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Exploiting immune response dynamics in HIV therapy

Posted on:2005-09-07Degree:Ph.DType:Dissertation
University:University of California, Santa BarbaraCandidate:Zurakowski, Ryan MarkFull Text:PDF
GTID:1454390008490771Subject:Engineering
Abstract/Summary:PDF Full Text Request
The Human Immunodeficiency Virus (HIV) infects cells involved in the regulation of the adaptive immune response. Untreated infection usually leads to severe immunodeficiency and death from opportunistic infections. However, recent experimental work has shown that the natural immune response to HIV can be enhanced through the use of schedules of interrupted therapy. In some cases, this enhancement is sufficient to induce a persistent, drug free state in which the virus is controlled to low levels and the patient exhibits no progressive deterioration of the immune system.; Clinical trials attempting to use interrupted treatment schedules to exploit this phenomenon have had mixed results. Recent modeling work that explains the behavior shows that the immune response to HIV is governed by nonlinear dynamics that are sensitive to small parameter variations. It is unlikely, therefore, that a single schedule of interrupted treatment would yield consistent results across a number of patients.; In order to successfully induce immune-mediated control of HIV infection with a greater degree of success, it will likely be necessary to use a method of calculating interruption schedules that will accommodate variations unique to the patient based on measurements made during treatment. We introduce a framework based on nonlinear Model Predictive Control to determine appropriate interruption schedules for exploiting the natural immune response to HIV. This framework incorporates models of the immune response, and uses feedback measurements to provide robustness to the modeling and measurement errors inherent in the application. The method is designed to be implementable in a clinical setting.
Keywords/Search Tags:Immune response, HIV
PDF Full Text Request
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