An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.
Antimicrob Agents Chemother
; 64(5)2020 04 21.
Article
em En
| MEDLINE
| ID: mdl-32071050
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fármacos Anti-HIV
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Terapia Antirretroviral de Alta Atividade
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Lumefantrina
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Antimaláricos
Tipo de estudo:
Health_economic_evaluation
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Prognostic_studies
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Systematic_reviews
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article