Publication: Pharmacokinetics and safety profile of artesunate-amodiaquine coadministered with antiretroviral therapy in malaria-uninfected HIV-positive malawian adults
Issued Date
2018-07-01
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ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85049015219
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.62, No.7 (2018)
Suggested Citation
Clifford G. Banda, Fraction Dzinjalamala, Mavuto Mukaka, Jane Mallewa, Victor Maiden, Dianne J. Terlouw, David G. Lalloo, Saye H. Khoo, Victor Mwapasa Pharmacokinetics and safety profile of artesunate-amodiaquine coadministered with antiretroviral therapy in malaria-uninfected HIV-positive malawian adults. Antimicrobial Agents and Chemotherapy. Vol.62, No.7 (2018). doi:10.1128/AAC.00412-18 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46574
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Title
Pharmacokinetics and safety profile of artesunate-amodiaquine coadministered with antiretroviral therapy in malaria-uninfected HIV-positive malawian adults
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.