Treatment With Probiotics (Saccharomyces Boulardii) and Its Role in Bacterial Translocation and Immune Reconstitution in VIH Infection.

Study Overview
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Brief Summary
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Objectives: MAIN: To evaluate the parameters of microbial translocation after treatment with probiotics (Saccharomyces boulardii) in HIV+ patients and its role on immune reconstitution and the changes in gut microbiota composition. SECONDARY OBJECTIVES: 1) To analyze the progress of immune activity markers after the administration of probiotics. 2) To determine the improvement of CD4+ lymphocytes and HIV viral load in patients after taking probiotics. Methods: Design: A prospective randomized open controlled double-blinded trial, to be performed at a tertiary care hospital in Barcelona. Subjects: Chronic HIV infected patients. Sample size: 44 cases. They´ll be divided in 2 groups: (1) Patients with CD4 +> 400 cells / ml and undetectable viral load for more than two years (22 cases) and (2) Patients with immunodiscordancy, defined as patients with CD4 + T cells lower than 350 cells / ml despite 4-7 years of effective antiretroviral therapy. (22 cases). Intervention: Patients were randomized in 2 subgroups: (A) they´ll receive daily oral supplementation with S. boulardii for 3 months and (B) they ´ll receive placebo. Variables: bacterial lipopolisaccharide levels measured by the Lipid-Binding protein (LBP), parameters of immune activation in plasma (soluble CD14, IFN-Υ, TNF-Alpha, IL (interleukine)-2, IL-5, IL-6, IL-12)and gut microbiota composition prior to the use of probiotics (baseline), at 3 and 6 months. Immunological and clinical data. Outcome measures: quantification of bacterial translocation levels, markers of activity and immune recovery. Analysis: Comparison of variables before and after the intervention. The analysis will be performed by biological and immunological effectiveness.

Official Title
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Treatment With Probiotics (Saccharomyces Boulardii) and Its Role in Bacterial Translocation and Immune Reconstitution in VIH Infection.

Conditions
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HIV -1 Infection

Intervention / Treatment
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* Dietary Supplement: Probiotic.
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic HIV infection and viral load undetectable > two years with stable ART CD4> 400 cells / ml. Patients with chronic HIV infection and viral load undetectable> two years with stable ART CD4 <350 cells / ml. Inform consent signed. Aged between 18- No limit. Exclusion Criteria: Patients who receive or have received in the past 6 months food supplements containing probiotics. Patients who have received antibiotic treatment in the last two months Patients who are poor presupposes adherence to dietary supplements. Patients who have changed the TAR in the last three months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>A probiotic (Saccharomyces boulardii) 2 caps/ 8h for 12 weeks. | Dietary Supplement: Probiotic.<br> <br> |
| Placebo Comparator: Placebo<br>No active substance is given. | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate microbial translocation-Binding lipopolysaccharide Protein (LBP). |  | From randomisation to 6 months. | 
| To evaluate Gut microbiota composition. | Change in gut microbiota (454 pyrosequencing of fecal samples). | From randomisation to 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate Markers of immune activity: soluble CD14 (sCD14), interferon gamma (IFN-Υ), tumor necrosis factor (TNF), IL-6, Reactive C protein, D -dimer, fibrinogen. |  | From randomisation to 6 months. | 
| Analyse parameters that determine the immune status: CD4 + lymphocyte count, CD 8 + and HIV viral load. |  | From randomisation to 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotic, HIV, Microbial translocation, inflammation, microbiota composition