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

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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.

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Acknowledgements

This work was supported by NSF grants DMS-1616299 (NKV), DMS-1836647 (NKV), and DEB- 2030479 (NKV) from National Science Foundation, United States, and UGP award (NKV) from San Diego State University. The research of F.-B. Wang was supported in part by the Ministry of Science and Technology, Taiwan, the National Center for Theoretical Sciences, National Taiwan University, and Chang Gung Memorial Hospital (BMRPD18 and NMRPD5M0021). NKV would like to thank National Center for Theoretical Sciences for supporting the NCTS visit, during which some of the work was carried out.

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Authors and Affiliations

  1. Department of Mathematics and Computer Science, Drury University, Missouri, USA

    Colin T. Barker

  2. Department of Natural Science in the Center for General Education, Chang Gung University, Taoyuan 333, Guishan, Taiwan

    Feng-Bin Wang

  3. Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung 204, Keelung Branch, Taiwan

    Feng-Bin Wang

  4. National Center for Theoretical Sciences, National Taiwan University, Taipei 106, Taiwan

    Feng-Bin Wang

  5. Department of Mathematics and Statistics, San Diego State University, California, San Diego, USA

    Naveen K. Vaidya

  6. Computational Science Research Center, San Diego State University, California, San Diego, USA

    Naveen K. Vaidya

  7. Viral Information Institute, San Diego State University, California, San Diego, USA

    Naveen K. Vaidya

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  1. Colin T. Barker
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Correspondence to Naveen K. Vaidya.

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Barker, C.T., Wang, FB. & Vaidya, N.K. Modeling Antiretrovial Treatment to Mitigate HIV in the Brain: Impact of the Blood-Brain Barrier. Bull Math Biol 85, 105 (2023). https://doi.org/10.1007/s11538-023-01204-w

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