Adipose Tissue and Immune Activation in HIV

Summary

The prevalence of HIV-associated wasting declined dramatically with the introduction of effective antiretroviral therapy (ART), but as patients survive longer on treatment the proportion of overweight (body mass index \[BMI\] \>25 kg/m2) and obese (BMI \>30 kg/m2) HIV-infected individuals has been rising over time and is reaching parity with the general population. Adipose tissue has broad effects on immune function relevant to HIV infection, including the basal inflammatory state and peripheral lymphocyte populations, but there are few data on the effects of high adiposity on HIV immunology. This issue is directly relevant to promoting the long-term health of ART-treated individuals, many of which can now survive for decades on treatment, as emerging evidence suggests that increased immune activation is a major risk factor for the development of cardiovascular and metabolic diseases in this population. HIV-infected individuals on ART have an approximately 2-fold higher risk of myocardial infarction and a 4-fold higher risk of type 2 diabetes mellitus, and the proportion of deaths among HIV-infected individuals due to non-AIDS conditions now exceeds those due to AIDS.

Despite the increasing proportion of overweight and obese HIV-infected persons, few prior studies have investigated the interaction between adipose tissue, immune activation, and risk factors for cardiovascular and metabolic disease in treated HIV. The overall goal of this study is to understand the complex relationships between adipose tissue, innate and cellular immune activation, and metabolic and cardiovascular disease risk factors in persons on long-term antiretroviral therapy. To this end, we will use an observational, cross-sectional cohort design to compare in vivo markers of immune activation, ex vivo cytokine expression, and metabolic and cardiovascular disease markers in HIV-infected individuals with a range of body composition profiles and between overweight/obese HIV-infected and uninfected individuals.

Conditions

• Human Immunodeficiency Virus
• Obesity

Interventions

RADIATION

dual-energy X-ray absorptiometry (DEXA) scan

Whole body dual-energy X-ray absorptiometry (DEXA) scan to assess lean and fat mass

OTHER

Carotid and branchial artery ultrasound

Ultrasound to assess carotid plaque and brachial artery flow mediated dilation

DIAGNOSTIC_TEST

2-hour oral glucose tolerace test

Ingestion of 75g of glucose syrup with blood collection for glucose and insulin at time 0, 90min and 120min

DIAGNOSTIC_TEST

Blood collection

Blood collection for measurement of circulating proteins (cytokines) and isolation of immune cells

Sponsors & Collaborators

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• John Koethe, MD · Vanderbilt University Medical Center

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-04-12

Primary Completion

2014-11-03

Completion

2020-02-15

Countries

• United States

Study Locations