Interactions between nevirapine and antimalarials (artemether and lumefantrine)

Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV respectively in Africa.

However, there is the potential for drug interactions with this combination as artemether and lumefantrine are substrates of CYP3A4 and nevirapine is both a substrate and inducer of CYP3A4.

This parallel-design pharmacokinetic study, obtained concentration-time profiles for lumefantrine, artemether, dihydroartemisinin and nevirapine in two groups of HIV-infected patients: ART-naïve and those stable on nevirapine-based therapy. Both groups (n=18 per group) received the recommended artemether-lumefantrine dose (80/480 mg). The primary outcome was day-7 lumefantrine concentrations, as these are associated with therapeutic response in malaria.

Nevirapine decreased artemether (p<0.0001) and dihydroartemisinin (p=0.01) AUC, but unexpectedly increased lumefantrine exposure. Median (range) day 7 lumefantrine concentrations were 622 ng/mL (185-2040) and 336 ng/mL (29-934) in the nevirapine and ART-naïve groups, respectively (p=0.0002). In the ART-naïve group, 6/18 subjects had day 7 lumefantrine concentrations below target (280 ng/ml) compared with 1/18 in the nevirapine group (Odds Ratio=8.5, 95%CI 0.9 to 80.02, p=0.061). Adverse events were similar between groups, with no difference in electrocardiographic QTcF and PR intervals.

The mechanism of inhibition of lumefantrine remains to be elucidated. Studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.

Kredo T et al. The interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1 infected patients. Antimicrob Agents Chemother, 2011, 55(12): 5616-5323.