洛匹那韦/利托那韦低剂量在 HIV 感染儿童中的药代动力学和 48 周疗效。

Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children.

机构信息

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand.

出版信息

J Antimicrob Chemother. 2009 Nov;64(5):1080-6. doi: 10.1093/jac/dkp322. Epub 2009 Sep 2.

DOI:10.1093/jac/dkp322

PMID:19729375

Abstract

BACKGROUND

Lopinavir/ritonavir is a common protease inhibitor (PI) used for second-line regimens in children. Several studies have shown higher plasma concentrations of antiretroviral agents in Thai adults than in Caucasians, suggesting that lower doses may be used.

METHODS

An open label study in 24 HIV-infected children between the age of 2 and 18 years, naive to PIs, randomized to receive either the WHO-recommended dose of lopinavir/ritonavir or a low dose (70% of the standard dose) twice daily in combination with zidovudine and lamivudine. A 12 h pharmacokinetic study was done at 4-6 weeks after starting treatment. Treatment outcomes were evaluated at week 48. The clinical trial number of the study is NCT00887120.

RESULTS

The medians [interquartile ranges (IQRs)] of age, body surface area, percentage CD4 and plasma HIV RNA were 9.5 years (7.0-12.3), 0.9 m(2) (0.8-1.1), 17% (11%-24%) and 4.6 log(10) copies/mL (4.1-4.9), respectively. The median (IQR) lopinavir dose was 279 mg/m(2)/dose (263-294) and 194 mg/m(2)/dose (176-206) in the standard and low-dose arms, respectively. Median (IQR) AUC(0-12) and C(trough) of lopinavir were 117.6 mg.h/L (74.0-128.5) and 4.9 mg/L (2.7-8.0) for the standard arm and 83.8 mg.h/L (56.0-112.9) and 3.4 mg/L (2.7-5.4) for the low-dose arm. One child in the low-dose arm had a lopinavir pre-dose level of <1.0 mg/L. At week 48, the median percentage CD4 was 22% (15%-28%) and 27% (21%-31%) in the standard and low-dose arms, respectively, while 50% and 83% of children had HIV RNA <50 copies/mL, respectively (P = 0.19).

CONCLUSIONS

Low-dose lopinavir displayed adequate pharmacokinetic parameters and good efficacy as compared with standard-dose lopinavir in Thai children. A larger study to investigate the efficacy of low-dose lopinavir is warranted.

摘要

背景

洛匹那韦/利托那韦是一种常用于儿童二线治疗方案的常见蛋白酶抑制剂（PI）。多项研究表明，泰国成年人的抗逆转录病毒药物血浆浓度高于白种人，提示可能需要使用较低剂量。

方法

这是一项在 24 名年龄在 2 至 18 岁、未使用过 PI 的 HIV 感染儿童中进行的开放性标签研究，这些儿童随机接受世界卫生组织推荐剂量的洛匹那韦/利托那韦或低剂量（标准剂量的 70%），每日两次，联合齐多夫定和拉米夫定。在开始治疗后 4-6 周进行 12 小时药代动力学研究。在第 48 周评估治疗结果。该研究的临床试验编号为 NCT00887120。

结果

中位年龄[四分位间距（IQR）]、体表面积、CD4 百分比和血浆 HIV RNA 分别为 9.5 岁（7.0-12.3）、0.9 m²（0.8-1.1）、17%（11%-24%）和 4.6 log10 拷贝/ml（4.1-4.9）。标准剂量组和低剂量组洛匹那韦的中位（IQR）剂量分别为 279 mg/m²/剂量（263-294）和 194 mg/m²/剂量（176-206）。标准剂量组和低剂量组洛匹那韦的中位（IQR）AUC（0-12）和 C（谷）分别为 117.6 mg·h/L（74.0-128.5）和 4.9 mg/L（2.7-8.0）和 83.8 mg·h/L（56.0-112.9）和 3.4 mg/L（2.7-5.4）。低剂量组中有 1 名儿童洛匹那韦的预剂量水平<1.0 mg/L。第 48 周时，标准剂量组和低剂量组的中位 CD4 百分比分别为 22%（15%-28%）和 27%（21%-31%），而 50%和 83%的儿童 HIV RNA<50 拷贝/ml，分别（P = 0.19）。