Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy release_z73mhf5gu5e3tp45mai7q3mxtq

by Bassam H. Rimawi, Erica Johnson, Augustine Rajakumar, Sijia Tao, Yong Jiang, Scott Gillespie, Raymond F. Schinazi, Mark Mirochnick, Martina L. Badell, Rana Chakraborty


<jats:title>ABSTRACT</jats:title> 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 present <jats:italic>in vivo</jats:italic> pharmacokinetic 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 ( <jats:italic>n</jats:italic> = 10) and DTG ( <jats:italic>n</jats:italic> = 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.
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Published in Antimicrobial Agents and Chemotherapy by American Society for Microbiology
ISSN-L 0066-4804
Volume 61
Release Date 2017-03-27
Publisher American Society for Microbiology
Primary Language en (lookup)

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Type  article-journal
Stage   published
Date   2017-03-27
DOI  10.1128/aac.02213-16
PubMed  28348149
PMC  PMC5444129
Wikidata  Q38872808
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ISSN-L:  0066-4804
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