Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
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DOI：
10.1056/nejmoa1208953
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发表时间：
2013-01-03
影响因子：
158.5
通讯作者：
Berrey, M. Michelle
中科院分区：
文献类型：
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作者：
Gane, Edward J.;Stedman, Catherine A.;Berrey, M. Michelle
丙型肝炎病毒（HCV）感染的标准治疗是干扰素，皮下注射，可能有麻烦的副作用。我们评估索非布韦，口服核苷酸抑制剂的HCV聚合酶，在干扰素保留和干扰素免费方案治疗HCV infection. METHODS我们提供了开放标签治疗8组患者。共有40例既往未经治疗的HCV基因型2或3型感染患者被随机分为四组;所有四组均接受索非布韦（剂量为400 mg，每日一次）联合利巴韦林治疗12周。其中三组还接受聚乙二醇干扰素α-2a治疗4周、8周或12周。另外两组既往未经治疗的HCV基因型2或3感染患者接受索非布韦单药治疗12周或索非布韦加聚乙二醇干扰素α-2a和利巴韦林治疗8周。两组HCV基因型1感染患者接受索非布韦和利巴韦林治疗12周：10例患者对既往治疗无应答，25例患者既往未接受治疗。我们报告了治疗后24周的持续病毒学应答率。在40例随机分组的患者中，所有10例（100%）接受索非布韦加利巴韦林不加干扰素治疗的患者和所有30例（100%）接受索非布韦加利巴韦林治疗12周加干扰素治疗4周、8周或12周的患者在24周时都有持续病毒学应答。对于其他HCV基因型2或3型感染的患者，所有10例（100%）接受索非布韦加聚乙二醇干扰素α-2a和利巴韦林治疗8周的患者在24周时有持续的病毒学应答，接受索非布韦单药治疗的10例患者中有6例（60%）也有持续的病毒学应答。在HCV基因型1感染的患者中，25例既往未治疗的患者中有21例（84%）和10例既往治疗无应答的患者中有1例（10%）在24周时有持续的病毒学应答。最常见的不良事件是头痛、疲劳、失眠、恶心、皮疹和贫血。结论索非布韦联合利巴韦林治疗12周可能对既往未经治疗的HCV基因型1、2或3型感染患者有效。（由Pharmasset和吉利德科学公司资助; ClinicalTrials.gov编号，NCT 01260350。）
BACKGROUNDThe standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.METHODSWe provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy.RESULTSOf the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia.CONCLUSIONSSofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number, NCT01260350.)