Adipose Tissue and Immune Activation in HIV

NCT04439448 | Completed

• 1 other identifier: K23AI100700
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (2)

• CD38+ CD4+ T cells

  Flow cytometry measurement of CD38 expression on isolated CD4+ T cells

  At study enrollment

• Plasma interleukin-6

  Level of circulating interleukin-6

  At study enrollment

Secondary Outcomes (3)

• Carotid intima media thickness

  At study enrollment

• Brachial artery maximal flow mediated dilation

  At study enrollment

• Visceral adipose tissue volume (cm3)

  At study enrollment

Study Arms (3)

HIV+ non-obese

HIV+ adults on antiretroviral therapy with a body mass index \<30 kg/m2

Radiation: dual-energy X-ray absorptiometry (DEXA) scan; Other: Carotid and branchial artery ultrasound; Diagnostic Test: 2-hour oral glucose tolerace test; Diagnostic Test: Blood collection

HIV+ obese

HIV+ adults on antiretroviral therapy with a body mass index \>=30 kg/m2

Radiation: dual-energy X-ray absorptiometry (DEXA) scan; Other: Carotid and branchial artery ultrasound; Diagnostic Test: 2-hour oral glucose tolerace test; Diagnostic Test: Blood collection

HIV-negative obese

HIV-negative adults on antiretroviral therapy with a body mass index \>=30 kg/m2

Radiation: dual-energy X-ray absorptiometry (DEXA) scan; Other: Carotid and branchial artery ultrasound; Diagnostic Test: 2-hour oral glucose tolerace test; Diagnostic Test: Blood collection

Interventions

dual-energy X-ray absorptiometry (DEXA) scan RADIATION

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

HIV+ non-obese; HIV+ obese; HIV-negative obese

Carotid and branchial artery ultrasound OTHER

Ultrasound to assess carotid plaque and brachial artery flow mediated dilation

HIV+ non-obese; HIV+ obese; HIV-negative obese

2-hour oral glucose tolerace test DIAGNOSTIC_TEST

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

HIV+ non-obese; HIV+ obese; HIV-negative obese

Blood collection DIAGNOSTIC_TEST

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

HIV+ non-obese; HIV+ obese; HIV-negative obese

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

Health persons with HIV receiving care at the Vanderbilt Comprehensive Care Clinic and healthy persons without HIV receiving care at Vanderbilt University Medical Center

You may qualify if:

• age \>18 years
• on ART \>2 years
• a CD4+ nadir \>100 cells/µl prior to starting ART
• a CD4 \>350 cells/µl at the time of enrollment
• HIV-1 viral load \<50 copies/ml
• Pre-menopausal

You may not qualify if:

• Pregnant (women only)
• Current use of anti-diabetic medications or statins
• HIV uninfected participants:
• age \>18 years
• body mass index \>= 30 kg/m2
• Pre-menopausal
• Pregnant (women only)
• Current use of anti-diabetic medications or statins

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (5)

• Koethe JR, Jenkins CA, Furch BD, Lake JE, Barnett L, Hager CC, Smith R, Hulgan T, Shepherd BE, Kalams SA. Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2018 Sep 1;79(1):135-140. doi: 10.1097/QAI.0000000000001768.

  PMID: 29794823 RESULT

• Grome HN, Barnett L, Hagar CC, Harrison DG, Kalams SA, Koethe JR. Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV. AIDS Res Hum Retroviruses. 2017 Feb;33(2):181-186. doi: 10.1089/AID.2016.0113. Epub 2016 Sep 14.

  PMID: 27527002 RESULT

• Koethe JR, Jenkins CA, Petucci C, Culver J, Shepherd BE, Sterling TR. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy. Medicine (Baltimore). 2016 May;95(19):e3634. doi: 10.1097/MD.0000000000003634.

  PMID: 27175676 RESULT

• Koethe JR, Grome H, Jenkins CA, Kalams SA, Sterling TR. The metabolic and cardiovascular consequences of obesity in persons with HIV on long-term antiretroviral therapy. AIDS. 2016 Jan 2;30(1):83-91. doi: 10.1097/QAD.0000000000000893.

  PMID: 26418084 RESULT

• Masenga SK, Elijovich F, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, Mutale W, Munsaka SM, Zhao S, Koethe JR, Kirabo A. Elevated Eosinophils as a Feature of Inflammation Associated With Hypertension in Virally Suppressed People Living With HIV. J Am Heart Assoc. 2020 Feb 18;9(4):e011450. doi: 10.1161/JAHA.118.011450. Epub 2020 Feb 17.

  PMID: 32064996 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood mononuclear cells and plasma

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Obesity

Interventions

Absorptiometry, Photon; 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; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; 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: Associate Professor

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 19, 2020
• Study Start: April 12, 2013
• Primary Completion: November 3, 2014
• Study Completion: February 15, 2020
• Last Updated: June 19, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)