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<jats:title>ABSTRACT</jats:title> <jats:p> There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus-infected (HIV <jats:sup>+</jats:sup> ) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared the area under the concentration-time curve from 0 to 28 days (AUC <jats:sub>0–28</jats:sub> ) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV <jats:sup>+</jats:sup> adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria-uninfected adults ( <jats:italic>n</jats:italic> = 6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort ( <jats:italic>n</jats:italic> = 25/arm) received the full regimen. In step 1, there were no safety signals or significant differences in desethylamodiaquine AUC <jats:sub>0–28</jats:sub> among participants in the ritonavir-boosted lopinavir, nevirapine, and antiretroviral therapy-naive arms. In step 2, compared with those in the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC <jats:sub>0–28</jats:sub> , with the following geometric means (95% confidence intervals [CIs]): 23,822 (17,458 to 32,506) versus 48,617 (40,787 to 57,950) ng · h/ml ( <jats:italic>P</jats:italic> &lt; 0.001). No significant differences in AUC <jats:sub>0–28</jats:sub> were observed between nevirapine and antiretroviral therapy-naive arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy-naive (0.0% [0/25]) arm (risk difference, 20% [95% CI, 4.3 to 35.7]; <jats:italic>P</jats:italic> = 0.018). The ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure, which may compromise artesunate-amodiaquine's efficacy. Coadministration of nevirapine and artesunate-amodiaquine may be associated with hepatoxicity. </jats:p>

Original publication





Antimicrobial Agents and Chemotherapy


American Society for Microbiology

Publication Date