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 m2 (0.8–1.1), 17% (11%–24%) and 4.6 log10 copies/mL (4.1–4.9), respectively. The median (IQR) lopinavir dose was 279 mg/m2/dose (263–294) and 194 mg/m2/dose (176–206) in the standard and low-dose arms, respectively. Median (IQR) AUC0–12 and Ctrough 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.

ปี 2552, November ปีที่: 64 ฉบับที่ 5 หน้า 1080-1086

Protease inhibitors, Second-line treatment, Therapeutic drug monitoring