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Title: An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment
Authors: Jose Francis
Karen I. Barnes
Lesley Workman
Tamara Kredo
Lasse S. Vestergaard
Richard M. Hoglund
Pauline Byakika-Kibwika
Mohammed Lamorde
Stephen I. Walimbwa
Ifeyinwa Chijioke-Nwauche
Colin J. Sutherland
Concepta Merry
Kimberley K. Scarsi
Nyagonde Nyagonde
Martha M. Lemnge
Saye H. Khoo
Ib C. Bygbjerg
Sunil Parikh
Francesca T. Aweeka
Joel Tarning
Paolo Denti
Makerere University
National Institute For Medical Research Tanzania
London School of Hygiene & Tropical Medicine
Københavns Universitet
University of Port Harcourt
South African Medical Research Council
Statens Serum Institut
University of California, San Francisco
University of Liverpool
University of Nebraska Medical Center
Mahidol University
Trinity College Dublin
Nuffield Department of Clinical Medicine
Yale University
University of Cape Town
4Muheza District Hospital
Asia Regional Centre
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-May-2020
Citation: Antimicrobial Agents and Chemotherapy. Vol.64, No.5 (2020)
Abstract: Copyright © 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.
ISSN: 10986596
Appears in Collections:Scopus 2020

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