Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children.
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.
Puthanakit
Thanyawee
T
HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand. thanyawee.p@hivnat.org
van der Lugt
Jasper
J
Bunupuradah
Torsak
T
Ananworanich
Jintanat
J
Gorowara
Meena
M
Phasomsap
Chayapa
C
Jupimai
Thidarat
T
Boonrak
Pitch
P
Pancharoen
Chitsanu
C
Burger
David
D
Ruxrungtham
Kiat
K
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D010949:Plasma / Q000737:chemistry; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir