Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults

Background: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of arte-mether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/ lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. Methods: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/ 100 mgof lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac func-tion monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured. Results: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (Cmax) and area under the concentration–time curve (AUC) [median (range): 11