Rimawi Bassam H, Johnson Erica, Rajakumar Augustine, Tao Sijia, Jiang Yong, Gillespie Scott, Schinazi Raymond F, Mirochnick Mark, Badell Martina L, Chakraborty Rana
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.
Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.02213-16. Print 2017 Jun.
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 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 ( = 10) and DTG ( = 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.
整合酶抑制剂埃替格韦（EVG）和度鲁特韦（DTG）可迅速降低血浆HIV-1病毒载量，这是预防HIV-1母婴传播的关键因素。尚未有关于这些药物在孕妇脐带血、母体外周血单个核细胞（PBMCs）或胎盘组织中浓度的报道。我们展示了HIV-1感染孕妇母体血、脐带血及胎盘中抗逆转录病毒药物（ARV）的药代动力学数据。母体血和脐带血取自接受埃替格韦、考比司他、富马酸替诺福韦二吡呋酯和恩曲他滨单一固定剂量复方制剂的女性，或取自接受度鲁特韦联合治疗方案的女性。同时获取母体血和脐带血的血浆、PBMCs及绒毛胎盘样本。采用液相色谱-串联质谱法（LC-MS/MS）同时测定药物浓度。利用中位数和范围来解读数据，我们比较了不同基质（母体和脐带血血浆、PBMCs及胎盘）之间的药物浓度比。所有五种药物均通过胎盘从母体转移至胎儿循环。测定了脐带血浆与胎盘、脐带与母体血浆以及脐带PBMCs与母体PBMCs之间埃替格韦、考比司他、替诺福韦及恩曲他滨（ = 10）和度鲁特韦（ = 3）的浓度比。替诺福韦从母体血浆穿过胎盘进入脐带血，然后进入脐带PBMCs，在那里它被磷酸化为其活性形式（二磷酸替诺福韦）。在每个隔室中均检测到这五种抗逆转录病毒药物，突出了这些药物从母体向胎儿循环的转移。
