Endotoxin neutralization in human plasma is an excellent indicator of chronic immune activation, which is the most accurate predictor of mortality in HIV. Recently we developed an assay using endotoxin neutralization as an indicator of bacterial translocation. This assay is accurate in discriminating control patients from those with inflammatory bowel disease in addition to indicating disease severity. We propose to adapt our endotoxin neutralization assay for the evaluation of HIV disease severity and progression. In the 6 month Phase I part of the SBIR project, we will (1) collect plasma from 20 19-50 year old HIV-positive males and an equivalent number of demographically similar HIV-negative male subjects and test for viral load and CD4+ T cell count, (2) measure the levels of specific plasma markers indicative of bacterial translocation, immune system activation and/or inflammatory response, and (3) measure immune activation using our endotoxin neutralization biomarker monitor system. Once a neutralization profile of each sample is established, Pearson correlation will be used to determine the relationship between endotoxin neutralization and all factors established in the first two aims. Student's T-test will be used to determine statistical significance between HIV- positive and control groups. The results from Phase I will show whether our endotoxin neutralization system is a convenient, reproducible and inexpensive method to assess the severity of HIV disease. In Phase II of the project, we will use our system to monitor patients over a 1-2 year period to correlate endotoxin neutralization with treatment.
This project addresses the major medical problem of HIV infection which affects 1 million people in the United States at an annual cost of $40 billion. The proposed assay depends on the novel observation that the level of endotoxin neutralization in human plasma correlates with immune system activation due to intestinal permeability, the most significant determinant of mortality in HIV infection. This technology will provide a fast, low-cos biomonitor that could easily be implemented into any clinical setting