title: Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention.
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 AUC0-21dwas 40% lower in pregnant women compared to nonpregnant women. DHA AUC0-8hrand piperaquine AUC0-21dwere 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.
authors.affiliation: Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.|Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: R
authors.initials: R
authors.lastname: Kajubi
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: P
authors.initials: P
authors.lastname: Jagannathan
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: N
authors.initials: N
authors.lastname: Chamankhah
authors.affiliation: Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: M
authors.initials: M
authors.lastname: Were
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ruel
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Koss
authors.affiliation: Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: A
authors.initials: A
authors.lastname: Kakuru
authors.affiliation: Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.|Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: N
authors.initials: N
authors.lastname: Mwebaza
authors.affiliation: Infectious Disease Research Collaboration, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: M
authors.initials: M
authors.lastname: Kamya
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Havlir
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Rosenthal
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco General Hospital, San Francisco, California, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Aweeka
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008288:Malaria / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D014454:Uganda; D055815:Young Adult; D010879:Piperazines
chemical_list: D000480:Alkynes; D000962:Antimalarials; D037621:Artemisinins; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors; C039060:artenimol; C034759:piperaquine; D010879:Piperazines; C098320:efavirenz