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Malaria Research and Treatment
Volume 2011, Article ID 703730, 5 pages
http://dx.doi.org/10.4061/2011/703730
Review Article

Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

1Infectious Diseases Institute and Infectious Diseases Network for Treatment and Research in Africa (INTERACT), Makerere University College of Health Sciences, P.O. Box 7061, Kampala, Uganda
2Department of Pharmacology and Therapeutics, Trinity College Dublin 2, Ireland
3Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX, UK
4International Health, Epidemiology en Social Medicine, Universiteit Antwerpen, Universiteitsplein 1, 2610 Antwerp, Belgium

Received 14 December 2010; Accepted 14 February 2011

Academic Editor: Neena Valecha

Copyright © 2011 Pauline Byakika-Kibwika et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemether-lumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.