(261e) HIV Infection Dynamics & Treatment Using a Compartmentalized Model of the Lymphatic & Blood Systems

Authors: 
Khalili, S. - Presenter, The Pennsylvania State University
Arazawa, A. - Presenter, The Pennsylvania State University
Armaou, A. - Presenter, Pennsylvania State University


Human immunodeficiency virus (HIV) infection has received a lot of attention because of its global presence, various forms of contraction, and long-term fatal effects. In the pursuit of a cure for the disease, mathematical models have become a useful tool to help understand the dynamics of the HIV virus in vivo. Numerous mathematical models have been proposed in open literature to describe the behavior of the disease. Each of these models captures different aspects of disease progression and removal. These models have several useful applications such as developing optimal treatment schedules later in the infection, when the viral load has reached high concentration and the body immune system has weakened. Additionally, these models have shown that if medication starts immediately after infection, when the viral load is low, there is a chance to cure an otherwise fatal disease [1].

However, most models neglect one important factor of the disease, namely the viral reservoirs that are created after the infection has been established. For this reason, even though antiretroviral treatment has shown the capability to reduce viral concentration to a level below detection in the blood, the infection still persists [2]. In order for mathematical models to accurately describe such a phenomenon, in addition to the blood system, we need to account for reservoirs of virus particles that exist throughout the body, with the prominent one being the lymphatic system.

Follicular dendritic cells (FDCs) play an important role in the immune response. They assist in B cell maturation by the presentation of intact antigen to the B cells, which induces class switching and proliferation. FDCs trap large pools of virus particles on their surfaces in the germinal centers of the lymph nodes. This occurs throughout the entire course of the infection, with an infection pool on the order of 1010 virus particles [3]. The reservoirs on the surface of FDCs are protected from antiretroviral treatments, meaning virus particles may remain viable for years following the initiation of treatment. Because of these FDCs and other differences, the dynamics of the infection differ significantly between the lymphatic and blood systems.

The purpose of this work is to predict the progression of the infection and design a treatment regime based on a compartmentalized mathematical model of the HIV infection. The model includes two interconnected compartments to represent the blood and lymphatic systems. By predicting the viral populations in both compartments, we are able to more accurately identify the efficiency of different treatment regimes and perform a sensitivity analysis. Ultimately, a more holistic understanding of the HIV infection is gained by observing how the interplay of two compartments allows the infection to persist under current treatments.

[1] S. Khalili, A. Armaou, (2008). ?An extracellular stochastic model of early HIV infection and the formulation of optimal treatment policy,? Chemical Engineering Science, 63, pp 4361-4372

[2] S. J. Snedecor, (2006). ?Feasibility of Weekly HIV Drug Delivery to Enhance Drug Localization in Lymphoid Tissues Based on Pharmacokinetic Models of Lipid-Associated Indinavir,? Pharmaceutical Research,? Pharmaceutical Research, 23, pp 1750

[3] A. T. Haase, (1999). ?POPULATION BIOLOGY OF HIV-1 INFECTION: Viral and CD4+ T Cell Demographics and Dynamics in Lymphatic Tissues,? Annu. Rev. Immnol., 17, pp 625-656.