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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46486
Title: Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine 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-Aug-2018
Citation: Antimicrobial Agents and Chemotherapy. Vol.62, No.8 (2018)
Abstract: Copyright © 2018 Banda et al. There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus-infected (HIV-positive [HIV]) individuals taking antiretroviral therapy (ART). In a two-step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared the area under the concentration-time curve from days 0 to 28 (AUC0–28 days) and the safety outcomes of piperaquine among malaria-uninfected HIV adults. In step 1, half the adult dose of DHA-PQ was administered for 3 days as an initial safety check to four groups (n 6/group) of HIV adults (age 18 years): (i) antiretroviral-naive individuals, (ii) individuals on nevirapine-based ART, (iii) individuals on efavirenz-based ART, and (iv) individuals on ritonavir-boosted lopinavir-based ART. In step 2, a full adult treatment course of DHA-PQ was administered to a different cohort of participants in three groups: (i) antiretroviral-naive individuals, (ii) individuals on efavirenz-based ART, and (iii) individuals on nevirapine-based ART (n 10 to 15/group). The ritonavir-boosted lopinavir-based ART group was dropped in step 2 due to the limited number of participants who were on this second-line ART and were eligible for recruitment. Piperaquine’s AUC0–28 days in both steps was 43% lower among participants on efavirenz-based ART than among ART-naive participants. There were no significant differences in AUC0–28 days between the other ART groups and the ART-naive group in each of the two steps. Furthermore, no differences in treatment-emergent clinical and laboratory adverse events were observed across the groups in steps 1 and 2. Although it was well tolerated at the half and full standard adult treatment courses, the efavirenz-based antiretroviral regimen was associated with reduced piperaquine exposure, which may compromise dihydroartemisinin-piperaquine’s effectiveness in programmatic settings. (The clinical trials presented in this study have been registered at the WHO’s International Clinical Trials Registry Platform under ID numbers PACTR2010030001871293 and PACTR2010030001971409.)
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052020605&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46486
ISSN: 10986596
00664804
Appears in Collections:Scopus 2018

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