Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART

Abstract

Background: Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.Methods: In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.Results: One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/mL, P = 0.002) and zonulin (-4.90 ng/mL, P = 0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/mL, P = 0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/mL), CD4+ T-cell counts increased significantly (26 cells/mL; P = 0.002).Conclusions: Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART.Keywords: HIV infection; CD4 T cell; Serum bovine immunoglobulin protein; Interleukin; Inflammation; Intestine; I-FABP