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

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. oadministration 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

Safety and efficacy of lumefantrine-artemether (Coartem(R)) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults

Background In Zambia; unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria. Although the safety and efficacy of AL have been extensively documented; no clinical trials had been carried out in Zambia. Methods Nine hundred seventy one adult patients with uncomplicated malaria were randomized to either sulfadoxine-pyrimethamine (SP)(486) or AL (485) and followed up for 45 days. Outcome of treatment was defined according to the standard WHO classification. Recurrent parasitaemia were genotyped to distinguish between recrudescence and new infection. Results Fever at day 3 was significantly lower (AL: 0.9; 4/455; SP: 3;5; 15/433; p = 0.007) and the mean haemoglobin at day 45 significantly higher (AL: 134 g/l; SP 130g/l; p = 0.02) in the AL group. Almost all clinical symptoms cleared faster with AL. Early treatment failure was significantly higher in the SP (25/464) than in the AL (2/463) (OR: 13.1 95CI: 3.08-55.50; P0.001). The rate of new infections was similar in both groups (18 with SP and 19 with AL). Late clinical failure (OR: 2.55; 95CI: 1.34-4.84; P