The HIV, Adipose Tissue Immunology, and Metabolism Study

NCT04451980 | Completed DMC

• 1 other identifier: 161254
• Study Type: observational
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

With the introduction of effective anti-retroviral therapy (ART), HIV-infected persons can now survive for decades, but this success has been accompanied by an increased risk of developing metabolic disease and diabetes in HIV-infected persons compared to the general population. Recent studies from HIV-negative subjects have identified several associations between circulating immune cell populations and impaired glucose tolerance, including increased activated CD4+ and CD8+ T cells, and reduced regulatory T cells. Of note, these same changes in peripheral T cell subsets are frequently observed in patients with chronic HIV infection. The goal of this study is to assess whether the circulating T cell distribution is reflective of the adipose tissue T cell distribution, and to understand whether chronic adipose tissue T cell activation may impair adipocyte (i.e., fat cell) function and insulin sensitivity. If the investigators' hypotheses are correct, this will demonstrate that chronic peripheral immune activation (i.e., high memory T cells, low naïve cells, and increased expression of activation surface markers) is associated with greater adipose-resident CD4+ and CD8+ T cell expression of activation markers, adipose tissue inflammation, and insulin resistance.

Conditions

Hiv; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Adipose tissue T cell surface marker phenotype and antigen receptor sequence

  Flow cytometry measurement of adipose tissue T cell surface marker phenotypes and sequencing of T cell receptors, compared by HIV and diabetes status

  At study enrollment

Secondary Outcomes (2)

• CT measurements of visceral, hepatic, and pericardial fat content

  At study enrollment

• Circulating T cell surface marker phenotype

  At study enrollment

Study Arms (4)

HIV+ non-diabetics

HIV-infected participants with hemoglobin A1c (HbA1c) \<5.7% or fasting glucose \<100 mg/dl.

Procedure: Subcutaneous adipose tissue biopsy; Radiation: CT scan; Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Blood collection

HIV+ pre-diabetics

HIV-infected participants with HbA1c 5.7-6.4% or fasting glucose 100-125 mg/dl.

Procedure: Subcutaneous adipose tissue biopsy; Radiation: CT scan; Diagnostic Test: Oral glucose tolerance test; Diagnostic Test: Blood collection

HIV+ diabetics

HIV-infected participants with HbA1c \>=6.5% or fasting glucose \>=126 mg/dl or on anti-diabetic medications.

Procedure: Subcutaneous adipose tissue biopsy; Radiation: CT scan; Diagnostic Test: Blood collection

HIV-negative diabetics

HIV-negative participants with HbA1c \>=6.5% or fasting glucose \>=126 mg/dl or on anti-diabetic medications.

Procedure: Subcutaneous adipose tissue biopsy; Radiation: CT scan; Diagnostic Test: Blood collection

Interventions

Subcutaneous adipose tissue biopsy PROCEDURE

Percutaneous adipose tissue biopsy

HIV+ diabetics; HIV+ non-diabetics; HIV+ pre-diabetics; HIV-negative diabetics

CT scan RADIATION

CT scan of chest and abdomen without contrast

HIV+ diabetics; HIV+ non-diabetics; HIV+ pre-diabetics; HIV-negative diabetics

Oral glucose tolerance test DIAGNOSTIC_TEST

Ingestion of 75g of oral glucose syrup and measurement of blood glucose and insulin at time 0, 15 min, 30 min, 60 min, 90 min, and 120 min.

HIV+ non-diabetics; HIV+ pre-diabetics

Blood collection DIAGNOSTIC_TEST

Fasting blood collection for plasma cytokines and T cell phenotypes.

