HIV-1 Infection
Conditions
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.
Interventions
DRUGVisbiome
Visbiome probiotic
OTHERPlacebo
Placebo
Sponsors
CIHR Canadian HIV Trials Network
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood immune activation | 24 weeks | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Level of microbial translocation (including LPS and sCD14) | 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 |
| Gut HIV DNA levels | 24 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety (open-label) assessed by AE monitoring and participant questionnaire | 48 weeks | — |
| Metabolomic measurements: vitamin D levels, glucose measurements, insulin levels and lipid profiling | 24 weeks | — |
| Adherence to probiotic Visbiome (open-label) assessed by participant questionnaire and sachet count | 48 weeks | — |
| Tolerability of Visbiome (open-label) assessed by AE monitoring and participant questionnaire | 48 weeks | — |
| Bacterial community diversity, determined by 16s rRNA gene sequencing of penile swabs | 24 weeks | — |
| Bacterial community composition, determined by 16s rRNA gene sequencing of penile swabs | 24 weeks | — |
| Blood immune activation (open-label) | 48 weeks | 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 |
| Level of microbial translocation (including LPS and sCD14) (open-label) | 48 weeks | — |
| Plasma levels of inflammation and coagulation (including IL-6, D-dimer and CRP) (open-label) | 48 weeks | — |
| Number and function of gut immune cells (including CD4 T cell subsets) (open-label) | 48 weeks | — |
| Intestinal permeability (Lac/Man) (open-label) | 48 weeks | — |
| Microbiome analysis by 16s rRNA bacterial DNA isolated from penile swabs (open-label) | 48 weeks | — |
| Gut HIV DNA levels (open-label) | 48 weeks | — |
| Canadian Diet History Questionnaire (open-label) | 48 weeks | — |
Countries
Canada
Outcome results
None listed