This proposal addresses the need for a simple, low-cost diagnostic to monitor T cell function in HIV-infected patients. Experience with HIV patients undergoing highly active anti-retroviral therapy (HAART) has shown that total T cell count is a useful but insufficient measure of the functional status of the immune system. A more pertinent indicator would be the quantity and quality of HIV-specific memory T cells, and it is believed this subpopulation can be determined by measuring the expression profile of genes linked to memory T cell function. The proposed diagnostic is based on a novel optical chip that is ideally suited for routine, low-density array testing. There is no need for the complex processing steps or expensive analytical instruments associated with conventional high-density array gene chips, and it is expected that the disposable optical chips can be mass-produced for <$5. The Phase I program will use an existing LCMV mouse model to establish feasibility. A prototype optical chip for quantifying the expression profile of several genes linked to CD8 memory T-cell function will be developed and assessed. If successful, a follow-on Phase II program will focus directly on monitoring memory T cell function in HIV-infected humans.
A practical, low-cost diagnostic for monitoring HIV-specific T cell function would be a valuable adjunct to T cell counts and viral loads in regulating patients undergoing HAART and other treatment regimens. In addition, the basic test format could easily be applied to other immune-related disorders, pharmacogenomics and clinical trials.
