An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment



Francis, Jose, Barnes, Karen I, Workman, Lesley, Kredo, Tamara, Vestergaard, Lasse S, Hoglund, Richard M, Byakika-Kibwika, Pauline, Lamorde, Mohammed, Walimbwa, Stephen I, Chijioke-Nwauche, Ifeyinwa
et al (show 11 more authors) (2020) An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 64 (5). e02394-e02319.

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Abstract

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

Item Type: Article
Uncontrolled Keywords: uncomplicated malaria, lumefantrine, human immunodeficiency virus, drug-drug interactions, population pharmacokinetics
Depositing User: Symplectic Admin
Date Deposited: 04 Mar 2020 08:28
Last Modified: 18 Jan 2023 23:59
DOI: 10.1128/AAC.02394-19
Open Access URL: https://aac.asm.org/content/early/2020/02/11/AAC.0...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3077614