患有血液系统恶性肿瘤和慢性丙型肝炎病毒（HCV）感染的儿童由于多次肝炎发作和化疗中断，肝病快速进展和恶性肿瘤复发的风险较高。因此，它们是微量消除丙型肝炎病毒感染的潜在候选者。本研究旨在评估急性淋巴细胞白血病 (ALL) 对直接作用抗病毒药物雷迪帕韦/索磷布韦 (LDV/SOF) 和 SOF 主要代谢物 GS-331007 的药代动力学 (PK) 特征的影响。这是一项 24-为期 12 周的前瞻性、对照、开放标签、2 组 PK 研究，患者每天口服 45/200 mg LDV/SOF 一次。符合条件的患者是 HCV-RNA 阳性、未接受治疗的儿童，年龄为 6 岁至 <12 岁和/或体重 17 至 <35 kg，患有基因型 4 慢性 HCV 感染，无肝硬化。主要疗效和安全性终点是所有患者均获得持续病毒学应答，且没有任何导致永久停用研究药物的不良事件。进行稳态非房室分析以确定 SOF、GS-331007 和 LDV 的 PK 参数作为主要 PK 结果。剂量适宜性基于与成人相比，暴露几何平均比率百分比在 50% 至 200% 范围内的 90% CI。 纳入 10 名 HCV 感染的 ALL 儿童（化疗治疗组）和 12 名符合条件的无恶性肿瘤儿童（对照组）并完成了学习期。所有 22 名患者均获得了持续的病毒学应答，没有出​​现导致研究药物中断或永久停用的不良事件。与对照组相比，ALL组患者的SOF、GS-331007和LDV暴露量相似。与成人相比，ALL 组中 GS-331007 的 AUCτ 较低，SOF 的 AUCτ 和 Cmax,ss 以及 LDV 的 Cmax,ss 稍高（接受限，50%-200%）。然而，观察到的疗效和良好的安全性使这些变化不具有临床意义。基于体重的 LDV/SOF (45/200 mg) 剂量对于体重 17 至 <35 kg 且经诊断的基因型 4 HCV 感染儿童非常有效且安全接受维持化疗的 ALL。患有和不患有血液恶性肿瘤的患者之间药物暴露、疗效和安全性临床终点的相似性支持了它们的治疗等效性。可能需要进行更大样本量的进一步研究，以确认 LDV/SOF 在 ALL 患者中的安全性，并在需要时建议血液恶性肿瘤儿童的适当剂量。gov 标识符：NCT03903185。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007.This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults.Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant.Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed.gov identifier: NCT03903185.Copyright © 2023 Elsevier Inc. All rights reserved.