Probiotic Visbiome for Inflammation and Translocation in HIV Ι

Study Overview
=================
Brief Summary
-----------------
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 common among people living with HIV, 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 antiretroviral therapy (ART) will improve gut CD4 T cell restoration and function and therefore reduce microbial translocation and immune activation. 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 a phenotype that is associated with reduce inflammation, and Visbiome was also protective in a non-human primate model of SIV infection. Therefore, we believe that the beneficial bacteria from Visbiome will accelerate the normalization of gut immune cells and function in HIV-infected individuals as they start ART. Early resolution of gut immune cells may normalize microbial translocation and immune activation and will reduce the rates of HIV-associated comorbidities.

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

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: Visbiome
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented HIV-1 infection Male adult (age >18 years) Antiretroviral therapy-naïve Ability to provide informed consent HIV-1 viral load ≥1,000 copies/ml Exclusion Criteria: Current alcohol or substance use judged by the Investigator to potentially interfere with participant 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 Malignancy 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
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 experimental 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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood immune activation | Percent of blood immune activation (coexpression of CD38 and HLA-DR) on CD8 T cells at week 24 in participants randomized to probiotic Visbiome versus the placebo arm | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of microbial translocation (including LPS and sCD14) |  | 24 weeks | 
| Plasma level of inflammation and coagulation (including IL-6, D-dimer and CRP) |  | 24 weeks | 
| Number and function of gut immune cells (including CD4 T cell subsets) |  | 24 weeks | 
| Intestinal permeability (Lac/Mac ratio) |  | 24 weeks | 
| Microbiome analysis by 16s rRNA bacterial DNA isolated from gut tissue and anal swabs |  | 24 weeks | 
| Gut HIV DNA levels |  | 24 weeks | 
| Canadian Diet History Questionnaire |  | 24 weeks | 
| Safety assessed by AE monitoring and participant questionnaire |  | 24 weeks | 
| Tolerability of Visbiome assessed by AE monitoring and participant questionnaire |  | 24 weeks | 
| Adherence to probiotic Visbiome assessed by participant questionnaire and sachet count |  | 24 weeks |