Gut Microbiota Changes of HIV Patients Before and After One Year of ART

Study Overview
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Brief Summary
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HIV infection leads to destruction of CD4+T cells in the gut-associated lymphoid tissue (GALT) and promotes a decline in mechanical barrier functions of the gut mucosa, and the subsequent translocation of microbial products from the gastrointestinal tract to systemic circulation. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Many studies have revealed strong and characteristic compositional differences in gut microbiota between individuals with HIV infection and seronegative controls. So far, several probiotic organisms have shown the ability to enhance intestinal epithelial barrier functions, reduce inflammation, and support effective Th-1 responses. Probiotics mainly stimulates polymeric IgA secretion, avoid bacterial overgrowth and their translocation, and produce a self-limited inflammatory response through development of regulatory T (Treg) cells by anti-inflammatory cytokine production. Therefore, we design a prospective, randomized, double-blind, placebo-controlled study to determine whether the use of a probiotic can expand beneficial microbiota that aid in decreasing bacterial translocation and pro-inflammatory cytokine production, thereby improving immune functions in HIV-infected subjects. Participants in the intervention group will receive oral probiotic containing 3 billion Bifidobacterium and 1 billion Lactobacillus once daily, while those in the placebo group will take placebo which contains no probiotic but has the same flavor and characteristics as the probiotic product.. Gut bacterial community diversity and composition, immune recovery and activation in peripheral plasma, plasma levels of gut damage, microbial translocation and inflammation at baseline and after 12 months of receiving intervention will be analyzed.

Official Title
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Effect of 1-year Antiretroviral Treatment on Gut Microbiota Diversity and Composition in Treatment-naïve HIV-infected Chinese Individuals

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Antiretroviral Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old; Documented HIV infection; No history of gastrointestinal diseases; Good adherence and promise to follow-up; Ability to provide informed consent. 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
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All participants<br>All enrolled participants in this study | Drug: Antiretroviral Therapy<br>* All participants receive antiretroviral therapy to control virus replication and restore CD4+ T-cell count.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut bacterial community diversity and composition | Microbiota profiling are performed on fecal samples from each subjects, and 8-10 participants receive gastrointestinal endoscope according to their willingness | Change from baseline to 1 year after antiretroviral therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute CD4+ T-cell and CD8+ T-cell counts in peripheral plasma | CD4+ and CD8+ T cells are analyzed by flow cytometry | Change from baseline to 1 year after antiretroviral therapy | 
| The level of T cell activation and different immunophenotype in peripheral plasma | CD38+HLA-DR+, CD8+CD28+ T cell subsets are analyzed by flow cytometry | Change from baseline to 1 year after antiretroviral therapy | 
| Plasma levels of inflammation and coagulation markers | Levels of IL-8, IL-1β, IL-6, CRP, TNF-α and D-dimer | Change from baseline to 1 year after antiretroviral therapy | 
| Plasma levels of microbial translocation and monocyte activation markers | Levels of I-FABP, LPS, LBP, sCD14, sCD40L, and IDO | Change from baseline to 1 year after antiretroviral therapy | 
| Metabolic measurements from blood plasma | Levels of vitamin D, glucose and insulin, and lipid profiling | Change from baseline to 1 year after antiretroviral therapy | 
| Feasibility, safety, tolerability, adherence, and acceptability of study product and procedures | Based on patients' description and intervention-related adverse events | Change from baseline to 1 year after antiretroviral therapy | 
| HIV RNA | HIV-RNA is detected by Roche assay with the limit of 20 copies/mL | Change from baseline to 1 year after antiretroviral therapy |