Pharmacokinetics of lopinavir/ritonavir in HIV-infected children in Africa according to WHO weight band dosage regimen

Abstract

Background Availability of HIV treatment remains low in children in Africa. Lopinavir/ritonavir (LPV/r), combined with a backbone of two NRTIs, is a widely used drug combination in treating HIV worldwide. CHAPAS4 is a randomized clinical trial studying second-line treatment options for children with HIV. In this paper, we present the results of a nested PK sub study within CHAPAS-4 to investigate LPV/r PK parameters combined with different NRTI-backbones using a WHO weight band dosing regimen.

Method Patients in this sub study were randomized to LPV/r, as well as one of three NRTI-backbones. Children received a dose based on WHO weight band standards. Generic LPV/r tablets were used in this study. PK sampling was done in steady state conditions and a sample was taken at t=0, 1, 2, 4, 6, 8 and 12 hours after supervised intake with a standardized breakfast. The minimal effective LPV concentration was determined on 1.0 mg/L. Our aim was to compare LPV/r PK parameters among different NRTIbackbone and weight band groups. A second aim was to study whether the children received sufficient LPV plasma concentrations.

Results We had 41 eligible LPV and RTV PK profiles in this PK sub study. The GM (CV%) LPV AUC0-12h was 116,9 mg/L (36,0%). The LPV GM (CV%) LPV Ctrough was 7.6 mg/L (50.2%). No statistical significant LPV PK parameters differences were found between the different NRTI-backbone groups. No children had Ctrough concentrations below the minimal effective LPV concentration.

Conclusions This nested sub study within CHAPAS-4 shows that current WHO weight band dosing and generic LPV tablets deliver sufficient LPV plasma concentrations in second-line HIV therapy in African children. Furthermore, we found no difference in LPV/r plasma concentrations between different NRTIbackbones, meaning LPV/r can be used safely besides TAF/FTC.