JAC Advance Access originally published online on September 2, 2009
Journal of Antimicrobial Chemotherapy 2009 64(5):1080-1086; doi:10.1093/jac/dkp322
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Original research |
Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children
1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand 2 Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 3 International Antiretroviral Trial Evaluation Centre, Amsterdam, The Netherlands 4 South East Asia Research Collaboration with University of Hawaii (SEARCH), Bangkok, Thailand 5 Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 6 Division of Allergy and Clinical Immunology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
Received 18 June 2009; returned 25 July 2009; revised 29 July 2009; accepted 3 August 2009
* Corresponding author. Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Tel: +66-2-255-7335; Fax: +66-2-252-5779; E-mail: thanyawee.p{at}hivnat.org
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 [ClinicalTrials.gov] .
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.
Keywords: second-line treatment , therapeutic drug monitoring , protease inhibitors
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  M. N. Neely and N. Y. Rakhmanina Comment on: Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children J. Antimicrob. Chemother., January 19, 2010; (2010) dkp489v1. [Full Text] [PDF]
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