Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

Objectives:To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design:Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5g twice daily with a 4-week washout period and an optional 9-month extension study. Methods:HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. Results:All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P=0.008) and improvements in stool consistency (P=0.008). Gut permeability was normal before and after the intervention, but d-xylose absorption increased in seven of eight participants. Mucosal CD4(+) lymphocyte densities increased by a median of 139.5cells/mm(2) from 213 to 322cells/mm(2) (P=0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P=0.039), and then fell below baseline in four of five who continued receiving SBI (P=0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4(+) lymphocyte densities (r=-0.74, P=0.046). Conclusion:SBI significantly increases intestinal mucosal CD4(+) lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.