Gondrie Ivar P E, Bastiaans Diane E T, Fraaij Pieter L A, Driessen Gertjan J A, van der Knaap Linda C, Visser Eline G, van Jaarsveld Petronette, de Groot Ronald, Hartwig Nico G, Burger David M, van Rossum Annemarie M C
From the *Department of Pediatrics, Division of Infectious Diseases and Immunology, Erasmus MC University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; †Department of Pharmacy, and ‡Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; and §Department of Pediatrics, Franciscus Hospital, Rotterdam, The Netherlands.
Pediatr Infect Dis J. 2017 Oct;36(10):976-980. doi: 10.1097/INF.0000000000001627.
The use of lopinavir/ritonavir once-daily (LPV/r QD) has not been approved for children. Good short-term clinical, virologic and immunologic outcomes have been observed in children on LPV/r QD.
We evaluated the long-term effectiveness of a LPV/r QD containing regimen in HIV-1-infected children in clinical practice. Selected children (0-18 years of age) with an undetectable HIV-1 RNA viral load (<50 copies/mL) for at least 6 months on a twice-daily LPV/r-containing regimen switched to LPV/r QD. The main outcome measures were the percentage of patients with an undetectable HIV-1 viral load each subsequent year after switch to LPV/r QD (on treatment and last observation carried forward), and virologic failure during follow-up (>400 copies/mL twice within 6 months). Also, the exposure to LPV on the initial once-daily dosing regimen was determined.
Forty children (median age: 6.5 years; range: 1.0-17) were included. Median follow-up was 6.3 years (range: 1.0-10.3). During yearly follow-up, the percentage of children with an undetectable viral load varied between 82% and 100% (on treatment) and 83% and 93% (last observation carried forward). Five children (12.5%) met the criteria for failure. CD4+ and CD8+ counts remained stable at normal values. Geometric mean LPV area under the plasma concentration-time curve (linear up-log down method) over a dosing interval from time 0 to 24 hours after dosing was 169.3 mg x h/L, and last observed drug concentration was 1.35 mg/L. Adverse events were encountered in 8 patients, were mainly gastrointestinal, and in these cases, no reason to stop treatment.
A once-daily LPV/r-containing regimen in HIV-1-infected children with intensive clinical and therapeutic drug monitoring is well tolerated and has good long-term clinical, virologic and immunologic outcomes.
洛匹那韦/利托那韦每日一次（LPV/r QD）的用法尚未被批准用于儿童。在接受LPV/r QD治疗的儿童中观察到了良好的短期临床、病毒学和免疫学结果。
我们在临床实践中评估了含LPV/r QD方案对HIV-1感染儿童的长期有效性。选定的（0至18岁）儿童在每日两次含LPV/r的方案治疗下，HIV-1 RNA病毒载量至少6个月检测不到（<50拷贝/mL），然后改用LPV/r QD。主要结局指标为改用LPV/r QD后每年病毒载量检测不到的患者百分比（治疗中及末次观察向前结转），以及随访期间的病毒学失败情况（6个月内两次>400拷贝/mL）。此外，还测定了初始每日一次给药方案下的LPV暴露量。
纳入40名儿童（中位年龄：6.5岁；范围：1.0至17岁）。中位随访时间为6.3年（范围：1.0至10.3年）。在年度随访期间，病毒载量检测不到的儿童百分比在82%至100%（治疗中）和83%至93%（末次观察向前结转）之间变化。5名儿童（12.5%）符合失败标准。CD4+和CD8+细胞计数保持在正常水平稳定。给药后0至24小时给药间隔内血浆浓度-时间曲线下LPV的几何平均面积（线性上升-对数下降法）为169.3mg·h/L，末次观察到的药物浓度为1.35mg/L。8名患者出现不良事件，主要为胃肠道不良事件，在这些病例中，无停药理由。
在HIV-1感染儿童中，每日一次含LPV/r的方案在加强临床和治疗药物监测的情况下耐受性良好，具有良好的长期临床、病毒学和免疫学结果。
