Human Immunodeficiency Virus -1 infects CD4+ cells, and the subsequent loss of these cells cause Acquired Immune Deficiency Syndrome. Highly active antiretroviral therapy (HAART) is crucial to control viremia in the clinical management of AIDS/HIV infection; however, drug regimens are complex, expensive, and require life-long intervention with potential side effects. Current conventional anti-HIV drugs target different phases of the HIV life cycle and can be categorized as nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, entry inhibitors (co-receptor antagonists and fusion inhibitors), and integrase inhibitors(II). Enfuvirtide (Fuzeon, or T-20) is the first fusion inhibitor approved by the FDA and has substantial side effects and drug delivery issues with most patients developing some local injection site reaction. The subcutaneous application of enfuvirtide and its short half-life, which requires twice daily administration, has disadvantages in patients who are already burdened by complex oral therapy. To overcome these drug issues, we propose an alternative method to administer the HIV-1 peptide fusion inhibitor C46. Stem cells can be a vehicle for delivering genes to specific tissues in the body and their therapeutic delivery systems are extensively used in cancer research. For many years, restoration of blood and immune system function has been used as a component in the care of cancer patients who have been treated with chemotherapeutic agents. Mesenchymal Stem Cells (MSCs) have been demonstrated as a delivery vehicle for gene therapy applications based on their ability to engraft and home to inflamed tissues. MSCs are multi-potent and have immunological function in several human diseases. To investigate MSCs immune suppressive ability in HIV infection system, we will evaluate the crosstalk between MSCs and HIV infection immune-modulatory network. / acase@tulane.edu

Current research on HIV therapy is diverse and multi-disciplinary. Engineers however, were late in joining the research movement and as such, engineering literature related to HIV chemotherapy is limited. Control engineers in particular, should have risen to the challenge, as it is apparent that HIV chemotherapy and control engineering have a lot in common. From a control theoretic point of view, HIV chemotherapy is control of a time varying nonlinear dynamical system with constrained controls. Once a suitable model has been developed or identified, control system theoretical concepts and design principles can be applied. The adopted control approach or strategy depends primarily on the control objectives, performance specifications and the control constraints. In principle, the designed control system can then be validated with clinical data. Obtaining measurements of the controlled variables however, has the potential to hinder effective control. The first part of this research focused on the application of control system analytical tools to HIV/AIDS models. The intention was to gain some insights into the HIV infection dynamics from a control theoretic perspective. The issues that needed to be addressed are: Persistent virus replication under potent HAART, variability in response to therapy between individuals on the same regimen, transient rebounds of plasma viremia after periods of suppression, the attainment, or lack thereof, of maximal and durable suppression of the viral load. The questions to answer were: When are the above mentioned observed responses to therapy most likely to occur as the HIV infection progresses, and does attaining one necessarily imply the other? Furthermore, the prognostic markers of virologic success, the possibility of individualizing therapy and timing the initiation of antiretroviral therapy such that the benefits of therapy are maximized, are matters that were also investigated. The primary objective of this thesis was to analyze models for the eventual control of the HIV infection. HIV therapy has multiple and often conflicting objectives, and these objectives had to be prioritized. The intention of the proposed control strategy was to produce practical solutions to the current antiretroviral problems. To this end, the second part of the research focused on addressing the HIV/AIDS control issues of sampling for effective control given the invasive nature of drawing blood from a patient and the derivation of drug dosage sequences to strike a balance between maximal suppression and toxicity reduction, when multiple drugs are concomitantly used to treat the infection. / Thesis (PhD)--University of Pretoria, 2006. / Electrical, Electronic and Computer Engineering / Unrestricted