A Double Mask Randomized Placebo- Controlled Trial of Probiotics to - - PowerPoint PPT Presentation

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Dec 27, 2023 239 likes •319 views

A Double Mask Randomized Placebo- Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Youth A multi-center clinical trial sponsored by the Adolescent Trials Network (NICHD) Protocol Chairs- John

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A Double Mask Randomized Placebo- Controlled Trial of Probiotics to Lower Microbial Translocation and Immune Activation in HIV-Infected Youth

A multi-center clinical trial sponsored by the Adolescent Trials Network (NICHD) Protocol Chairs- John Sleasman and Grace Aldrovandi

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Altered GIT fuels immune activation

Mayhem that occurs to mucosal

surfaces after acute infection damages immunological and structural GI barrier allowing intestinal microbial products to cross over to the “other side”

Systemic microbes and microbial

products stimulate the adaptive and innate immune systems and exacerbate immune activation

– Microbial translocation

Brenchley et al Nat Immunol 2006

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Postulated role for probiotics on MT and induction of immune tolerance in the GI track Science, 307, 1920 (2005)

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STUDY POPULATION

HIV-infected youth 13-24 years of age inclusive
Acquired HIV infection > 10 years of age
Absolute CD4 T-cell count > 350 cells/ul
Cohort 1: Not receiving ART with HIV-1

plasma RNA < 50,000 copies/ml

Cohort 2: Currently receiving ART (>24 weeks)

prior to entry and quantitative HIV-1 plasma RNA < 400 copies/ml

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PRIMARY OBJECTIVE

To determine if once daily probiotics

(L plantarum 299/299v) decreases microbial translocation in HIV-infected youth based on changes in plasma LPS.

Sample size: 80 subjects (Cohort 1 = 40,

Cohort 2 = 40)

Study Duration: 24 weeks on intervention, 32

weeks on study.

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Secondary Objectives

Quantify extent that L plantarum with fecal

samples over time

Evaluate impact of probiotics on plasma pro-

inflammatory cytokines levels and extent of Macrophage and T cell activation

Examine effect of probiotics HIV-1 plasma viral

load and CD4 T-cell subsets

Molecularly characterize changes in overall

bacteria diversity within the stool specimens fro youth treated with probiotics

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Barriers

Identification of effective probiotic likely to

colonize the GI tract

Developing CTA/MTA with foreign company
Shifting guidance from FDA regarding the use
f probiotics in clinical trials