<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04439448</url>
  </required_header>
  <id_info>
    <org_study_id>K23AI100700</org_study_id>
    <nct_id>NCT04439448</nct_id>
  </id_info>
  <brief_title>Adipose Tissue and Immune Activation in HIV</brief_title>
  <acronym>AIAC</acronym>
  <official_title>An Observational Cohort Study of Adipose Tissue and Immune Activation in Treated HIV Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of HIV-associated wasting declined dramatically with the introduction of&#xD;
      effective antiretroviral therapy (ART), but as patients survive longer on treatment the&#xD;
      proportion of overweight (body mass index [BMI] &gt;25 kg/m2) and obese (BMI &gt;30 kg/m2)&#xD;
      HIV-infected individuals has been rising over time and is reaching parity with the general&#xD;
      population. Adipose tissue has broad effects on immune function relevant to HIV infection,&#xD;
      including the basal inflammatory state and peripheral lymphocyte populations, but there are&#xD;
      few data on the effects of high adiposity on HIV immunology. This issue is directly relevant&#xD;
      to promoting the long-term health of ART-treated individuals, many of which can now survive&#xD;
      for decades on treatment, as emerging evidence suggests that increased immune activation is a&#xD;
      major risk factor for the development of cardiovascular and metabolic diseases in this&#xD;
      population. HIV-infected individuals on ART have an approximately 2-fold higher risk of&#xD;
      myocardial infarction and a 4-fold higher risk of type 2 diabetes mellitus, and the&#xD;
      proportion of deaths among HIV-infected individuals due to non-AIDS conditions now exceeds&#xD;
      those due to AIDS.&#xD;
&#xD;
      Despite the increasing proportion of overweight and obese HIV-infected persons, few prior&#xD;
      studies have investigated the interaction between adipose tissue, immune activation, and risk&#xD;
      factors for cardiovascular and metabolic disease in treated HIV. The overall goal of this&#xD;
      study is to understand the complex relationships between adipose tissue, innate and cellular&#xD;
      immune activation, and metabolic and cardiovascular disease risk factors in persons on&#xD;
      long-term antiretroviral therapy. To this end, we will use an observational, cross-sectional&#xD;
      cohort design to compare in vivo markers of immune activation, ex vivo cytokine expression,&#xD;
      and metabolic and cardiovascular disease markers in HIV-infected individuals with a range of&#xD;
      body composition profiles and between overweight/obese HIV-infected and uninfected&#xD;
      individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HIV-infected individuals on long-term ART treatment are at increased risk for many diseases,&#xD;
      particularly diabetes mellitus and coronary artery disease, which are more commonly&#xD;
      associated with obesity and a sedentary lifestyle. As HIV patients are now living longer on&#xD;
      effective treatment, a growing proportion are becoming overweight and obese, and the&#xD;
      management of non-AIDS chronic diseases associated is emerging as a major challenge to&#xD;
      clinicians and the health care system. Excess adiposity (i.e., being overweight or obese) and&#xD;
      treated HIV infection are associated with strikingly similar alterations in inflammatory&#xD;
      biomarkers and cellular immune function implicated in the pathogenesis of chronic diseases,&#xD;
      but there are few data at present on whether the effects of obesity and treated HIV are&#xD;
      synergistic or additive. In this study we will closely investigate the effects of adipose&#xD;
      tissue on both the innate and cellular arms of the immune system, and the relationships&#xD;
      between adiposity, immune function, and risk factors for metabolic and cardiovascular&#xD;
      diseases.&#xD;
&#xD;
      Heightened, chronic systemic inflammation is an important contributor to non-AIDS related&#xD;
      morbidity and mortality among patients on ART, and treated HIV and obesity may promote&#xD;
      increased metabolic and cardiovascular disease through similar mechanisms. Elevated serum&#xD;
      highly-sensitive C-reactive protein (hsCRP; a more sensitive serum CRP assay used to measure&#xD;
      inflammation), interleukin-6 (IL-6), and other innate immune-derived inflammatory markers are&#xD;
      independently associated with increased risk of cardiovascular events, insulin resistance,&#xD;
      and all-cause death among HIV-infected individuals. The etiology of this HIV-associated&#xD;
      inflammation is not fully understood and likely multifactorial, but serum hsCRP and several&#xD;
      proinflammatory cytokines (e.g., IL-6, TNF-α receptor 1) correlate with fat mass in&#xD;
      HIV-infected adults, suggesting adipose tissue may have a role in modulating the inflammatory&#xD;
      response.&#xD;
&#xD;
      In addition to greater inflammation, abdominal obesity is associated with altered T cell&#xD;
      function, characterized by increased circulating markers of cellular immune activation (e.g.,&#xD;
      sCD25 and neopterin), and adipose tissue biopsies from obese individuals and animal models&#xD;
      contain higher numbers of resident macrophages, T cells (particularly CD8+ cells) and reduced&#xD;
      T-regulatory cells. Furthermore, adipokines (hormones produced by adipocytes), demonstrate a&#xD;
      range of lymphocyte effects. Leptin, in particular, enhances expression of T cell activation&#xD;
      markers after PHA stimulation, polarizes naïve CD4+ T cell proliferation towards the Th1&#xD;
      phenotype, and promotes Th1 cytokine production. These in vitro data are consistent with&#xD;
      obesity modulating T cell activation, at least in part through adipokine effects.&#xD;
&#xD;
      The goal of this study is to understand the complex relationships between adipose tissue,&#xD;
      innate and cellular immune activation, and metabolic and cardiovascular disease risk factors&#xD;
      in persons on long-term antiretroviral therapy. Using the facilities and resources of the&#xD;
      Vanderbilt Clinical Research Center, we will enroll an observational cohort to investigate&#xD;
      the interactions of innate immune activation, metabolic and cardiovascular risk factors, and&#xD;
      T cell activation among HIV-infected and uninfected adults with a range of body composition&#xD;
      profiles from low adiposity (lean) to high adiposity (obese). The study groups will be&#xD;
      comprised of 70 HIV-infected adults on ART with a range of body composition profiles from low&#xD;
      adiposity (lean) to high adiposity (obese), and a control group of 30 overweight and obese&#xD;
      uninfected individuals.&#xD;
&#xD;
      Hypothesis 1: Increased adipose tissue promotes increased innate and cellular immune&#xD;
      activation in HIV-infected individuals on long-term ART.&#xD;
&#xD;
      Specific Aim 1a: To study the hypothesis that adipose tissue promotes innate immune&#xD;
      activation in treated HIV by determining if serum leptin (a marker of adiposity) is&#xD;
      positively associated with interleukin-6 (IL-6) levels, in addition to other inflammation&#xD;
      biomarkers (including C-reactive protein), in HIV-infected persons on long-term ART with a&#xD;
      range of body composition profiles from low adiposity (lean) to high adiposity (obese).&#xD;
&#xD;
      Specific Aim 1b: To study the hypothesis that adipose tissue promotes cellular immune&#xD;
