Clifford G. BandaFraction DzinjalamalaMavuto MukakaJane MallewaVictor MaidenDianne J. TerlouwDavid G. LallooSaye H. KhooVictor MwapasaMalawi-Liverpool-Wellcome Trust Clinical Research ProgrammeUniversity of Malawi College of MedicineLiverpool School of Tropical MedicineUniversity of LiverpoolMahidol UniversityCentre for Tropical Medicine2019-08-232019-08-232018-08-01Antimicrobial Agents and Chemotherapy. Vol.62, No.8 (2018)10986596006648042-s2.0-85052020605https://repository.li.mahidol.ac.th/handle/123456789/46486Copyright © 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.)Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.00634-18