Pharmacokinetics, Placental and Breastmilk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV.

Hodel, EM ORCID: 0000-0001-5821-1685, Marzolini, C, Waitt, C ORCID: 0000-0003-0134-5855 and Rakhmanina, N
(2019) Pharmacokinetics, Placental and Breastmilk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV. Current pharmaceutical design.

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BACKGROUND:Remarkable progress has been achieved in the identification of HIV infection in pregnant women and prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breastmilk. We also summarized main safety considerations for in utero and breastmilk ARVs exposures in infants. METHODS:We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breastmilk transport of ARVs we selected the studies that provided ratios of maternal to cord (M:C) plasma and breastmilk to maternal plasma (M:P) concentrations, respectively. RESULTS:We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect dosing of several protease inhibitors during pregnancy and limit the use for several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breastmilk and summarized the effect of pregnancy on placental and breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs. CONCLUSIONS:Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal and consequently fetal ARV exposure. Limited available data suggest that expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breastmilk. The drug transporter role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 27 Mar 2019 08:11
Last Modified: 20 Mar 2020 02:30
DOI: 10.2174/1381612825666190320162507

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