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

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dc.contributor.author Chimbola, Obias Mulenga
dc.contributor.author Lungu, Edward
dc.contributor.author Szomolay, Barbara
dc.date.accessioned 2021-09-28T11:11:51Z
dc.date.available 2021-09-28T11:11:51Z
dc.date.issued 2021-04-12
dc.identifier.citation Chimbola, O. M., Lungu, L. and Szomolay, B. (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), 213-249, https://doi.org/10.1080/17513758.2021.1912420 en_US
dc.identifier.issn 17513766
dc.identifier.uri http://repository.biust.ac.bw/handle/123456789/354
dc.description.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. en_US
dc.description.sponsorship Simons Foundation en_US
dc.language.iso en en_US
dc.publisher Taylor and Francis Ltd en_US
dc.subject HIV-1 en_US
dc.subject HHV-8; en_US
dc.subject Mathematical model en_US
dc.subject Optimal control en_US
dc.title Effect of innate and adaptive immune mechanisms on treatment regimens in an AIDS- related Kaposi's Sarcoma model en_US
dc.description.level phd en_US
dc.description.accessibility unrestricted en_US
dc.description.department mss en_US


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