剂组终止，研究目标重新定义为描述性，不包括假设检验。主要终点为治疗结束后 12 周持续病毒学应答。
在纳入并接受治疗的 419 例患者中，21%有肝硬化，58%曾接受过基于干扰素的治疗。接受 12 周治疗的 73 例 HCV 基因型 2 感染患者中，68 例（93%；95%置信区间[CI]，85 至 98）达到持续病毒学应答标准，接受 24 周治疗的 250 例 HCV 基因型 3 感染患者中，213 例（85%；95%CI，80 至 89）达到持续病毒学应答标准。基因型 3 感染患者中，无肝硬化患者和肝硬化患者的应答率分别为 91%和 68%。最常见的不良反应为头痛、疲劳和瘙痒。
索非布韦-利巴韦林治疗 12 周用于 HCV 基因型 2 感染患者，治疗 24 周用于 HCV 基因型 3 感染患者，持续病毒学应答率高。（由吉利德科学公司资助；VALENCE 临床试验.gov 编号，NCT01682720）。
