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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Antiretroviral Therapy

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients were recruited from the Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China. All participants are Chinese and meet eligibility criteria.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
All participants; All enrolled participants in this study	Drug: Antiretroviral Therapy; All participants receive antiretroviral therapy to control virus replication and restore CD4+ T-cell count.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Wei LYU, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents; Anti-Retroviral Agents
• Other Study ID Numbers: CACTGUT18A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No