Kamphuis, AEM;
Kiezebrink, T;
Waalewijn, H;
Bamford, A;
Szubert, AJ;
Chabala, C;
Bwakura-Dangarembizi, M;
... Burger, DM; + view all
(2025)
Pharmacokinetics of lopinavir/ritonavir in second-line treatment of children living with HIV in the CHAPAS-4 trial.
AIDS
10.1097/QAD.0000000000004328.
(In press).
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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 (AUC<inf>0-12h</inf>) 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 AUC<inf>0-12h</inf>or C<inf>trough</inf>between 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.
| Type: | Article |
|---|---|
| Title: | Pharmacokinetics of lopinavir/ritonavir in second-line treatment of children living with HIV in the CHAPAS-4 trial |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/QAD.0000000000004328 |
| Publisher version: | https://doi.org/10.1097/qad.0000000000004328 |
| Language: | English |
| Additional information: | This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article. If an article is Open Access and published under the Creative Commons Attribution License (CC BY) permission for reuse is not required. Before requesting permission, be sure to check the Copyright status of the source material and review which Creative Commons License applies to the publication, if any. |
| Keywords: | HIV, children, lopinavir/ritonavir, pharmacokinetics, second-line |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10214463 |
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