Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.



Banda, Clifford G ORCID: 0000-0002-0757-5259, Dzinjalamala, Fraction, Mukaka, Mavuto, Mallewa, Jane, Maiden, Victor, Terlouw, Dianne J ORCID: 0000-0001-5327-8995, Lalloo, David G ORCID: 0000-0001-7680-2200, Khoo, Saye H and Mwapasa, Victor ORCID: 0000-0002-2748-8902
(2018) Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults. Antimicrobial agents and chemotherapy, 62 (8).

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Abstract

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.).

Item Type: Article
Uncontrolled Keywords: Humans, HIV Infections, Malaria, Artemisinins, Benzoxazines, Nevirapine, Quinolines, Antimalarials, Anti-Retroviral Agents, Adult, Middle Aged, Female, Male
Depositing User: Symplectic Admin
Date Deposited: 31 May 2019 10:29
Last Modified: 15 Jan 2021 01:11
DOI: 10.1128/aac.00634-18
Open Access URL: http://doi.org/10.1128/AAC.00634-18
URI: https://livrepository.liverpool.ac.uk/id/eprint/3043831