title: Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy.
abstract: The integrase inhibitors elvitegravir (EVG) and dolutegravir (DTG) rapidly decrease the plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentrations of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMCs), or placental tissue in pregnant women. We presentin vivopharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood and within placentae from HIV-1-infected pregnant women. Maternal blood and cord blood were obtained from women receiving EVG, cobicistat, tenofovir disoproxil fumarate, and emtricitabine as a single fixed-dose combination formulation or DTG as part of a combination regimen. Plasma and PBMCs from maternal and cord blood were obtained along with villous placental samples. Drug concentrations were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Utilizing medians and ranges to interpret our data, we compared the drug concentration ratios between different matrices (maternal and cord blood plasma, PBMCs, and placenta). All five agents transferred from maternal into fetal circulation via the placenta. Concentration ratios for EVG, cobicistat, tenofovir, and emtricitabine (n= 10) and DTG (n= 3) were determined between cord plasma and placenta, cord and maternal plasma, and cord PBMCs and maternal PBMCs. TFV moves from maternal plasma through the placenta to the cord blood and then into cord PBMCs, where it is phosphorylated into its active forms (TFV diphosphate). These five ARVs were detected in each of the compartments, highlighting transfer of these agents from the maternal into the fetal circulation.
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA bassamrimawi@yahoo.com.|Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Bassam H
authors.identifier: 0000-0002-8178-9212
authors.initials: BH
authors.lastname: Rimawi
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Division of Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Johnson
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Center for AIDS Research, Laboratory of Biochemical Pharmacology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Sijia
authors.initials: S
authors.lastname: Tao
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Center for AIDS Research, Laboratory of Biochemical Pharmacology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Division of Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Gillespie
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Center for AIDS Research, Laboratory of Biochemical Pharmacology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.affiliation: Department of Pediatrics, Division of Neonatology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Gynecology and Obstetrics, Division of Maternal Fetal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Martina L
authors.initials: ML
authors.lastname: Badell
authors.affiliation: Emory University, School of Medicine, Atlanta, Georgia, USA.|Department of Pediatrics, Division of Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Chakraborty
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006575:Heterocyclic Compounds, 3-Ring / Q000493:pharmacokinetics*; D006801:Humans; D010078:Oxazines; D010879:Piperazines; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011728:Pyridones; D015363:Quinolones / Q000493:pharmacokinetics*; D055815:Young Adult; D000099226:Dolutegravir
chemical_list: D044966:Anti-Retroviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones; D000099226:Dolutegravir; C509700:elvitegravir
keywords: HIV-1; dolutegravir; elvitegravir; integrase inhibitors; pharmacokinetics; placental transfer; pregnancy