Extended Duration Artemether-lumefantrine Treatment for Malaria in Children
Summary
This project determines the pharmacokinetic/pharmacodynamic (PK/PD) of an extended artemether-lumefantrine (AL) dosing regimen in HIV-infected children on efavirenz (EFV)-based antiretroviral therapy (ART) that is designed to improve the PK exposure and treatment efficacy of this artemisinins-based combination therapy (ACT) regimen. Our overarching goal is to inform the best treatment guidelines for young children in Africa. HIV-infected and HIV-uninfected children were enrolled for intensive PK studies, as well as additional children for population PK studies to enhance association analyses with clinical outcomes.
Timeline
- Start
- 2018-02-21
- Primary completion
- 2021-08-31
- Completion
- 2021-08-31
Outcome
Mixed primary results
paper Terminal median lumefantrine concentrations were significantly increased in the 5-day versus 3-day regimen on days 7, 14, and 21 (P < .001). PMID 36130191 ↗
paper Kaplan-Meier estimated 28-day (51% vs 40%) and 42-day risk (75% vs 68%) did not significantly differ between 3- and 5-day regimens. PMID 36130191 ↗
Publications
- Results Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Wang K, Li F, Mwebaza N, Aweeka FT, Parikh S. The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial. Clin Infect Dis. 2023 Feb 8;76(3):443-452. doi: 10.1093/cid/ciac783.
- Results Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Hoffmann TJ, Aweeka FT, Parikh S, Mwebaza N. Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial. J Clin Pharmacol. 2025 Jul;65(7):909-922. doi: 10.1002/jcph.6193. Epub 2025 Jan 24.
- Goodwin J, Kajubi R, Wang K, Li F, Wade M, Orukan F, Huang L, Whalen M, Aweeka FT, Mwebaza N, Parikh S. Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children. Nat Commun. 2024 May 7;15(1):3817. doi: 10.1038/s41467-024-48210-7.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Artemether | Small molecule | 20 mg | — |
| Subject | Artemether | Small molecule | 40 mg | — |
| Subject | Artemether | Small molecule | 60 mg | — |
| Subject | Artemether | Small molecule | 80 mg | — |
| Subject | lumefantrine | Small molecule | 120 mg | — |
| Subject | lumefantrine | Small molecule | 240 mg | — |
| Subject | lumefantrine | Small molecule | 360 mg | — |
| Subject | lumefantrine | Small molecule | 480 mg | — |