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

NCT02258685 | Completed

• 1 other identifier: 14-1595
• Study Type: observational
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV; Lipodystrophy

Keywords

Gut microbiota composition

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (6)

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and rectosigmoid biopsy tissue will be collected.

MeSH Terms

Conditions

Lipodystrophy

Condition Hierarchy (Ancestors)

Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Catherine Lozupone, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 7, 2014
• Study Start: November 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: July 1, 2019
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

US (1)