Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.
Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.
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DOI：
10.1056/nejmoa1501315
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发表时间：
2015-08-20
期刊：
影响因子：
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通讯作者：
ION-4 Investigators
中科院分区：
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作者：
Naggie S;Cooper C;Saag M;Workowski K;Ruane P;Towner WJ;Marks K;Luetkemeyer A;Baden RP;Sax PE;Gane E;Santana-Bagur J;Stamm LM;Yang JC;German P;Dvory-Sobol H;Ni L;Pang PS;McHutchison JG;Stedman CA;Morales-Ramirez JO;Bräu N;Jayaweera D;Colson AE;Tebas P;Wong DK;Dieterich D;Sulkowski M;ION-4 Investigators
对合并人类免疫缺陷病毒1型（HIV-1）的丙型肝炎病毒（HCV）患者的有效治疗仍然是一个未满足的医疗需求。我们进行了一项多中心、单组、开放标签的研究，涉及同时感染HIV-1和基因型1或4型HCV的患者，他们接受替诺福韦和恩曲他滨与依非韦伦、利匹韦林或雷替格拉韦的抗逆转录病毒治疗。所有患者均接受NS5A抑制剂ledipasvir和核苷酸聚合酶抑制剂sofosbuvir单次固定剂量联合治疗，疗程12周。主要终点是治疗结束后12周的持续病毒学应答。在入组的335名患者中，34%为黑人，55%曾接受过HCV治疗，20%患有肝硬化。总体而言，322例患者（96%）在治疗结束后12周有持续的病毒学应答（95%可信区间[CI]， 93 - 98），其中HCV基因型1a患者96% (95% CI, 93 - 98)， HCV基因型1b患者96% (95% CI, 89 - 99)， HCV基因型4患者100% （95% CI, 63 - 100）。持续病毒学反应的比率是相似的，无论以前的治疗或肝硬化的存在。在13例没有持续病毒学反应的患者中，10例在治疗结束后复发。没有患者证实HIV-1病毒逻辑反弹。最常见的不良事件是头痛（25%）、疲劳（21%）和腹泻（11%）。没有患者因为不良事件而停止治疗。在同时感染HIV-1和HCV基因型1或4的患者中，使用雷地帕韦和索非布韦治疗12周可提供高的持续病毒学应答率。（由Gilead Sciences资助；ION-4 ClinicalTrials.gov编号：NCT02073656）
Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 viro-logic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.)