      activation in treated HIV by determining if serum leptin is positively associated with the&#xD;
      percentage of CD8+ T cells expressing CD38 and HLA-DR activation markers in HIV-infected&#xD;
      persons on long-term ART.&#xD;
&#xD;
      Hypothesis 2: Overweight and obese HIV-infected individuals on long-term ART have&#xD;
      significantly greater markers of innate and cellular immune activation compared to uninfected&#xD;
      individuals with equivalent adiposity.&#xD;
&#xD;
      Specific Aim 2a: To determine if IL-6 serum levels, and other inflammation biomarkers, are&#xD;
      significantly higher among overweight/obese HIV-infected persons compared to uninfected&#xD;
      controls with equivalent adiposity.&#xD;
&#xD;
      Specific Aim 2b: To determine if the percentage of CD38+ and HLA-DR+ CD8+ T cells is&#xD;
      significantly higher among overweight/obese HIV-infected persons compared to uninfected&#xD;
      controls with equivalent adiposity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 12, 2013</start_date>
  <completion_date type="Actual">February 15, 2020</completion_date>
  <primary_completion_date type="Actual">November 3, 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>CD38+ CD4+ T cells</measure>
    <time_frame>At study enrollment</time_frame>
    <description>Flow cytometry measurement of CD38 expression on isolated CD4+ T cells</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma interleukin-6</measure>
    <time_frame>At study enrollment</time_frame>
    <description>Level of circulating interleukin-6</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Carotid intima media thickness</measure>
    <time_frame>At study enrollment</time_frame>
    <description>Ultrasound measurement of carotid intima media thickness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brachial artery maximal flow mediated dilation</measure>
    <time_frame>At study enrollment</time_frame>
    <description>Ultrasound measurement of maximal brachial artery dilation after 5 minutes of hypoxia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visceral adipose tissue volume (cm3)</measure>
    <time_frame>At study enrollment</time_frame>
    <description>Dual-energy x-ray assessment of visceral adipose tissue volume</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Human Immunodeficiency Virus</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>HIV+ non-obese</arm_group_label>
    <description>HIV+ adults on antiretroviral therapy with a body mass index &lt;30 kg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV+ obese</arm_group_label>
    <description>HIV+ adults on antiretroviral therapy with a body mass index &gt;=30 kg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV-negative obese</arm_group_label>
    <description>HIV-negative adults on antiretroviral therapy with a body mass index &gt;=30 kg/m2</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>dual-energy X-ray absorptiometry (DEXA) scan</intervention_name>
    <description>Whole body dual-energy X-ray absorptiometry (DEXA) scan to assess lean and fat mass</description>
    <arm_group_label>HIV+ non-obese</arm_group_label>
    <arm_group_label>HIV+ obese</arm_group_label>
    <arm_group_label>HIV-negative obese</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Carotid and branchial artery ultrasound</intervention_name>
    <description>Ultrasound to assess carotid plaque and brachial artery flow mediated dilation</description>
    <arm_group_label>HIV+ non-obese</arm_group_label>
    <arm_group_label>HIV+ obese</arm_group_label>
    <arm_group_label>HIV-negative obese</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>2-hour oral glucose tolerace test</intervention_name>
    <description>Ingestion of 75g of glucose syrup with blood collection for glucose and insulin at time 0, 90min and 120min</description>
    <arm_group_label>HIV+ non-obese</arm_group_label>
    <arm_group_label>HIV+ obese</arm_group_label>
    <arm_group_label>HIV-negative obese</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood collection</intervention_name>
    <description>Blood collection for measurement of circulating proteins (cytokines) and isolation of immune cells</description>
    <arm_group_label>HIV+ non-obese</arm_group_label>
    <arm_group_label>HIV+ obese</arm_group_label>
    <arm_group_label>HIV-negative obese</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood mononuclear cells and plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Health persons with HIV receiving care at the Vanderbilt Comprehensive Care Clinic and&#xD;
        healthy persons without HIV receiving care at Vanderbilt University Medical Center&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        HIV-infected participants:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;18 years&#xD;
&#xD;
          -  on ART &gt;2 years&#xD;
&#xD;
          -  a CD4+ nadir &gt;100 cells/µl prior to starting ART&#xD;
&#xD;
          -  a CD4 &gt;350 cells/µl at the time of enrollment&#xD;
&#xD;
          -  HIV-1 viral load &lt;50 copies/ml&#xD;
&#xD;
          -  Pre-menopausal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant (women only)&#xD;
&#xD;
          -  Current use of anti-diabetic medications or statins&#xD;
&#xD;
        HIV uninfected participants:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;18 years&#xD;
&#xD;
          -  body mass index &gt;= 30 kg/m2&#xD;
&#xD;
          -  Pre-menopausal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant (women only)&#xD;
&#xD;
          -  Current use of anti-diabetic medications or statins&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Koethe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>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.</citation>
    <PMID>29794823</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27527002</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27175676</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>26418084</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>32064996</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>John R. Koethe</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan at this time to share IPD with other researchers. There have been no requests to share data.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04439448
org study id: K23AI100700
nct id: NCT04439448
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
HIV-infected individuals on long-term ART treatment are at increased risk for many diseases,
      particularly diabetes mellitus and coronary artery disease, which are more commonly
      associated with obesity and a sedentary lifestyle. As HIV patients are now living longer on
      effective treatment, a growing proportion are becoming overweight and obese, and the
      management of non-AIDS chronic diseases associated is emerging as a major challenge to
      clinicians and the health care system. Excess adiposity (i.e., being overweight or obese) and
      treated HIV infection are associated with strikingly similar alterations in inflammatory
      biomarkers and cellular immune function implicated in the pathogenesis of chronic diseases,
      but there are few data at present on whether the effects of obesity and treated HIV are
      synergistic or additive. In this study we will closely investigate the effects of adipose
      tissue on both the innate and cellular arms of the immune system, and the relationships
      between adiposity, immune function, and risk factors for metabolic and cardiovascular
      diseases.

