Background Coadministration of artemether–lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults. Method A standard 3-day regimen of artemether–lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration–time data. Genotyping data were tested for compliance with Hardy–Weinberg equilibrium by Chi-square test. Linear regressions, Mann–Whitney U-test or Kruskal–Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22. Results Among a total of 69 malaria–HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27–36.5) years and body wei