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

Abstract

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 200/50mg) is used for children weighing 25-34.9kg, 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 (3-15years), weighing 14-24.9kg received 200/50mg LPV/r orally twice daily; those weighing 25-34.9kg received 400/100mg LPV/r in the morning and 200/50mg in the evening; and those weighing ≥35kg received 400/100mg 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 (AUC0-12h) for LPV was 116.2h∗mg/L (coefficient of variation [CV%], 37%), comparable to children receiving WHO-recommended dosages. The GM trough concentration was 7.7mg/L (52%), 57% higher than the reference value of 4.9mg/L (95% confidence interval, 4.14-5.80), mainly caused by higher exposure in children 25-34.9kg. There were no differences in LPV AUC0-12hor Ctroughbetween backbones. Conclusions Children (3-15years), weighing ≥14kg 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 200/50mg in children 25-34.9kg.