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Effect of innate and adaptive immune mechanisms on treatment regimens in an AIDS-related Kaposi's Sarcoma model

Chimbola, Obias Mulenga, Lungu, Edward M. and Szomolay, Barbara 2021. Effect of innate and adaptive immune mechanisms on treatment regimens in an AIDS-related Kaposi's Sarcoma model. Journal of Biological Dynamics 15 (1) , pp. 213-249. 10.1080/17513758.2021.1912420

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Abstract

Kaposi Sarcoma (KS) is the most common AIDS-defining cancer, even as HIV-positive people live longer. Like other herpesviruses, human herpesvirus-8 (HHV-8) establishes a lifelong infection of the host that in association with HIV infection may develop at any time during the illness. With the increasing global incidence of KS, there is an urgent need of designing optimal therapeutic strategies for HHV-8-related infections. Here we formulate two models with innate and adaptive immune mechanisms, relevant for non-AIDS KS (NAKS) and AIDS-KS, where the initial condition of the second model is given by the equilibrium state of the first one. For the model with innate mechanism (MIM), we define an infectivity resistance threshold that will determine whether the primary HHV-8 infection of B-cells will progress to secondary infection of progenitor cells, a concept relevant for viral carriers in the asymptomatic phase. The optimal control strategy has been employed to obtain treatment efficacy in case of a combined antiretroviral therapy (cART). For the MIM we have shown that KS therapy alone is capable of reducing the HHV-8 load. In the model with adaptive mechanism (MAM), we show that if cART is administered at optimal levels, that is, 0.48 for protease inhibitors, 0.79 for reverse transcriptase inhibitors and 0.25 for KS therapy, both HIV-1 and HHV-8 can be reduced. The predictions of these mathematical models have the potential to offer more effective therapeutic interventions in the treatment of NAKS and AIDS-KS.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Taylor & Francis
ISSN: 1751-3758
Date of First Compliant Deposit: 28 April 2021
Date of Acceptance: 16 March 2021
Last Modified: 28 Apr 2021 09:15
URI: https://orca.cardiff.ac.uk/id/eprint/140798

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