6 周 Ledipasvir-索磷布韦治疗 HIV 合并感染的急性丙型肝炎病毒基因型 1 或 4 感染：一项开放标签、单臂试验。
Ledipasvir-sofosbuvir for 6 weeks to treat acute hepatitis C virus genotype 1 or 4 infection in patients with HIV coinfection: an open-label, single-arm trial.
机构信息
University Hospital, Bonn, Germany.
Royal Free Hospital, London, UK.
出版信息
Lancet Gastroenterol Hepatol. 2017 May;2(5):347-353. doi: 10.1016/S2468-1253(17)30003-1. Epub 2017 Mar 1.
BACKGROUND
The latest European Association for the Study of the Liver (EASL) guidelines now recommend that patients with acute hepatitis C virus (HCV) infection should be treated with a combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, particularly in HIV-coinfected individuals, remains unknown. We assessed the efficacy and safety of 6 weeks of ledipasvir-sofosbuvir for acute genotype 1 or 4 HCV in HIV-1-coinfected patients.
METHODS
This open-label, single-arm trial, done in Germany and the UK, included patients with acute HCV genotype 1 or 4 and HIV-1. At screening, patients were either receiving HIV antiretrovirals and had HIV RNA less than 200 copies per mL, or not receiving antiretrovirals and had a CD4 T-cell count of greater than 500 cells per μL. All patients received ledipasvir-sofosbuvir once daily for 6 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT02457611.
FINDINGS
Between June 11, 2015, and Jan 8, 2016, we enrolled and treated 26 patients. All (100%) were men, 24 (92%) were white, and 25 (96%) were receiving antiretroviral treatment. 19 (73%) had genotype 1a and seven (27%) had genotype 4 HCV. Overall, 20 (77%; 95% CI 56-91) of 26 patients achieved SVR12: 15 (79%) of 19 with genotype 1a, and five (71%) of seven with genotype 4. Of six patients not achieving SVR12, three relapsed, two achieved sustained virological response 4 weeks after the end of treatment but were lost to follow-up, and one was reinfected. The most common adverse events were fatigue (seven participants [27%]), nasopharyngitis (seven [27%]), and headache (six [23%]). No patient discontinued or interrupted therapy due to adverse events. No HIV rebound occurred during the study.
INTERPRETATION
The rate of cure with a fixed-dose combination of ledipasvir-sofosbuvir for patients with acute genotype 1 or 4 HCV infection and HIV-1 coinfection is similar to historic rates with interferon-based treatment, but with shorter treatment duration and more favourable safety outcomes.
FUNDING
Gilead Sciences.
背景
最新的欧洲肝脏研究协会 (EASL) 指南建议急性丙型肝炎病毒 (HCV) 感染患者应采用索磷布韦和 NS5A 抑制剂联合治疗 8 周。然而，无干扰素方案的理想治疗持续时间，特别是在 HIV 合并感染患者中，仍不清楚。我们评估了 6 周 ledipasvir-sovaldi 在 HIV-1 合并感染的急性基因型 1 或 4 HCV 患者中的疗效和安全性。
方法
这是一项在德国和英国进行的开放性、单臂试验，纳入了急性 HCV 基因型 1 或 4 和 HIV-1 合并感染的患者。在筛查时，患者要么正在接受 HIV 抗逆转录病毒治疗，且 HIV RNA 小于 200 拷贝/ml，要么未接受抗逆转录病毒治疗，且 CD4 细胞计数大于 500 个/μl。所有患者均接受 ledipasvir-sovaldi 每日一次，持续 6 周。主要疗效终点是治疗结束后 12 周持续病毒学应答率（SVR12）。本研究在 ClinicalTrials.gov 注册，编号为 NCT02457611。
结果
2015 年 6 月 11 日至 2016 年 1 月 8 日，我们入组并治疗了 26 例患者。所有患者（100%）均为男性，24 例（92%）为白人，25 例（96%）正在接受抗逆转录病毒治疗。19 例（73%）为基因型 1a，7 例（27%）为基因型 4 HCV。总体而言，26 例患者中有 20 例（77%；95%CI 56-91）达到 SVR12：19 例基因型 1a 中 15 例（79%），7 例基因型 4 中 5 例（71%）。6 例未达到 SVR12 的患者中，3 例复发，2 例治疗结束后 4 周持续病毒学应答但失访，1 例再感染。最常见的不良反应是疲劳（7 例[27%]）、鼻咽炎（7 例[27%]）和头痛（6 例[23%]）。没有患者因不良反应而停药或中断治疗。研究期间未发生 HIV 反弹。
结论
在 HIV-1 合并感染的急性基因型 1 或 4 HCV 感染患者中，使用 ledipasvir-sovaldi 的固定剂量联合治疗的治愈率与基于干扰素的治疗相似，但治疗持续时间更短，安全性更好。
资助
吉利德科学公司。
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