Endotoxin Neutralization as a Biomonitor for HIV Disease Progression

ABSTRACTEndotoxin neutralization in human plasma is an excellent indicator of chronic immune activationwhich is an accurate predictor of mortality in HIVinfectionRecently we developed an assay using endotoxin neutralization as an indicator of immune activation due to bacterial translocationThis assay is accurate in discriminating healthy patients from those with inflammatory bowel disease in addition to indicating disease severityPhase I of this project expanded the assay to patients with HIVinfectionThose experiments showed statistically significant differences between healthy controls and HIVinfected patients as well as between anti retroviral therapyARTna ve patients and those actively receiving treatmentAdditionallyendotoxin neutralization correlated as expected with markers of viral loadCDT cell numberinflammatory responsemacrophage activationendotoxin specific immunoglobulin sequestration and endotoxin specific protein productionIn Phase II of this SBIR project we will follow a group of HIVinfectedART na ve patients as they initiate ART and continue treatment over amonth time periodAt specific time points we will collect blood plasma to measure the level of endotoxin neutralizationSpecific Aima panel of traditional biomarkers indicating specific sequelae of the diseaseSpecific Aimand both a quantitative and qualitative analysis of circulatingS rDNASpecific AimWith this datawe will use Pearson correlation and Student s t test to determinedifferences in endotoxin neutralization between HIVinfected patients and a demographically similar healthy control groupthe effect of ART on endotoxin neutralizationthe correlation of endotoxin neutralization with viral loadCDT cell numberintestinal permeabilitybacterial translocationimmune activationinflammatory response and coagulopathyandthe relationship of endotoxin neutralization with the species composition of the microbiomeAdditionallythis project will include experiments to optimize the assay and prepare it for commercializationSpecific Aim