Use of EndoPAT for Measurements of Endothelial Dysfunction in HIV Infected Children and Healthy Controls
Condition: HIV; Endothelial Dysfunction
Study type: Observational

Summary: 
      Our objective is to determine whether HIV infected youth have higher level of endothelial
      dysfunction, as measured by Peripheral Arterial Tonometry, when compared to age matched
      healthy controls. The investigators also aim to gather preliminary data on whether
      endothelial Peripheral Arterial Tonometry (endoPAT) measurements of endothelial dysfunction
      are independently associated with HIV and antiretroviral factors, and with markers of
      inflammation and traditional cardiovascular disease risk.
    

Detailed description: 
      Study Objectives and Hypothesis Our objective is to determine whether HIV infected youth have
      higher level of endothelial dysfunction, as measured by Peripheral Arterial Tonometry, when
      compared to age matched healthy controls. We also aim to gather preliminary data on whether
      endoPAT measurements of endothelial dysfunction are independently associated with HIV and
      antiretroviral factors, and with markers of inflammation and traditional cardiovascular
      disease risk.

      Specific Aim 1:

      To compare endothelial function, as measured by endoPAT, between HIV-infected youth and
      matched healthy controls.

      Hypothesis: HIV infected youths will have impaired endothelial function compared to age
      matched healthy controls.

      Specific Aim 2:

      To determine risk factors of endothelial dysfunction by evaluating: 1) risk factors specific
      to HIV such as disease stage, cluster of differentiation 4 (CD4) count, HIV viral load,
      specific ART regimen, perinatally acquired versus behaviorally acquired infection; 2) markers
      of cardiovascular disease risk such as smoking, lipid levels, insulin resistance; 3) markers
      of inflammation and immune activation Hypothesis: Endothelial dysfunction will correlate with
      advanced HIV disease stage, use of protease inhibitors and worse traditional cardiovascular
      disease risk factors including lipids, insulin resistance, and smoking.

      Specific Aim 3:

      To assess whether endothelial function changes over a period of 24 weeks in HIV infected
      youths and controls.

      Hypothesis: Endothelial dysfunction will progress over time in HIV-infected children but not
      in healthy controls.

      Study Design This is a 24-week observational cohort study to gather preliminary data on the
      prevalence and risk factors for endothelial dysfunction in HIV-infected youths. Children
      enrolled will be between the ages of 8 and 30 years and either congenitally or behaviorally
      infected with HIV, on continuous ART for at least 6 months and with HIV-1 RNA <1,000
      copies/mL. We will also enroll an age- and gender-matched group of healthy controls. A total
      of 50 HIV-infected children/young adults and 50 matched controls will be enrolled.

      Evaluations will be performed at two time points: baseline and week 24. At both visits,
      evaluations will be similar. We will collect demographic data and medical history including
      date of birth, sex, gender, CD4 cell count nadir, past and current ART and non-ART medication
      history, HIV stage based on the CDC guidelines, HIV diagnosis date and method of HIV
      acquisition, alcohol, smoking and drug habits, as well as family history of cardiovascular
      disease or diabetes. We will record clinical measurements including blood pressure, physical
      examination abnormalities, waist and hip circumferences and tanner stage. Subjects will
      undergo laboratory measurements of lipids levels and markers of insulin resistance in a
      fasting state (>8 hrs fast except for water and medications), as well as inflammation and
      immune activation markers (hsCRP, Interleukin 6 or IL-6, sCD14). HIV RNA and CD4 cell count
      will be collected from clinical records. Plasma and serum will be stored for possible future
      measurements of other inflammation and cardiovascular markers. We will perform endothelial
      function measurements by PAT as recommended by the manufacturer.

      Controls will be recruited from the community using Institutional Review Board (IRB)-approved
      flyers, as uninfected siblings or relatives of the HIV-infected patients, or from physician
      referrals.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        1. HIv positive: subjects seen at the Special Immunology Unit

          2. Controls: HIV-negative controls will be healthy people who are friends or family
             members of the HIV-infected patients, or employees who are not employed by the
             principal investigator or the co-investigators or recruited through researchmatch.org
      
Biospecimen description: 
      plasma and serum