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01-10-2020 | Human Immunodeficiency Virus

S-EQUOL: a neuroprotective therapeutic for chronic neurocognitive impairments in pediatric HIV

Authors: Kristen A. McLaurin, Hailong Li, Anna K. Cook, Rosemarie M. Booze, Charles F. Mactutus

Published in: Journal of NeuroVirology | Issue 5/2020

Abstract

Chronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.e., resembling a therapeutic for children with PHIV) and across the factor of biological sex. Utilization of a series of signal detection operant tasks revealed prominent, sex-dependent neurocognitive deficits in the HIV-1 Tg rat, characterized by alterations in stimulus-reinforcement learning, the response profile, and temporal processing. Early (i.e., postnatal day 28) initiation of SE treatment precluded the development of chronic neurocognitive impairments in all (i.e., 100%) HIV-1 Tg animals, albeit not for all neurocognitive domains. Most notably, the therapeutic effects of SE are generalized across the factor of biological sex, despite the presence of endogenous hormones. Results support, therefore, the efficacy of SE as a neuroprotective therapeutic for chronic neurocognitive impairments in the post-cART era; an adjunctive therapeutic that demonstrates high efficacy in both males and females. Optimizing treatment conditions by evaluating multiple factors (i.e., age, neurocognitive domains, and biological sex) associated with PHIV and HIV-1 associated neurocognitive disorders (HAND) affords a key opportunity to improve the therapeutic efficacy of SE.

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Title: S-EQUOL: a neuroprotective therapeutic for chronic neurocognitive impairments in pediatric HIV
Authors: Kristen A. McLaurin
Hailong Li
Anna K. Cook
Rosemarie M. Booze
Charles F. Mactutus
Publication date: 01-10-2020
Publisher: Springer International Publishing
Keyword: Human Immunodeficiency Virus
Published in: Journal of NeuroVirology / Issue 5/2020
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-020-00886-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

S-EQUOL: a neuroprotective therapeutic for chronic neurocognitive impairments in pediatric HIV

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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