Math and Computer Science Honors Theses

Modeling the Limited Immune Reconstitution of HIV-1 Patients on HAART: The Damaged Niche Hypothesis

Date of Creation

2013

Document Type

Departmental Honors Thesis - Restricted Access

Department

Mathematics

First Advisor

David B. Damiano

Abstract

In this project we develop a system of ordinary differential equations (ODE) to model and explore the damaged niche hypothesis for the limited immune reconstitution of HIV patients on highly active antiretroviral therapy (HAART). We have observed limited CD4+ reconstitution in patient data from an ongoing retrospective study at the University of Massachusetts Medical School HIV/AIDS Clinic. The UMass cohort consists of 43 patients who have undergone HAART for at least six years and have maintained undetectable viral loads. Although many patients' peripheral blood T cell counts reconstitute in this time period, for some patients this occurs more slowly or appears to plateau before counts reach normal ranges. The damaged niche hypothesis states that the HIV-induced build-up of collagen in lymph nodes causes irreversible damage to lymph node architecture that disrupts cell signals necessary for naive CD4+ T cell survival. We have created a multi-compartment ODE model with CD4+ T cell subsets, CDS+ T cell subsets. and viral compartments for peripheral blood that is consistent with this hypothesis. We have optimized our healthy and infected model against target values from published results in the literature. Our goal is to elucidate the relative impact of lymph damage. thymic impairment, and CDS+ activation on immune reconstitution.

Comments

Reader: Edward J. Soares

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