%0 Journal Article %T Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals %A Pauline Byakika-Kibwika %A Mohammed Lamorde %A Harriet Mayanja-Kizza %A Saye Khoo %A Concepta Merry %A Jean-Pierre Van geertruyden %J Malaria Research and Treatment %D 2011 %I Hindawi Publishing Corporation %R 10.4061/2011/703730 %X 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. 1. Introduction Human immunodeficiency virus (HIV) and malaria have overlapping geographical distribution. Together, the two diseases account for 4 million deaths a year worldwide [1]. Over 90% of the world malaria burden occurs in sub-Saharan Africa, the region with 67% of the global HIV burden. Given the extensive overlap in geographical distribution of the two diseases, any interaction between the two could have profound public health consequences. In areas with stable malaria transmission, HIV increases risk of malaria infection and clinical malaria especially in individuals with advanced immunosuppression and in areas with unstable malaria transmission; HIV-infected individuals are at increased risk for severe malaria and death [1, 2]. This vulnerable population requires prompt, safe and effective antimalarial treatment. Current guidelines for malaria treatment advocate use of artemisinin-based combination therapies (ACTs). Treatment of malaria in HIV-infected individuals receiving ART poses significant challenges with gaps in the knowledge of ART and ACT drug-drug interactions and their consequences. Antiretroviral drugs are among the most therapeutically risky drugs for drug-drug interactions due to the potent inhibition and induction of cytochrome (CYP) enzymes as well as transport proteins. The combination of at least three drugs for highly active ART increases the risk for drug-drug interactions. The %U http://www.hindawi.com/journals/mrt/2011/703730/