Plasma concentrations of the HIV-protease inhibitor lopinavir are suboptimal in children aged 2 years and below

Abstract

Background: Lopinavir/ritonavir (LPV/r) has been licensed for the treatment of HIV-infected children >6 months in the US and >2 years in the EU. Limited LPV paediatric pharmacokinetic data are available. We studied LPV pharmacokinetics to determine whether the recommended dose (230/57.5 mg/m2 twice daily) results in optimal LPV exposure in all age groups. Virological efficacy was a secondary objective.

Methods: HIV-1-infected children who started treatment with LPV/r and two nucleoside reverse transcriptase inhibitors underwent a 12-h pharmacokinetic curve. LPV plasma concentrations were determined with a validated HPLC method with UV detection. If Cmin was <1.0 mg/l LPV/r dose was increased by 33%. Plasma trough levels were drawn subsequently. HIV-1 RNA was followed-up until week 48.

Results: A total of 23 children were included (seven girls; 16 boys), with a median (range) age of 5.6 (0.4-13.2) years. Mean (+/-SD) AUC0-12h, Cmax and Cmin of LPV were 75.3 (+/-33.7) mg/l.h, 9.33 (+/-3.27) mg/l and 3.68 (+/-2.48) mg/l, respectively, which is similar to previously published data. Interindividual variability was large. Cmin was inadequate in 7/23 children. Significantly more children <2 years had inadequate Cmin compared with children >2 years. Dose increase to +/-300/75 mg/m2 LPV/r led to Cmin >1.0 mg/l. The studied regimen provided excellent viral suppression for naive and pretreated patients.

Conclusions: Mean LPV pharmacokinetic parameters in these HIV-infected children are similar to published data, but exposure is significantly reduced in children <2 years. Prospective pharmacokinetic studies using 300/75 mg/m2 LPV/r in this age population are urgently warranted.