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dc.contributor.authorJose Francisen_US
dc.contributor.authorKaren I. Barnesen_US
dc.contributor.authorLesley Workmanen_US
dc.contributor.authorTamara Kredoen_US
dc.contributor.authorLasse S. Vestergaarden_US
dc.contributor.authorRichard M. Hoglunden_US
dc.contributor.authorPauline Byakika-Kibwikaen_US
dc.contributor.authorMohammed Lamordeen_US
dc.contributor.authorStephen I. Walimbwaen_US
dc.contributor.authorIfeyinwa Chijioke-Nwaucheen_US
dc.contributor.authorColin J. Sutherlanden_US
dc.contributor.authorConcepta Merryen_US
dc.contributor.authorKimberley K. Scarsien_US
dc.contributor.authorNyagonde Nyagondeen_US
dc.contributor.authorMartha M. Lemngeen_US
dc.contributor.authorSaye H. Khooen_US
dc.contributor.authorIb C. Bygbjergen_US
dc.contributor.authorSunil Parikhen_US
dc.contributor.authorFrancesca T. Aweekaen_US
dc.contributor.authorJoel Tarningen_US
dc.contributor.authorPaolo Dentien_US
dc.contributor.otherMakerere Universityen_US
dc.contributor.otherNational Institute For Medical Research Tanzaniaen_US
dc.contributor.otherLondon School of Hygiene & Tropical Medicineen_US
dc.contributor.otherKøbenhavns Universiteten_US
dc.contributor.otherUniversity of Port Harcourten_US
dc.contributor.otherSouth African Medical Research Councilen_US
dc.contributor.otherStatens Serum Instituten_US
dc.contributor.otherUniversity of California, San Franciscoen_US
dc.contributor.otherUniversity of Liverpoolen_US
dc.contributor.otherUniversity of Nebraska Medical Centeren_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherTrinity College Dublinen_US
dc.contributor.otherNuffield Department of Clinical Medicineen_US
dc.contributor.otherYale Universityen_US
dc.contributor.otherUniversity of Cape Townen_US
dc.contributor.other4Muheza District Hospitalen_US
dc.contributor.otherAsia Regional Centreen_US
dc.identifier.citationAntimicrobial Agents and Chemotherapy. Vol.64, No.5 (2020)en_US
dc.description.abstractCopyright © 2020 Francis et al. 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 lopinavirritonavir- based antiretroviral therapy (ART), while it decreased by 47% with efavirenzbased 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.en_US
dc.rightsMahidol Universityen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleAn individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatmenten_US
Appears in Collections:Scopus 2020

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