Pharmacokinetics of lopinavir/ritonavir in second-line treatment of children living with HIV in the CHAPAS-4 trial.

IF 3.1 2区医学 Q3 IMMUNOLOGY

AIDS Pub Date : 2025-08-26 DOI:10.1097/QAD.0000000000004328

Anne E M Kamphuis, Timo Kiezebrink, Hylke Waalewijn, Alasdair Bamford, Alexander J Szubert, Chishala Chabala, Mutsa Bwakura-Dangarembizi, Shafic Makumbi, Joan Nangiya, Vivian Mumbiro, Veronica Mulenga, Victor Musiime, Saskia N de Wildt, Angela P H Colbers, Diana M Gibb, David M Burger

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引用次数: 0

Abstract

Objective: Lopinavir/ritonavir (LPV/r) remains a much-used drug combination for treatment of children with HIV, but pharmacokinetic data when the adult formulation (LPV/r 200/50 mg) is used for children weighing 25-34.9 kg, or when combined with tenofovir alafenamide/emtricitabine (TAF/FTC), is currently lacking.

Design: We aim to provide this data by an intensive LPV/r pharmacokinetic sub-study nested within the CHAPAS-4 trial (#ISRCTN22964075).

Methods: Children (3-15 years), weighing 14-24.9 kg received 200/50 mg LPV/r orally twice daily; those weighing 25-34.9 kg received 400/100 mg LPV/r in the morning and 200/50 mg in the evening; and those weighing ≥35 kg received 400/100 mg LPV/r twice daily. LPV/r was used in combination with either TAF/FTC or standard-of-care backbone (abacavir/lamivudine or zidovudine/lamivudine). Pharmacokinetic parameters were compared to those reported in children receiving WHO-recommended dosages.

Results: We enrolled 40 children from Uganda, Zambia and Zimbabwe. The geometric mean (GM) area under the concentration-time curve (AUC 0-12h ) for LPV was 116.2 h∗mg/L (coefficient of variation [CV%], 37%), comparable to children receiving WHO-recommended dosages. The GM trough concentration was 7.7 mg/L (52%), 57% higher than the reference value of 4.9 mg/L (95% confidence interval, 4.14-5.80), mainly caused by higher exposure in children 25-34.9 kg. There were no differences in LPV AUC 0-12h or C trough between backbones.

Conclusions: Children (3-15 years), weighing ≥14 kg and taking LPV/r in second-line treatment achieve adequate exposure of LPV within limits reported to be safe and well tolerated. These data support the use of a LPV/r based regimen and the adult formulation of 200/50 mg in children 25-34.9 kg.

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CHAPAS-4试验中洛匹那韦/利托那韦二线治疗HIV儿童的药代动力学

目的：洛匹那韦/利托那韦（LPV/r）仍然是治疗儿童HIV的常用药物组合，但目前缺乏成人配方（LPV/r 200/50 mg）用于体重25-34.9 kg的儿童，或与替诺福韦alafenamide/恩曲他滨（TAF/FTC）联合使用的药代动力学数据。设计：我们的目标是通过CHAPAS-4试验（#ISRCTN22964075）中密集的LPV/r药代动力学亚研究提供这些数据。方法：儿童（3-15岁），体重14-24.9 kg，口服LPV/r 200/50 mg，每日2次；体重25 ~ 34.9 kg的患者，早上给予400/100 mg LPV/r，晚上给予200/50 mg LPV/r；体重≥35 kg者给予400/100 mg LPV/r，每日2次。LPV/r与TAF/FTC或标准护理骨干（阿巴卡韦/拉米夫定或齐多夫定/拉米夫定）联合使用。将药代动力学参数与接受世卫组织推荐剂量的儿童报告的药代动力学参数进行比较。结果：我们招募了40名来自乌干达、赞比亚和津巴布韦的儿童。LPV在浓度-时间曲线下的几何平均（GM）面积（AUC 0-12h）为116.2 h∗mg/L（变异系数[CV%]， 37%），与接受世卫组织推荐剂量的儿童相当。GM谷浓度为7.7 mg/L(52%)，比参考值4.9 mg/L高出57%(95%可信区间4.14 ~ 5.80)，主要原因是25 ~ 34.9 kg的儿童暴露量较高。LPV、AUC 0 ~ 12h、C槽在各骨干间无差异。结论：儿童（3-15岁），体重≥14 kg，在二线治疗中服用LPV/r，在安全且耐受性良好的范围内获得足够的LPV暴露。这些数据支持使用LPV/r为基础的方案和成人配方200/50毫克25-34.9公斤的儿童。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

AIDS 医学-病毒学

CiteScore

5.90

自引率

5.30%

发文量

478

审稿时长

3 months

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