1. Antiretroviral Therapy With Efavirenz Accentuates Pregnancy‐Associated Reduction of Dihydroartemisinin‐Piperaquine Exposure During Malaria Chemoprevention
- Author
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Kajubi, R, Huang, L, Jagannathan, P, Chamankhah, N, Were, M, Ruel, T, Koss, CA, Kakuru, A, Mwebaza, N, Kamya, M, Havlir, D, Dorsey, G, Rosenthal, PJ, and Aweeka, FT
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Infectious Diseases ,Women's Health ,Sexually Transmitted Infections ,Clinical Research ,Malaria ,HIV/AIDS ,Vector-Borne Diseases ,Pregnancy ,Rare Diseases ,3.3 Nutrition and chemoprevention ,Prevention of disease and conditions ,and promotion of well-being ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Adolescent ,Adult ,Alkynes ,Antimalarials ,Area Under Curve ,Artemisinins ,Benzoxazines ,Chemoprevention ,Cyclopropanes ,Dose-Response Relationship ,Drug ,Drug Combinations ,Drug Interactions ,Female ,HIV Infections ,Humans ,Pregnancy Complications ,Infectious ,Pregnancy Complications ,Parasitic ,Quinolines ,Reverse Transcriptase Inhibitors ,Uganda ,Young Adult ,Pharmacology and Pharmaceutical Sciences ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences - 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.
- Published
- 2017