Serum-derived bovine immunoglobulin increases peripheral and mucosal CD4 T cell count (MUC8P.736)

Abstract

Abstract A multi-center trial in HIV-enteropathy was conducted to evaluate the impact of serum-derived bovine immunoglobulin (SBI) on markers of peripheral and mucosal immunity as previously reported. Participants (pts) with HIV enteropathy were randomized to SBI 2.5 vs 5.0 g BID or placebo (PBO) during a 4-wk lead-in phase followed by SBI 2.5 vs 5.0 g BID for 20 wks. 103 pts were enrolled with a mean duration of HIV, ART, and enteropathy over 15, 5 and 5 years, respectively. While there was no evidence for a median change in peripheral CD4 counts in all pts from baseline to wk 24 (681 to 661 cells/mL), significant increases were observed among pts in the lowest quartile (n=24)(311 to 366 cells/mL, p=0.002). In this subgroup the SBI pts had increased CD4 counts at wk 4 vs PBO pts (median +42 vs ‑16 cells/mL, p=0.02) which was maintained through wk 24. The mean plasma zonulin levels increased from 358(±317) to 812(±423) ng/mL (p<0.001) for pts receiving SBI through 24 weeks. Duodenal CD4 densities increased from 217 to 329 cells/mm2 (median increase of 145 cells/mm2 [p=0.02]) in biopsies obtained from 8 pts, confirming earlier findings. Duodenal crypt cells expressing Ki67 decreased in 6/7 pts from 41% to 24% (p=0.08) which correlated with the decreased number of Paneth cells per crypt (p=0.048). SBI may be a novel therapy to restore mucosal immunity and impact systemic immune reconstitution among pts who have not achieved normal CD4 counts despite prolonged suppressive ART.