Pediatr Infect Dis J. 2018 Feb;37(2):e29-e35. doi: 10.1097/INF.0000000000001817.
The World Health Organization (WHO) recommends weight band dosing of antiretrovirals for children. Data are limited describing drug exposure/safety of lopinavir/ritonavir using WHO weight band dosing.
International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1083 was a phase II/III trial assessing the pharmacokinetics (PK) and short-term safety, tolerance and efficacy of lopinavir/ritonavir in human immunodeficiency virus-infected children 3-25 kg dosed according to WHO weight bands, with liquid solution or meltrex extrusion tablets. The main PK target was an area under the curve (AUC0-24) of 80-320 μg·h/mL.
Of 97 enrolled participants, median age 2.5 years, 89 (91.8%) completed the protocol. Median LPV dose was 303 mg/m. The geometric mean (90% confidence limits) LPV PK AUC0-24 was 196 (177-217) μg·h/mL and Cmin was 2.47 (1.52-4.02) μg/mL. AUC0-24 was within the target range for 79% of participants. The median (Q1, Q3) difference between individual observed PK parameters and those expected if Food and Drug Administration dosing guidelines were followed was 30.7 (7.9, 54.3) for AUC0-24 and 0.56 (0, 1.27) for Cmin. Ten (10%) participants had grade 3 or 4 events deemed related to study treatment, mostly asymptomatic laboratory abnormalities. Three participants died of unrelated study treatment causes. At week 24, 57 of 79 (72%) participants reached viral suppression and the median increase in CD4% (n = 83) was 6.0 (P < 0.0001).
WHO weight band dosing guidelines in children achieved adequate LPV plasma exposure but was higher than that expected with Food and Drug Administration dosing guidelines. Despite the higher LPV exposure, the treatment was well tolerated and the 24-week efficacy data were favorable.
世界卫生组织（WHO）推荐采用体重区间剂量法给儿童服用抗逆转录病毒药物。目前，关于使用 WHO 体重区间剂量法给予洛匹那韦/利托那韦，描述其药物暴露/安全性的数据十分有限。
国际母婴儿科艾滋病临床试验组织（IMPAACT）P1083 是一项评估体重为 3-25kg 的人类免疫缺陷病毒（HIV）感染儿童接受洛匹那韦/利托那韦（根据 WHO 体重区间以口服液或熔融挤出片剂形式给药）药代动力学（PK）和短期安全性、耐受性及疗效的 II/III 期试验。主要 PK 目标为 80-320μg·h/mL 的曲线下面积（AUC0-24）。
97 名入组的参与者中，中位年龄为 2.5 岁，89 名（91.8%）完成了方案。中位 LPV 剂量为 303mg/m。洛匹那韦 PK AUC0-24 的几何均数（90%置信区间）为 196（177-217）μg·h/mL，Cmin 为 2.47（1.52-4.02）μg/mL。79%的参与者 AUC0-24 在目标范围内。如果遵循美国食品药品监督管理局（FDA）剂量指南，个体观察 PK 参数与预期值之间的中位数（Q1，Q3）差异为 AUC0-24 为 30.7（7.9，54.3），Cmin 为 0.56（0，1.27）。10 名（10%）参与者出现了 3 或 4 级与研究治疗相关的事件，大多为无症状的实验室异常。3 名参与者死于与研究治疗无关的原因。24 周时，79 名参与者中有 57 名（72%）达到病毒抑制，83 名参与者的 CD4%中位数增加了 6.0（P<0.0001）。
儿童采用 WHO 体重区间剂量法能达到足够的 LPV 血浆暴露，但高于 FDA 剂量指南的预期值。尽管 LPV 暴露较高，但治疗耐受性良好，24 周的疗效数据良好。
