Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults

Banda, C; Dzinjalamala, F; Mukaka, M; Mallewa, J; Maiden, V; Terlouw, D; Lalloo, D; Khoo, S; Mwapasa, V

Journal article

Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults

Abstract:: There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC0-28 days) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) 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 naïve, (ii) on efavirenz-based ART and (iii) on nevirapine-based ART (n=10-15/group). Ritonavir-boosted lopinavir-based ART group was dropped in step 2 due to 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 compared to ART naïve participants. There were no significant differences in AUC0-28 days between the other ART groups and the ART naïve 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 well tolerated at half and full standard adult treatment courses, efavirenz based antiretroviral regimen was associated with reduced piperaquine exposure which may compromise dihydroartemisinin-piperaquine's effectiveness in programmatic settings.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Banda, C., Dzinjalamala, F., Mukaka, M., Mallewa, J., Maiden, V., Terlouw, D., Lalloo, D., Khoo, S., & Mwapasa, V. (2018). Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults. Antimicrobial Agents and Chemotherapy, 62(8), e00634–18.

MLA Style

Banda, C, et al. “Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Co-Administered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.” Antimicrobial Agents and Chemotherapy, vol. 62, no. 8, 2018, pp. e00634–18.

Chicago Style

Banda, C, F Dzinjalamala, M Mukaka, et al. 2018. “Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Co-Administered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.” Antimicrobial Agents and Chemotherapy 62 (8): e00634–18.
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