Maternal-Fetal Transfer and Amniotic Fluid Accumulation of Nucleoside Analogue Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus-Infected Pregnant Women

Abstract

ABSTRACT This study was performed to investigate placental transfer of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A total of 100 HIV type 1-infected mothers receiving antiretroviral therapy, including one or more NRTIs, for clinical indications at the time of delivery were enrolled. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean section, and paired cord blood samples were obtained by venipuncture immediately after delivery. Drug concentrations were measured by using high-performance liquid chromatography. A significant relationship between concentrations in maternal and cord plasma samples was found for zidovudine, lamivudine, stavudine, and didanosine. The ratio between the concentrations in cord and maternal plasma samples ( R ) was high for zidovudine ( R = 1.22), its glucuronide metabolite (3′-azido-3′-deoxythymidine-β- d -glucuronide) ( R = 1.01), stavudine ( R = 1.32), lamivudine ( R = 0.93), and abacavir ( R = 1.03) and was low for didanosine ( R = 0.38). The ratio between the concentrations in amniotic fluid and cord plasma samples was high for zidovudine ( R = 2.24), its glucuronide metabolite ( R = 2.83), stavudine ( R = 4.87), and lamivudine ( R = 3.99) and was lower for didanosine ( R = 1.14). These findings indicate that most NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic fluid, probably through fetal urinary excretion. The efficacy or toxicity of NRTIs may vary according to placental transfer.