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  XIX International AIDS Conference
July 22-27, 2012
Washington, DC
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SBI for HIV Diarrhea
  from Jules: 8 HIV+ individuals with "HIV enteropathy, diarrhea, were given SBI (Serum-derived bovine immunoglobulin) for 8 weeks in this small preliminary study. SBI is a protein isolate derived from bovine plasma in the process of manufacturing purified BSA. The product contains >50% total immunoglobulins consisting of mainly IgG (>45%) and IgM (>5%). Markers of inflammation & activation were unchanged after 8 weeks of SBI, but patients reported improvements in diarrhea. A larger randomized study appears to be planned.
Oral serum-derived bovine immunoglobulin (SBI) administration leads to duodenal gastrointestinal-associated lymphoid tissue (GALT) CD4+ T-lymphocyte increases and improved small intestinal absorption function in an 8-week pilot study in patient
Reported by Jules Levin
IAC 2012 Wash DC
July 22-27
Presented by David Michael Asmuth (United States).
HIV Enteropathy:
Definition: A syndrome characterized by chronic, well-established DIARRHEA (greater than one month in duration) without an identified infectious cause after thorough evaluation, in an HIV-positive individual. It is thought to be due to direct or indirect effects of HIV on the enteric mucosa. HIV enteropathy is a diagnosis of exclusion and can be made only after other forms of diarrheal illness have been ruled out. (Harrison's Principles of Internal Medicine, 13th ed, pp1607-8; Haubrich et al., Bockus Gastroenterology, 5th ed, p1155)
"- Bowel movements/day decreased from 5.7 (5, 8.4) to 2 (2, 3.8)(p=0.013)
- stool consistency [1-formed to 6-watery] decreased from 5.3 (5, 6) to 3 (2.2, 3.8)(p=0.013).
- The GI questionnaire [assesses cramping, urgency, incontinence, and nocturnal diarrhea (possible score from 0 to 24 with normal < 2)] decreased from 6 (5, 11) to 0.5 (0, 5.5) (p=0.013)."


Program Abstract
Background: HIV-infection leads to GALT CD4+ T-cell depletion that persists despite prolonged antiretroviral therapy (ART). SBI is a medical food that neutralizes bacterial antigens and reduces gut inflammation in animal models.
Methods: Subjects on ART with diarrhea and a thorough negative GI-workup received SBI (EnteraHealth, Ankeny,IA,USA) 2.5 grams BID for 8 weeks. 4-hour urine disaccharide gut permeability and absorption test and duodenal biopsies were obtained before and at 8-weeks. Immunohistochemistry for CD3/CD4 was performed on biopsies and flow cytometry was performed on duodenal single-cell suspensions and PBMCs for lymphocyte subsets. Markers of bacterial translocation and cytokine levels were measured in plasma. Stool was collected for 16S rDNA quantification and sequencing. Median values (interquartile ranges) and nonparametric analysis are reported.
Results: All 8 subjects experienced resolution of GI-related symptoms. D-xylose absorption increased in 7/8 subjects and in those with improvement, the absorption levels increased from 31.4 mgs (28.5, 38.8) to 41.5 mgs (33.7, 45.2)(p=0.016). Gut permeability was normal before [0.024% (0.0, 0.048)] and after [0.032% (0.0, 0.047)] intervention (normal< 0.050%). Median duodenal tissue CD4+ T-cell% was unchanged at 16%. Lipopolysaccharide, sCD14, IFN-γ, IL-10, IL-12p70, IL-8, IL-6, and TNF-α were in the normal range before and unchanged after 8-weeks. Absolute lamina propria CD3/CD4 T-cell density increased from 199 cells/mm2 (129, 253) to 274 (216, 370)(p=0.062) after 8-weeks of SBI [normal values 836 cells/mm2 (474, 1050)]. Previous studies show increases of less than 50 cells/mm2 after 9 months of ART. Log10 absolute 16S rDNA stool quantification was unchanged between baseline and week-8 [7.125 cp/gm (6.34, 7.5) to 7.415 (6.4, 7.56)].
Conclusions: SBI improved GI absorption and increased GALT CD4+ T-lymphocyte density. Further research is needed to demonstrate whether alterations in gut microbiota or inflammatory milieu impact mucosal immunology. Longer studies are needed to examine the mechanisms of SBI in GALT immune reconstitution and improvement in HIV enteropathy.