Probiotic Visbiome for Inflammation and Translocation in HIV II

Study Overview
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Brief Summary
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Modern antiretroviral therapy (ART) has transformed the clinical care and lived experience of HIV infection. However, increased rates of adverse health conditions that are related to immune activation, such as cardiovascular disease (CVD) and neurodegenerative disease in ART-treated individuals persist. An important cause of this inflammation is the gut CD4 T cell loss and the leaking or translocation of luminal gut bacteria and other microbes across the bowel wall and into the bloodstream. The use of complementary and alternative therapies is very common among people living with HIV, with estimates ranging from 16-60%. However, their efficacy has generally not been well demonstrated. Probiotics are live microbes that may provide a health benefit to the host and the investigators believe that the simultaneous use of probiotics along with ART will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation. A major challenge to HIV treatment is the suboptimal CD4 T cell count despite successful HIV suppression on ART in immunologic non-responders (INRs). These individuals are at increased risk of AIDS-related deaths and non-AIDS related comorbidities that may be associated with increased immune activation and microbial translocation from the gut mucosa. With limited treatment options, alternative therapies to reduce inflammation and restore gut immunology will be important. Probiotic Visbiome consists of a high potency blend of eight different probiotics. The precise mechanism of action of Visbiome is unknown,but preclinical studies have shown that Visbiome may modulate the immune response towards an immunoregualtory phenotype with increased the levels of IL-10 and reduced levels of proinflammatory cytokines (TNFα, IL1β and IL-8). Therefore,the investigators believe that the beneficial bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected INRs. It is hypothesized consumption of Visbiome for 48 weeks will help restore the immune system in INRs who have suboptimal immune reconstitution to currently available ART. Resolution of gut immune cells will mean that microbial translocation and immune activation will be normalized and will reduce the rates of HIV-associated comorbidities.

Official Title
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Probiotic Visbiome for Inflammation and Translocation in HIV II (PROOV IT II)

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Visbiome
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HIV-1 infection Male adult (age >18 years) Currently on ART (>2 years but <10 years) Undetectable HIV-1 viral load <50 copies/ml for the past 2 years (1 viral blip below 500 copies/ml permitted in the past year) Last CD4 count <350 cells/μl, and >70% over the past 2 years <350 cells/μl Ability to provide informed consent Exclusion Criteria: Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance Taking pharmaceutical-grade probiotics Any of the following abnormal laboratory results in screening: Hemoglobin <85 g/L Neutrophil count <750 cells/μl Platelet count <50,000 cells/μL AST or ALT >5X the upper limit of normal Colitis Liver fibrosis (decompensated cirrhosis), portal hypertension or clinical hepatitis Other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Male

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Group<br>Visbiome probiotic group (900 billion bacteria daily; 2 sachets daily) | Drug: Visbiome<br>* Visbiome probiotic<br>|
| Placebo Comparator: Placebo Group<br>Placebo comparator group | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in blood immune activation | Percent change in blood immune activation (co-expression of CD38 and HLA-DR) on CD8 T cells at week 48 in participants randomized to probiotic Visbiome versus the placebo arm | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of microbial translocation (including LSP and sCD14) |  | 48 weeks | 
| Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP) |  | 48 weeks | 
| Number and function of gut immune cells (including CD4 T cell subsets) |  | 48 weeks | 
| Intestinal permeability (Lac/Mac ratio) |  | 48 weeks | 
| Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs |  | 48 weeks | 
| Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs |  | 48 weeks | 
| Gut HIV DNA levels |  | 48 weeks | 
| Canadian Diet History Questionnaire |  | 48 weeks | 
| Safety assessed by AE monitoring and participant questionnaire |  | 48 weeks | 
| Tolerability of Visbiome assessed by AE monitoring and participant questionnaire |  | 48 weeks | 
| Adherence to Visbiome assessed by participant questionnaire and sachet count |  | 48 weeks |