Inflammation, Viral Replication, and Atherosclerosis in Treated HIV Infection
Condition: Atherosclerosis
MeSH terms: HIV Infections; Atherosclerosis
Study type: Observational

Summary: 
      This is a longitudinal observational study of HIV-infected patients and HIV-negative control
      patients that is being conducted to learn more about immunologic factors, inflammation, and
      cardiovascular risk in patients with HIV infection or in patients with autoimmune disease.
      The investigators plan to obtain measurement of carotid artery intima media thickness (IMT)
      using high resolution ultrasound as a noninvasive means for tracking atherosclerotic
      progression. The investigators will also measure lipid and lipoprotein levels, inflammatory
      markers, markers of Cytomegalovirus (CMV) infection, thrombotic markers, atherogenic
      lipoproteins, and markers of immune function. Immunophenotyping will be performed on freshly
      collected blood and analyzed by flow cytometry to identify activated T-cells, T-cell
      turnover, proportions of T-cells, and CMV function. HIV-infected patients will have CD4 count
      and HIV viral load measured in addition. Patients will undergo detailed clinical history
      including HIV disease, specific HIV medications, comorbid conditions, and health related
      behaviors. Physical exam and measurements will be obtained to assess for the presence of
      lipodystrophy. Patients will undergo study visits for ultrasound, blood draw, and interview
      at 4-12 month intervals for the next 3 years.

      Patients will also go assessment of endothelial function, endothelial progenitor cells,
      arterial stiffness as measured using pulse wave tonometry.

      To demonstrate the feasibility of a larger scale investigation of cardiac arrhythmia in HIV
      positive and negative patients with cardiac disease, the investigators will use 48-hour
      Holter monitor surveillance to monitor HIV-infected and uninfected patients with a history of
      myocardial infarction, systolic left ventricular dysfunction, and/or pulmonary artery
      hypertension for the presence of cardiac arrhythmia.

      The FDG PET scan (18F-fluorodeoxyglucose positron emission tomography-computed tomography)
      will be used to detect and quantify inflammation in the body.
    

Detailed description: 
      This proposal is currently approved by CHR (#H9577-18534-03C, exp date 3/26/04); the purpose
      of this new application is to split the currently approved protocol into a separate protocol
      with a separate PI. Data collected and patients seen under the previously approved protocol
      will be carried over into this new separate protocol. This is a longitudinal observational
      study of HIV-infected patients and HIV-negative control patients, and individuals with
      autoimmune diseases. We plan to obtain measurement of carotid artery intima media thickness
      (IMT) using high resolution ultrasound as a noninvasive means for tracking atherosclerotic
      progression. In addition, patients will undergo ct scan for coronary calcium and single slice
      abdominal ct scan to assess visceral fat. We will also measure lipid and lipoprotein levels,
      inflammatory markers, markers of CMV infection, thrombotic markers, atherogenic lipoproteins,
      and markers of immune function. Immunophenotyping will be performed on freshly collected
      blood and analyzed by flow cytometry to identify activated T cells,T cell turnover,
      proportions of T cells, and CMV function. HIV-infected patients will have CD4 count and HIV
      viral load measured in addition. Patients will undergo detailed clinical history including
      HIV disease, specific HIV medications, comorbid conditions, and health related behaviours.
      Physical exam and measurements will be obtained to assess for the presence of lipodystrophy.
      Patients will undergo study visits for ultrasound, blood draw, and interview at 4-12 month
      intervals for the next 3 years. Patients will also go assessment of endothelial function,
      endothelial progenitor cells, arterial stiffness as measured using pulse wave tonometry. In
      patients with detectable calcium on CT scan, they will be given the option of obtaining CT
      angiography. Patients will also undergo testing for peripheral arterial disease using ankle
      brachial index testing and exercise treadmill testing.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        325 well-characterized HIV-infected individuals and 75 HIV-uninfected individuals.
      
Keywords: Human Immunodeficiency Virus; Atherosclerosis; Inflammation; Endothelial Function; Thrombosis