Probiotic Supplementation for Those Immune Non-responders With HIV-1 Infection

Study Overview
=================
Brief Summary
-----------------
Gut bacterial community diversity and composition, immune recovery and activation in peripheral plasma/mucosa, plasma levels of gut damage, microbial translocation and inflammation at baseline and after 6 months of receiving intervention will be analyzed.

Detailed Description
-----------------
Up to 25% of HIV-infected individuals receiving antiretroviral treatment demonstrate suboptimal blood cluster of differentiation 4（CD4） recovery despite effective viral suppression; this immunologic non-responder (INR) phenotype is associated with increased immune activation and with higher rates of AIDS and non-AIDS related conditions, and death. Poor gut integrity, increased microbial translocation, and reduced CD4 T-cell trafficking to the gut could be a source of ongoing inflammation in INR individuals. Researches have shown that the gut microbiota compositions are different in INRs and immunological responders (IRs). Probiotics, by modulation of gut microbiota, can help induce epithelial healing and prevent bacterial translocation. Probiotic supplementation, therefore, may be a nutritional target for INRs by boosting CD4 cell counts. We design a prospective, case-control, self-contrast study to explore the efficacy and safety of probiotic supplementation in INRs. Participants will receive oral probiotic containing 3 billion Bifidobacterium and 1 billion Lactobacillus once daily. Gut bacterial community diversity and composition, immune recovery and activation in peripheral plasma/mucosa, plasma levels of gut damage, microbial translocation and inflammation at baseline and after 6 months of receiving intervention will be analyzed.

Official Title
-----------------
Effect and Safety of Probiotic Supplementation in Immune Non-responders With HIV-1 Infection

Conditions
-----------------
HIV-infection/Aids

Intervention / Treatment
-----------------
* Dietary Supplement: Bifidobacteria and Lactobacilli triple viable capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented HIV-1 infection 18-65 years old On antiretroviral therapy (>2 years) Ability to provide informed consent Undetectable plasma HIV-1 viral load for the past 2 years CD4 T-cell count <350/mm3 for the last 2 years No history of gastrointestinal diseases Exclusion Criteria: Administration of antibiotics, probiotics, or prebiotics or experience of diarrhea within the previous 3 months; Administration of anti-inflammatory drugs, corticosteroids, immunosuppressive drugs, immunomodulator within the previous 3 months; Severe organ dysfunction Pregnancy or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INR(oral probiotic capsules containing 3 billion Bifidobacterium and 1 billion Lactobacillus)<br>Participants will receive oral probiotic capsules containing 3 billion Bifidobacterium and 1 billion Lactobacillus once daily for 6 months. | Dietary Supplement: Bifidobacteria and Lactobacilli triple viable capsules<br>* Bifidobacteria and Lactobacilli triple viable capsules (provided by Shenzhen Wan he Pharmaceutical Co., Ltd., China) are bilayer mini pellets and are resistant to gastric acid. So Bifidobacterium billion Lactobacillus can only be released in intestine. Participants will take 1.27g (contain 3 billion Bifidobacterium and 1 billion Lactobacillus) once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune recovery and activation | CD4+ T-cell and cluster of differentiation 8（CD8）+ T-cell counts, CD4/CD8 ratio, cluster of differentiation 38（CD38）+/ human leukocyte antigen(HLA）-HLA class II(DR)+ CD8+/CD4+ T cell ratio | Changes from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of gut damage, microbial translocation and inflammation | interleukin(IL)-8, IL-1β, IL-6, tumor necrosis factor(TNF)-α, C reactive protein(CRP), D-dimer, Intestinal fatty aid binding protein(I-FABP), lipopolysaccharide(LPS) , lipopolysaccharide-binding protein(LBP), sCD14, sCD40L, and Kynurenine/Tryptophan ratio | Changes from baseline to 6 months | 
| Blood viral load | HIV-RNA | Changes from baseline to 6 months | 
| Metabolic measurements from blood plasma | Vitamin D, glucose and insulin, and lipid profiling | Changes from baseline to 6 months | 
| Feasibility, safety, tolerability, adherence, and acceptability of study product and procedures | Based on patients' description and intervention-related adverse events | Changes from baseline to 6 months | 
| Gut bacterial community diversity and composition | Bacterial community diversity and composition determined by 16S ribosomal ribonucleic acid(rRNA) gene sequencing of fecal samples | Changes from baseline to 6 months |