Modeling Antiretrovial Treatment to Mitigate HIV in the Brain: Impact of the Blood-Brain Barrier

Abstract Current research in Human Immunodeficiency Virus (HIV) focuses on eradicating virus reservoirs that prevent or dampen the effectiveness of antiretroviral treatment (ART). One such reservoir, the brain, reduces treatment efficacy via the blood-brain barrier (BBB), causing an obstacle to drug penetration into the brain. In this study, we develop a mathematical model to examine the impact of the BBB on ART effectiveness for mitigating brain HIV. A thorough analysis of the model allowed us to fully characterize the global threshold dynamics with the viral clearance and persistence in the brain for the basic reproduction number less than unity and greater than unity, respectively. Our model showed that the BBB has a significant role in inhibiting the effect of ART within the brain despite the effective viral load suppression in the plasma. The level of impact, however, depends on factors such as the CNS Penetration Effectiveness (CPE) score, the slope of the drug dose-response curves, the ART initiation timing, and the number of drugs in the ART protocol. These results suggest that reducing the plasma viral load to undetectable levels due to some drug regimen may not necessarily indicate undetectable levels of HIV in the brain. Thus, the effect of the BBB on viral suppression in the brain must be considered for developing proper treatment protocols against HIV infection..

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:85

Enthalten in:

Bulletin of mathematical biology - 85(2023), 11 vom: 21. Sept.

Sprache:

Englisch

Beteiligte Personen:

Barker, Colin T. [VerfasserIn]
Wang, Feng-Bin [VerfasserIn]
Vaidya, Naveen K. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

42.11$jBiomathematik$jBiokybernetik

44.00$jMedizin: Allgemeines

Themen:

Antiretroviral therapy
HIV in the brain

RVK:

RVK Klassifikation

Anmerkungen:

© The Author(s), under exclusive licence to Society for Mathematical Biology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s11538-023-01204-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2145651497

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