HIV infection and malaria can be epidemic in the same populations and may need to be treated simultaneously. Understanding potential interactions between antiretrovirals and antimalarials is critical to ensuring proper treatment.
Etravirine is a substrate and inducer of the CYP3A metabolizing enzyme and a substrate and inducer of CYP2C9 and CYP2C19. Darunavir and ritonavir are substrates and inducers of CYP3A. The antimalarials artemether and lumefantrine are mainly metabolized by CYP3A. Artemether is also partly metabolized by CYP2B6, CYP2C9, and CYP2C19. Dihydroartemisinin is the active metabolite of artemether.
Researchers from Janssen, maker of the nonnucleoside etravirine and the protease inhibitor darunavir, tested those two antiretrovirals in a randomized, two-way crossover study involving healthy volunteers without HIV infection or malaria. In one set of tests 17 volunteers took treatments A and B in random order with a 4-week washout period between the two treatments. Treatment A consisted of the antimalarials artemether and lumefantrine alone at a dose of 80/480 mg for 3 days. Treatment B consisted of etravirine at a dose of 200 mg twice daily for 21 days with 80/480 mg of artemether/lumefantrine for 3 days from day 8. In the second set of tests 16 healthy volunteers received two treatments in the sequence described for the first set of tests but with darunavir/ritonavir at a dose of 600/100 mg twice daily instead of etravirine.
