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Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention. Clinical pharmacology & therapeutics Kajubi, R., Huang, L., Jagannathan, P., Chamankhah, N., WERE, M., Ruel, T., Koss, C. A., Kakuru, A., Mwebaza, N., Kamya, M., Havlir, D., Dorsey, G., Rosenthal, P. J., Aweeka, F. T. 2017

Abstract

Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected non-pregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to non-pregnant women. DHA AUC0-8hr and piperaquine AUC0-21d were 27% and 38% lower, respectively in pregnant women receiving efavirenz compared to HIV-uninfected pregnant women. Exposure to DHA and piperaquine were lower among pregnant women and particularly in women on efavirenz, suggesting a need for dose modifications. The study of modified dosing strategies for these populations is urgently needed. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/cpt.664

View details for PubMedID 28187497