Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients.

This study plans to learn more about immune responses in intestinal (gut) tissue in people with human immunodeficiency virus (HIV) infection. This study will determine whether change in the composition of gut bacteria in HIV infected individuals is related to a high prevalence of chronic gut inflammation and metabolic disease. The investigators will also investigate immune-modulatory properties of specific bacteria that correlate with disease both by characterizing which functional genes are selected for in their genomes and by stimulating immune cells isolated from blood and gut tissue with bacterial isolates. This work will establish whether gain/loss of bacterial drivers/suppressors of information in the gut contributes to metabolic disease in HIV-infected individuals.

Study Overview

• Status: Completed
• Conditions: HIV; Lipodystrophy

Detailed Description

This is a prospective cohort and cross-sectional case-control study. Study participation will last up to 2 months and 93 participants will be enrolled. Participants will be evaluated for lipodystrophy, asked to complete food & gastrointestinal symptoms questionnaires and provide stool samples. A subset of participants will be asked to have a flexible sigmoidoscopy (mucosal biopsy).

Cohort A will consist of 93 participants:

Cohort A1: ART (Antiretroviral therapy) -treated HIV-infected individuals with lipodystrophy (n=35) Cohort A2: ART-treated HIV-infected individuals without lipodystrophy (n=18) Cohort A3: HIV-1 infected individuals naïve to ART (n=20) Cohort A4: HIV-1 seronegative individuals who are at a high risk for infection (n=20)

Cohort B will be a selected subset of subjects from Cohort A:

Cohort B1: ART-treated HIV-infected individuals with HIV-associated dysbiosis (n=10) Cohort B2: ART-treated HIV-infected individuals without HIV-associated dysbiosis (n=10)

• Study Type: Observational
• Enrollment (Actual): 93

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV positive and HIV negative subjects (with and without lipodystrophy) between 18 and 65 years old.

Description

Inclusion Criteria:

• Men and women; 18 years to 65 years (All Cohorts)
• Subjects with chronic HIV-1 Infection defined as a positive ELISA confirmed by a positive Western Blot or plasma HIV-1 RNA level >1,000 copies/mL at any time in the past. (Cohorts A1, A2 & A3)
• HIV-1 seronegative (Cohort A4)
• Either with or without lipodystrophy (to be assessed at Visit 1)
• Body mass index (BMI) between 21-29 mg/kg2 and weight stable for at least 3 months (All Cohorts)
• Antiretroviral therapy (ART) naïve (Cohort A3): <10 days of ART treatment at any time prior to Visit 1 or previously on ART but off treatment for the previous 6 months prior to Visit 1
• Long-term ART (Cohort A1 & A2): Must be on same antiretroviral treatment and have a plasma HIV-1 RNA <25 copies/mL for 3-6 months prior to Visit 1.Liver function tests not greater than 2x normal, normal kidney and thyroid function. Fasting glucose must be <110 mg/dl
• Liver function tests not greater than 2x normal, normal kidney and thyroid function. Fasting glucose must be <110 mg/dl
• ART-treated individuals whose microbiota resembles those with untreated HIV infection and ART-treated individuals whose microbiota resembles the HIV-negative control cohort (equal numbers with and without lipodystrophy).(Cohort B; a subset of Cohort A)

Exclusion Criteria:

• Gastrointestinal disease such as inflammatory bowel disease, Clostridium difficile colitis or celiac sprue.
• history of bowel resection, bleeding disorder, history of hyperglycemia, treated with high-dose glucocorticoid therapy or alpha-interferon in past year Current use of anticoagulant therapy
• Daily use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) with inability to withhold drug for 7 days before and after a rectosigmoid biopsy procedure.
• Used antibiotics within the prior three months
• Pregnancy
• Current use of proton pump inhibitors and H2-blockers
• Active opportunistic or other chronic infection, such as hepatitis B or C or an active malignancy
• Patient inability to participate in the study, such as inability to undergo venipuncture, completion of questionnaire or mucosal biopsy (if selected) procedures that form part of the inclusion/exclusion criteria or part of the outcome measure.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
Cohort A1; ART-treated HIV-infected individuals with lipodystrophy
Cohort A2; ART-treated HIV-infected individuals without lipodystrophy
Cohort A3; HIV-1 infected individuals naïve to ART
Cohort A4; HIV-1 seronegative individuals who are at a high risk for infection
Cohort B1; A subset of subjects from Cohort A: ART-treated HIV-infected individuals with HIV-associated dysbiosis
Cohort B2; A subset of subjects from Cohort A: ART-treated HIV-infected individuals without HIV-associated dysbiosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the gut microbiota composition using 16S ribosomal RNA (rRNA) sequencing of fecal samples	Compare the gut microbiota composition of HIV-positive subjects with and without lipodystrophy and long-term ART, and HIV-negative controls with diet and metabolic and immune activation markers in blood.	2 months
Determine of gut microbiota composition using rectosigmoid biopsy tissue	Compare the gut microbiota composition of HIV-positive ART-treated individuals by CD4+ populations and immune activation markers in gut-associated lymphoid tissues (GALT)	2 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Catherine Lozupone, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 7, 2014

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Gut microbiota composition
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Metabolic Diseases; Lipodystrophy; Dysbiosis
• Other Study ID Numbers: 14-1595