Evaluating Neurodevelopmental Consequences of Perinatal Exposure to Antiretroviral Drugs: Current Challenges and New Approaches release_limdejs5ljbv5asfsvgmt7pzsu

by Jordan G. Schnoll, Brian Temsamrit, Daniel Zhang, Hongjun Song, Guo-li Ming, Kimberly M. Christian

Abstract

As antiretroviral therapy (ART) becomes increasingly affordable and accessible to women of childbearing age across the globe, the number of children who are exposed to Human Immunodeficiency Viruses (HIV) but remain uninfected is on the rise, almost all of whom were also exposed to ART perinatally. Although ART has successfully aided in the decline of mother-to-child-transmission of HIV, the long-term effects of in utero exposure to ART on fetal and postnatal neurodevelopment remain unclear. Evaluating the safety and efficacy of therapeutic drugs for pregnant women is a challenge due to the historic limitations on their inclusion in clinical trials and the dynamic physiological states during pregnancy that can alter the pharmacokinetics of drug metabolism and fetal drug exposure. Thus, much of our data on the potential consequences of ART drugs on the developing nervous system comes from preclinical animal models and clinical observational studies. In this review, we will discuss the current state of knowledge and existing approaches to investigate whether ART affects fetal brain development, and describe novel human stem cell-based strategies that may provide additional information to better predict the impact of specific drugs on the human central nervous system. Graphical Abstract Approaches to evaluate the impact of drugs on the developing brain. Dysregulation of the developing nervous system can lead to long-lasting changes. Integration of data from animal models, clinical observations, and cell culture studies is needed to predict the safety of therapeutic antiretroviral drugs during pregnancy. New approaches include human induced pluripotent stem cell (iPSC)-based 2D and 3D models of neuronal networks and brain regions, as well as single cell profiling in response to drug exposure.
In text/plain format

Published in Journal of Neuroimmune Pharmacology by Springer Science and Business Media LLC
ISSN-L 1557-1890
Release Date 2019-09-11
Container Type journal
Publisher Springer Science and Business Media LLC
Primary Language en (lookup)

Known Files and URLs

There are no accessible files associated with this release. You could check other releases for this work for an accessible version.

No Full Text Available "Save Paper Now"
Know of a fulltext copy of on the public web? Submit a URL and we will archive it
Type  article-journal
Stage   published
Date   2019-09-11
Container Metadata
Unknown OA Status
Not in DOAJ
Not in ISSN ROAD
ISSN-L:  1557-1890
Fatcat Entry
Work Entity
grouping other versions (eg, pre-print) and variants of this release
Cite This Release
Fatcat Bits

State is "active". Revision:
730aa34f-877c-45a5-8c3b-c68619b174c5
As JSON object via API