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Clin Pharmacol Ther. 2017 Sep;102(3):520-528. doi: 10.1002/cpt.664. Epub 2017 May 30.

Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention.

Author information

1
Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
2
Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda.
3
Department of Clinical Pharmacy, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
4
Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
5
Department of Pediatrics, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.

Abstract

Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed the 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 nonpregnant 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 nonpregnant 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.

PMID:
28187497
PMCID:
PMC5546920
DOI:
10.1002/cpt.664
[Indexed for MEDLINE]
Free PMC Article

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