Pharmacokinetics of lopinavir/ritonavir in second-line treatment of children living with HIV in the CHAPAS-4 trial

Objective: Lopinavir/ritonavir (LPV/r) remains a much-used drug combination for treatment of children with HIV, but pharmacokinetic data when the adult formulation (LPV/r 200/50 mg) is used for children weighing 25–34.9 kg, or when combined with tenofovir alafenamide/emtricitabine (TAF/FTC), is currently lacking. Design: We aim to provide this data by an intensive LPV/r pharmacokinetic sub-study nested within the CHAPAS-4 trial (#ISRCTN22964075). Methods: Children (3–15 years), weighing 14–24.9 kg received 200/50 mg LPV/r orally twice daily; those weighing 25–34.9 kg received 400/100 mg LPV/r in the morning and 200/50 mg in the evening; and those weighing ≥35 kg received 400/100 mg LPV/r twice daily. LPV/r was used in combination with either TAF/FTC or standard-of-care backbone (abacavir/lamivudine or zidovudine/lamivudine). Pharmacokinetic parameters were compared to those reported in children receiving WHO-recommended dosages. Results: We enrolled 40 children from Uganda, Zambia and Zimbabwe. The geometric mean (GM) area under the concentration-time curve (AUC 0–12h ) for LPV was 116.2 h∗mg/L (coefficient of variation [CV%], 37%), comparable to children receiving WHO-recommended dosages. The GM trough concentration was 7.7 mg/L (52%), 57% higher than the reference value of 4.9 mg/L (95% confidence interval, 4.14–5.80), mainly caused by higher exposure in children 25–34.9 kg. There were no differences in LPV AUC 0–12h or C trough between backbones. Conclusions Children (3–15 years), weighing ≥14 kg and taking LPV/r in second-line treatment achieve adequate exposure of LPV within limits reported to be safe and well tolerated. These data support the use of a LPV/r based regimen and the adult formulation of 200/50 mg in children 25–34.9 kg.