Research Project
9255232
ABSTRACT Endotoxin neutralization in human plasma is an excellent indicator of chronic immune activation, which is an accurate predictor of mortality in HIV-1 infection. Recently we developed an assay using endotoxin neutralization as an indicator of immune activation due to bacterial translocation. This assay is accurate in discriminating healthy patients from those with inflammatory bowel disease in addition to indicating disease severity. Phase I of this project expanded the assay to patients with HIV-1 infection. Those experiments showed statistically significant differences between healthy controls and HIV-1-infected patients as well as between anti-retroviral therapy (ART)-naïve patients and those actively receiving treatment. Additionally, endotoxin neutralization correlated as expected with markers of viral load, CD4+ T cell number, inflammatory response, macrophage activation, endotoxin-specific immunoglobulin sequestration and endotoxin-specific protein production. In Phase II of this SBIR project we will follow a group of HIV-1-infected, ART-naïve patients as they initiate ART and continue treatment over a 6 month time period. At specific time points we will collect blood plasma to measure the level of endotoxin neutralization (Specific Aim #2), a panel of traditional biomarkers indicating specific sequelae of the disease (Specific Aim #3) and both a quantitative and qualitative analysis of circulating 16S rDNA (Specific Aim #3). With this data, we will use Pearson correlation and Student?s t-test to determine (1) differences in endotoxin neutralization between HIV-1-infected patients and a demographically similar healthy control group, (2) the effect of ART on endotoxin neutralization, (3) the correlation of endotoxin neutralization with viral load, CD4+ T cell number, intestinal permeability, bacterial translocation, immune activation, inflammatory response and coagulopathy, and (4) the relationship of endotoxin neutralization with the species composition of the microbiome. Additionally, this project will include experiments to optimize the assay and prepare it for commercialization (Specific Aim #1).