      Heightened, chronic systemic inflammation is an important contributor to non-AIDS related
      morbidity and mortality among patients on ART, and treated HIV and obesity may promote
      increased metabolic and cardiovascular disease through similar mechanisms. Elevated serum
      highly-sensitive C-reactive protein (hsCRP; a more sensitive serum CRP assay used to measure
      inflammation), interleukin-6 (IL-6), and other innate immune-derived inflammatory markers are
      independently associated with increased risk of cardiovascular events, insulin resistance,
      and all-cause death among HIV-infected individuals. The etiology of this HIV-associated
      inflammation is not fully understood and likely multifactorial, but serum hsCRP and several
      proinflammatory cytokines (e.g., IL-6, TNF-α receptor 1) correlate with fat mass in
      HIV-infected adults, suggesting adipose tissue may have a role in modulating the inflammatory
      response.

      In addition to greater inflammation, abdominal obesity is associated with altered T cell
      function, characterized by increased circulating markers of cellular immune activation (e.g.,
      sCD25 and neopterin), and adipose tissue biopsies from obese individuals and animal models
      contain higher numbers of resident macrophages, T cells (particularly CD8+ cells) and reduced
      T-regulatory cells. Furthermore, adipokines (hormones produced by adipocytes), demonstrate a
      range of lymphocyte effects. Leptin, in particular, enhances expression of T cell activation
      markers after PHA stimulation, polarizes naïve CD4+ T cell proliferation towards the Th1
      phenotype, and promotes Th1 cytokine production. These in vitro data are consistent with
      obesity modulating T cell activation, at least in part through adipokine effects.

