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Dynamics of Naive and Memory CD4 T-cells in Chronically Infected HIV Patients Post-Injection of Down-Modulated CCR5 Memory CD4-Cells

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dc.contributor.advisorHeffernan, Jane M.
dc.creatorRaad, Angie
dc.date.accessioned2016-11-25T14:16:09Z
dc.date.available2016-11-25T14:16:09Z
dc.date.copyright2016-08-16
dc.date.issued2016-11-25
dc.date.updated2016-11-25T14:16:08Z
dc.degree.disciplineApplied and Industrial Mathematics
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractHIV/AIDS, a sexually transmitted diseases continues to affect the lives of millions of individuals worldwide. This retrovirus targets CD4 T-cell populations, the main driver of the immune system by using the chemokine co-receptor 5 (CCR5). Despite the success of the highly active antiretroviral therapy in reconstituting the immune system, HIV infected individuals still suffer from low CD4 T-cell counts. Recently, researchers were able to highlight the success of immunotherapy in restoring the CD4 T-cell count. To further, investigate such importance, our collaborators at case Western University injected CCR5-down-modulated memory CD4 T-cells into 9 chronically infected HIV patients. Using a linear transitions from the naive to the effector memory state, a non linear ordinary differential equation model was used to model the experiment. Various data fitting techniques in Matlab Stan and Monolix software were used to estimate the model parameters (proliferation, death, transition and birth rates) before and after the initiation of the treatment to study the change of the cell dynamics. Our fittings have indicated an increase in the memory stem and na\"{\i}ve cell lifespan post-clinical trial. Using sensitivity analysis, we showed that the na\"{\i}ve cell birth rate from the thymus lambda, the memory stem cell proliferation rate p_ST and the central memory cell death rate d_C played an important role in restoring the CD4 T-cell count. A stochastic model for the CD4 T-cells population was developed to examine if fluctuations from the stochastic simulation were able to capture the experimental data measurements. The findings of this study indicates the importance of looking further into how modified CD4 T-cells are able to restore the T-cell counts which thereby decrease the HIV virus pool and help HIV patients to maintain a low level of the virus and most importantly a high level of T-cell count.
dc.identifier.urihttp://hdl.handle.net/10315/32769
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectStatistics
dc.subject.keywordsHIV
dc.subject.keywordsDisease modelling
dc.subject.keywordsData fitting
dc.subject.keywordsLHS
dc.subject.keywordsMemory CD4 T-cells
dc.subject.keywordsStochastic
dc.titleDynamics of Naive and Memory CD4 T-cells in Chronically Infected HIV Patients Post-Injection of Down-Modulated CCR5 Memory CD4-Cells
dc.typeElectronic Thesis or Dissertation

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