Abstract: A parallel study design investigated the pharmacokinetic parameters of lumefantrine in adults co-infected with malaria and HIV-1 in 2 groups enrolled prospectively: Antiretroviral Therapy (ART) naive patients and patients on Efavirenz (EFV)-based therapy. Both groups were on co-Trimoxazole (TS) prophylaxis. Both groups received Artemether-Lumefantrine (AL) combination twice daily for 3 days. Venous blood was collected just before last dose and subsequently at 2, 4, 8, 24 and 120 h post dose. Concentrations of lumefantrine were determined by high performance liquid chromatography. Mean area under the plasma concentration-time curve (AUC0-∞) was 264.8 (243.1-286.5) μg h mL-1, mean maximum Concentration (Cmax) was 4.05 (3.77-4.33) μg mL-1, mean day 7 Concentration (Cday 7) was 0.26 (0.20-0.32) μg mL-1, mean elimination rate (K0) was 0.020933 (0.020219-0.021647) μg h-1 and mean half life was (T1/2) 33.3 (30.9-35.7) h for subjects on EFV-based ART and for ART naive subjects were 375.2 (349.7-400.7) μg h mL-1, 6.08 (5.57-6.59) μg mL-1, 0.64 (0.54-0.74) μg mL-1, 0.0195 (0.0185-0.0205) μg h-1 and 36.0 (34.1-37.9) h, respectively. Time to maximum concentration (Tmax) was 4 h in both groups. EFV based ART significantly decreases the exposure of lumefantrine. AL is well tolerated in these subjects.