Pilot Study of Oral Probiotic Bacteria Supplementation to Reduce Chronic Immune Activation in HIV-infected Malian Women

Summary

The composition of the intestinal bacterial flora effects gut immunologic function and intestinal barrier integrity. HIV infection impairs gut immune and epithelial function resulting in an altered gut bacterial flora and "leakage" of gut bacterial products into the bloodstream. These bacterial products can overstimulate the immune system leading to increased inflammation and HIV disease progression. The investigators will investigate whether oral supplementation of certain beneficial "probiotic" bacteria may attenuate these processes in HIV infected women in Mali, Africa.

This is a single arm study to evaluate the effect of 12 weeks of combination oral probiotic supplementation (VSL#3, Sigma-Tau Pharmaceuticals - containing 9 × 1011 bacteria of 8 species: S. thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus paracasei, and Lactobacillus bulgaricus) on plasma biomarkers of immune cell activation, and inflammation. The study population will be 50 chronically HIV-infected but generally healthy, non-pregnant, Malian women subjects with CD4+ T-cell count ≥ 350 cells/mm3 who are not receiving antiretroviral therapy. Blood plasma/serum and fecal sampling will occur at baseline, 4, and 12 week as well as at 24 weeks. At these time points, probiotic will be dispensed, a medical history will be obtained, and adherence will be assessed. Prior to study entry, subjects will have eligibility and safety labs will be obtained and detailed baseline medical and symptom histories, demographics, weight, and stool frequency information will be recorded. A stress assessment questionnaire will be completed at baseline and week 12 to determine the effect of this intervention on stress levels.

The primary study outcome is to assess change (baseline to 12 week) in plasma soluble CD14 (a marker of monocyte response to bacterial endotoxin which has been associated with mortality) with study probiotic. Other outcomes will include assessing change (baseline to 12 week) in plasma interleukin-6, soluble CD163 (another monocyte activation marker), d-dimer (a marker of coagulopathy), intestinal fatty acid binding protein (a marker of gut epithelial cell injury) and fecal calprotectin (a marker of gut inflammation), as well as CD4+ T-cell counts, self reported stool quality (using the Bristol Stool Scale), safety and tolerability of the VSL#3 probiotic, and level of stress.

Conditions

• HIV

Interventions

OTHER

VSL#3® probiotic

Other: VSL#3® probiotic VSL#3® DS (Sigma-Tau Pharmaceuticals) is a well characterized water soluble, live (9 × 1011 bacteria/sachet), lyophilized preparation of 8 probiotic bacterium that have been detailed previously. Subjects will take 1 sachet of powder orally daily for 12 weeks. As many Malian homes lack refrigeration, subjects will be issued a special "canari", a commonly used earthenware water container also containing sand that works on the principal of "trans-evaporation" to keep contents at room temperature (\~24°C) even in warmer climates. We have verified this in country. Probiotics will be placed in a sealed plastic bag within a sealed jar in the sand of the canari. At the research site, probiotics will be kept refrigerated (4-8°C) in a study provided refrigerator

Sponsors & Collaborators

• Bill and Melinda Gates Foundation

  collaborator OTHER

• Virginia Commonwealth University

  lead OTHER

Principal Investigators

• Daniel E Nixon, DO, PhD · Virginia Commonwealth University, USA

• Saba Masho, MD, MPH · Virginia Commonwealth University, USA

• Susan Kornstein, MD · Virginia Commonwealth University, USA

Study Design

Allocation

NA

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-05-31

Primary Completion

2016-03-31

Completion

2016-03-31

Countries

• Mali

Study Locations