The HIV, Adipose Tissue Immunology, and Metabolism Study (HATIM)

May 1, 2026 updated by: John R. Koethe, Vanderbilt University Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

With the introduction of effective antiretroviral therapy (ART), HIV-infected persons can now survive for decades, but this success has been accompanied by an increased risk of developing metabolic disease compared HIV-negative persons. In the Multicenter AIDS Cohort Study, HIV-infected men had a greater than 4-fold increased incidence of a new diabetes diagnosis compared to HIV-negative men after adjusting for age and body mass index (BMI). Prevalence studies of diabetes in HIV-infected individuals on ART have reported incidence rates of 3.1 to 14 per 1000 patient-years. Furthermore, treated HIV infection appears to act synergistically with other risk factors, and diabetes prevalence is especially high among HIV-infected individuals with high BMI and advanced age.

Recent studies from HIV-negative subjects identified several associations between adaptive immune cell populations and impaired glucose tolerance. Peripheral T regulatory (Treg) cells are significantly lower in patients with type-2 diabetes , while the numbers activated T cells, CD4+ TH1 (pro-inflammatory) cells, and memory CD4+ T cells are higher in diabetics.

Immune cells translocate from the circulation into adipose tissue in a dynamic process, and T cells are present in the stromal fraction of adipose tissue and affect adipocyte function. The striking increase in adipose tissue CD4+ TH1 cells and CD8+ T cells, and a decrease in Treg cells, observed in obesity may have an important role in the development of insulin resistance. Secretion of the proinflammatory cytokines interferon-γ and interleukin (IL)-17 by TH1 and TH17 cells are implicated in the induction of proinflammatory M1 macrophages, which express IL-6 and tumor necrosis factor alpha, and inhibit adipocyte insulin signaling by promoting phosphorylation of insulin receptor substrate 1. The investigators hypothesize that the chronic, HIV-related activation of circulating CD4+ and CD8+ T cells may be accompanied by the accumulation of activated T cells in adipose tissue with adverse effects on metabolic activity.

In this study, the investigators will test the hypothesis that the oligoclonal expansion of chronically activated peripheral T cells in adipose tissue is a primary driver of macrophage inflammation and reduced adipocyte insulin sensitivity. Furthermore, the investigators propose that this represents a central mechanistic linkage underlying the association between circulating T cell activation and incident diabetes risk observed in HIV-infected and HIV-negative individuals.

Study Type

Observational

Enrollment (Actual)

172

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37209
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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

Description

HIV+ Participants:

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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:

Inclusion Criteria:

  • 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)

Exclusion criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HIV+ non-diabetics
HIV-infected participants with hemoglobin A1c (HbA1c) <5.7% or fasting glucose <100 mg/dl.
Procedure: Subcutaneous adipose tissue biopsy
Percutaneous adipose tissue biopsy
Radiation: CT scan
CT scan of chest and abdomen without contrast
Diagnostic test: Oral glucose tolerance 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.
Diagnostic test: Blood collection
Fasting blood collection for plasma cytokines and T cell phenotypes.
HIV+ pre-diabetics
HIV-infected participants with HbA1c 5.7-6.4% or fasting glucose 100-125 mg/dl.
Procedure: Subcutaneous adipose tissue biopsy
Percutaneous adipose tissue biopsy
Radiation: CT scan
CT scan of chest and abdomen without contrast
Diagnostic test: Oral glucose tolerance 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.
Diagnostic test: Blood collection
Fasting blood collection for plasma cytokines and T cell phenotypes.
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
Percutaneous adipose tissue biopsy
Radiation: CT scan
CT scan of chest and abdomen without contrast
Diagnostic test: Blood collection
Fasting blood collection for plasma cytokines and T cell phenotypes.
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
Percutaneous adipose tissue biopsy
Radiation: CT scan
CT scan of chest and abdomen without contrast
Diagnostic test: Blood collection
Fasting blood collection for plasma cytokines and T cell phenotypes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adipose tissue T cell surface marker phenotype and antigen receptor sequence
Time Frame: At study enrollment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
CT measurements of visceral, hepatic, and pericardial fat content
Time Frame: At study enrollment
Quantification of visceral, hepatic, and pericardial adipose tissue content, compared by HIV and diabetes status
At study enrollment
Circulating T cell surface marker phenotype
Time Frame: At study enrollment
Flow cytometry measurement of circulating T cell surface marker phenotypes, compared by HIV and diabetes status
At study enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: John Koethe, MD, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2017

Primary Completion (Actual)

March 13, 2020

Study Completion (Actual)

May 1, 2026

Study Registration Dates

First Submitted

June 16, 2020

First Submitted That Met QC Criteria

June 25, 2020

First Posted (Actual)

June 30, 2020

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 161254

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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