      The 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. Using the facilities and resources of the
      Vanderbilt Clinical Research Center, we will enroll an observational cohort to investigate
      the interactions of innate immune activation, metabolic and cardiovascular risk factors, and
      T cell activation among HIV-infected and uninfected adults with a range of body composition
      profiles from low adiposity (lean) to high adiposity (obese). The study groups will be
      comprised of 70 HIV-infected adults on ART with a range of body composition profiles from low
      adiposity (lean) to high adiposity (obese), and a control group of 30 overweight and obese
      uninfected individuals.

      Hypothesis 1: Increased adipose tissue promotes increased innate and cellular immune
      activation in HIV-infected individuals on long-term ART.

      Specific Aim 1a: To study the hypothesis that adipose tissue promotes innate immune
      activation in treated HIV by determining if serum leptin (a marker of adiposity) is
      positively associated with interleukin-6 (IL-6) levels, in addition to other inflammation
      biomarkers (including C-reactive protein), in HIV-infected persons on long-term ART with a
      range of body composition profiles from low adiposity (lean) to high adiposity (obese).

      Specific Aim 1b: To study the hypothesis that adipose tissue promotes cellular immune
      activation in treated HIV by determining if serum leptin is positively associated with the
      percentage of CD8+ T cells expressing CD38 and HLA-DR activation markers in HIV-infected
      persons on long-term ART.

      Hypothesis 2: Overweight and obese HIV-infected individuals on long-term ART have
      significantly greater markers of innate and cellular immune activation compared to uninfected
      individuals with equivalent adiposity.

      Specific Aim 2a: To determine if IL-6 serum levels, and other inflammation biomarkers, are
      significantly higher among overweight/obese HIV-infected persons compared to uninfected
      controls with equivalent adiposity.

      Specific Aim 2b: To determine if the percentage of CD38+ and HLA-DR+ CD8+ T cells is
      significantly higher among overweight/obese HIV-infected persons compared to uninfected
      controls with equivalent adiposity.
observational model: Cohort
time perspective: Cross-Sectional
measure: CD38+ CD4+ T cells
time frame: At study enrollment
description: Flow cytometry measurement of CD38 expression on isolated CD4+ T cells
measure: Plasma interleukin-6
time frame: At study enrollment
description: Level of circulating interleukin-6
measure: Carotid intima media thickness
time frame: At study enrollment
description: Ultrasound measurement of carotid intima media thickness
measure: Brachial artery maximal flow mediated dilation
time frame: At study enrollment
description: Ultrasound measurement of maximal brachial artery dilation after 5 minutes of hypoxia
measure: Visceral adipose tissue volume (cm3)
time frame: At study enrollment
description: Dual-energy x-ray assessment of visceral adipose tissue volume
arm group label: HIV+ non-obese
description: HIV+ adults on antiretroviral therapy with a body mass index <30 kg/m2
arm group label: HIV+ obese
description: HIV+ adults on antiretroviral therapy with a body mass index >=30 kg/m2
arm group label: HIV-negative obese
description: HIV-negative adults on antiretroviral therapy with a body mass index >=30 kg/m2
intervention type: Radiation
intervention name: dual-energy X-ray absorptiometry (DEXA) scan
description: Whole body dual-energy X-ray absorptiometry (DEXA) scan to assess lean and fat mass
arm group label: HIV+ non-obese
arm group label: HIV+ obese
arm group label: HIV-negative obese
intervention type: Other
intervention name: Carotid and branchial artery ultrasound
description: Ultrasound to assess carotid plaque and brachial artery flow mediated dilation
arm group label: HIV+ non-obese
arm group label: HIV+ obese
arm group label: HIV-negative obese
intervention type: Diagnostic Test
intervention name: 2-hour oral glucose tolerace test
description: Ingestion of 75g of glucose syrup with blood collection for glucose and insulin at time 0, 90min and 120min
arm group label: HIV+ non-obese
arm group label: HIV+ obese
arm group label: HIV-negative obese
intervention type: Diagnostic Test
intervention name: Blood collection
description: Blood collection for measurement of circulating proteins (cytokines) and isolation of immune cells
arm group label: HIV+ non-obese
arm group label: HIV+ obese
arm group label: HIV-negative obese
Peripheral blood mononuclear cells and plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John Koethe, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: John R. Koethe
investigator title: Associate Professor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
sharing ipd: No
ipd description: There is no plan at this time to share IPD with other researchers. There have been no requests to share data.