HIV+ diabetics; HIV+ non-diabetics; HIV+ pre-diabetics; HIV-negative diabetics

Eligibility Criteria

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

Study Population

HIV-positive participants are recruited from the Vanderbilt Comprehensive Care Clinic, and HIV-negative participants are recruited from Vanderbilt University Medical Center clinics

You may qualify if:

• On antiretroviral therapy for at least 18 months
• HIV-1 RNA \<400 copies/ml for the prior 12 months
• CD4+ count \>350 cells/µl in the prior 12 months
• HbA1c in prior 6 months within specified limits (See Figure)
• Pre-menopausal by self-report or post-menopausal but not on hormone replacement therapy (HRT)

You may not qualify if:

• Known inflammatory or rheumatologic conditions
• Heavy alcohol (\>11 drinks per week) or cocaine, amphetamine, or illicit (non-prescribed) opiate abuse by self-report
• Current use of DPP-4 inhibitors.
• HIV-negative Participants:
• A HbA1c \>6.5% or a fasting glucose \>126mg/dl, or on anti-diabetic medications for at least 6 months
• Pre-menopausal by self-report or post-menopausal but not on hormone replacement therapy (HRT)
• Known inflammatory or rheumatologic conditions
• Heavy alcohol (\>11 drinks per week) or cocaine, amphetamine, or illicit (non-prescribed) opiate abuse by self-report
• Current use of DPP-4 inhibitors.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37209, United States

Location

Related Publications (5)

• Wanjalla CN, McDonnell WJ, Barnett L, Simmons JD, Furch BD, Lima MC, Woodward BO, Fan R, Fei Y, Baker PG, Ram R, Pilkinton MA, Mashayekhi M, Brown NJ, Mallal SA, Kalams SA, Koethe JR. Adipose Tissue in Persons With HIV Is Enriched for CD4+ T Effector Memory and T Effector Memory RA+ Cells, Which Show Higher CD69 Expression and CD57, CX3CR1, GPR56 Co-expression With Increasing Glucose Intolerance. Front Immunol. 2019 Mar 19;10:408. doi: 10.3389/fimmu.2019.00408. eCollection 2019.

  PMID: 30941121 RESULT

• Koethe JR, McDonnell W, Kennedy A, Abana CO, Pilkinton M, Setliff I, Georgiev I, Barnett L, Hager CC, Smith R, Kalams SA, Hasty A, Mallal S. Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons. J Acquir Immune Defic Syndr. 2018 Feb 1;77(2):e14-e21. doi: 10.1097/QAI.0000000000001573.

  PMID: 29040163 RESULT

• Bailin SS, Ma S, Perry AS, Terry JG, Carr JJ, Nair S, Silver HJ, Shi M, Mashayekhi M, Kropski JA, Ferguson JF, Wanjalla CN, Das SR, Shah R, Koethe JR, Gabriel CL. The Primacy of Adipose Tissue Gene Expression and Plasma Lipidome in Cardiometabolic Disease in Persons With HIV. J Infect Dis. 2025 Feb 20;231(2):e407-e418. doi: 10.1093/infdis/jiae532.

  PMID: 39657693 DERIVED

• Swartz AZ, Robles ME, Park S, Esfandiari H, Bradshaw M, Koethe JR, Silver HJ. Cardiometabolic Characteristics of Obesity Phenotypes in Persons With HIV. Open Forum Infect Dis. 2024 Jul 8;11(7):ofae376. doi: 10.1093/ofid/ofae376. eCollection 2024 Jul.

  PMID: 39035569 DERIVED

• Werede AT, Terry JG, Nair S, Temu TM, Shepherd BE, Bailin SS, Mashayekhi M, Gabriel CL, Lima M, Woodward BO, Hannah L, Mallal SA, Beckman JA, Li JZ, Fajnzylber J, Harrison DG, Carr JJ, Koethe JR, Wanjalla CN. Mean Coronary Cross-Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV. J Am Heart Assoc. 2022 Dec 6;11(23):e025768. doi: 10.1161/JAHA.122.025768. Epub 2022 Nov 16.

  PMID: 36382956 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Collection and retention of whole adipose tissue samples, adipose tissue stromal vascular fraction, peripheral blood mononuclear cells, and plasma.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Diabetes Mellitus, Type 2

Interventions

Glucose Tolerance Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Specimen Handling; Punctures; Surgical Procedures, Operative

Study Officials

• John Koethe, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Infectious Disease - Medicine

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 30, 2020
• Study Start: August 31, 2017
• Primary Completion: March 13, 2020
• Study Completion: May 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)