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Title: Pharmacokinetics and safety profile of artesunate-amodiaquine coadministered with antiretroviral therapy in malaria-uninfected HIV-positive malawian adults
Authors: Clifford G. Banda
Fraction Dzinjalamala
Mavuto Mukaka
Jane Mallewa
Victor Maiden
Dianne J. Terlouw
David G. Lalloo
Saye H. Khoo
Victor Mwapasa
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
University of Malawi College of Medicine
Liverpool School of Tropical Medicine
University of Liverpool
Mahidol University
Centre for Tropical Medicine
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jul-2018
Citation: Antimicrobial Agents and Chemotherapy. Vol.62, No.7 (2018)
Abstract: Copyright © 2018 Banda et al. There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus-infected (HIV) 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 0–28 ) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria-uninfected adults (n 6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort (n 25/arm) received the full regimen. In step 1, there were no safety signals or significant differences in desethylamodiaquine AUC 0–28 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 0–28 , 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 (P 0.001). No significant differences in AUC 0–28 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]; P 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.
ISSN: 10986596
Appears in Collections:Scopus 2018

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