Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults

Abstract EN

Background.

Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity.

We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics.

Methods.

We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10) and ART-naive controls (n=11).

Artesunate-amodiaquine 200/600 mg was given daily for three days.

Measurement of drug concentrations occurred between 0 and 96 hours after the final dose.

Pharmacokinetic parameters were determined using noncompartmental analysis.

Results.

Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03), resulting in a 45% increase in the AUC0-96 (105 versus 69 ug∗hr/L; P=0.02).

The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged.

A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC0-96=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008).

Conclusion.

Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.