Pharmacokinetics of low-dose lopinavir/ritonavir tablet formulation in HIV-1 infected children

Abstract

Methods: This was an open-label, cross-over study of 24 HIV-infected children with HIV RNA < 50 copies/ml comparing PK parameter of standard dose LPV/r and low dose of LPV/r for 4 weeks. LPV dosage was prescribed by body weight band; 25~35 kg: LPV/r 300/75 vs. 200/50 mg, > 35 kg 400/100 vs. 300/75 mg. Glood samples were drawn at 0 (pre-dose), 2,4,6,8, 10 and 12 hours. Plasma concentrations of LPV and RTV were measured by HPLC method. The acceptable C12h is > 1 mg/L. The HIV RNA was measured at week 12 after switch back to standard dose for 4 weeks. Results: Twenty four children were included. Median (interquartile range) age, body weight, 3 CD4 count were 13.5 (12-15) years, 33.4 (28.3-41.1) kg, 913(737-1,178) ce"sl mrn . Geometric mean (95% Confidence I nterval) value with standard dose lopinavir AUCo.12 h' C max ,C 12h and T half were 93.8 (82.9-106.3) mg.h/L, 10.8(9.6-12.0) mg/L, 3.7(3.0-4.6) mg/L, and 4.8 (4.0-5.8) h respectively. For low dose LPV these values were 83.1 (72.2-95.6) mg .h/l, 10.7 (9.5-12.0) mg/L, 2.8 (2.1-3.6) mg/L, and 4.1 (3.5-4.8) h, respectively. In the multivariate analysis, there was no significant different in LPV AUC (p=0.35) and C12h (p=0.65) between standard and low dose LPV. But the AUC of ritonavir is the strong predictor for LPV AUC and C12h (p<0.001). One child (3%) had C12h < 1 mg/L (0.82 mg/L) but still had undetectable HIV RNA. There were 2 children had HIV RNA = 52 and 99 copies/ml but C12h >1 mg/L. Conclusions: Low dose of LPV/r provide adequate pharmacokinetic parameters. Successful usage of low dose LPV/r could have a significant public health impact in reducing side effects and costs related to treating complications and procuring the drug. A larger randomized clinical study to assess efficecy of low dose vs. standard dose of LPV/r among HIV-infected children should be explored.