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

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

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Antimalarials / administration & dosage*
  • Antimalarials / pharmacokinetics
  • Area Under Curve
  • Artemisinins / administration & dosage*
  • Artemisinins / pharmacokinetics
  • Benzoxazines / administration & dosage*
  • Chemoprevention / methods
  • Cyclopropanes
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy
  • Humans
  • Malaria / prevention & control*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Parasitic / prevention & control
  • Quinolines / administration & dosage*
  • Quinolines / pharmacokinetics
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Uganda
  • Young Adult

Substances

  • Alkynes
  • Antimalarials
  • Artemisinins
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Quinolines
  • Reverse Transcriptase Inhibitors
  • dihydroartemisinin
  • piperaquine
  • efavirenz