Increased small intestinal and colonic permeability, and loss of villus tip surface area, correlates with microbial translocation and immune activation in HIV (71.5)

Abstract

Abstract As early diagnosis and viremic control of HIV becomes more prevalent, the clinical focus has turned to preventing co-morbidities that include cardiovascular, hepatic, neurological, and metabolic abnormalities and immune exhaustion. Immune activation, as measured by leukocyte activation and soluble inflammatory mediators in circulation, is increased in HIV patients, even those on effective HAART therapy, and is a better predictor of disease progression and of all-cause mortality than viral load. Intestinal permeability, which often leads to microbial products in the bloodstream, may provide a cause for chronic inflammation in HIV patients. Here, we provide corroborating evidence of small intestinal and colonic permeability in a cohort of HIV patients with increased LPS, determined by measuring the excretion of various saccharides. Levels of lactulose and mannitol (small intestinal permeability) and sucralose (colonic permeability) were elevated (p=0.0014 and p<0.001, respectively) in the urine of HIV patients, independent of HAART status. Further analysis of the saccharide excretion profile revealed that HIV patients have a loss of villus tip surface area in the small intestine as compared to controls (p<0.001). These results were correlated to markers of bowel damage and microbial translocation (LPS Binding Protein, EndoCAb, sCD14, I-FABP) and immune activation (CRP, IL-6, IFN-α) and to clinical parameters in hopes of identifying key risk factors for disease progression.