HIV and Cardiovascular Risk
HIV and Cardiovascular Risk
HIV-infected patients treated with combination antiretroviral therapy demonstrate metabolic
 abnormalities that may predispose them to cardiovascular disease. In HIV-infected patients we
 will investigate progression rates of cardiovascular disease and assess whether these
 progression rates are predicted by increased inflammatory indices.
HIV-infected patients treated with combination antiretroviral (ARV) therapy increasingly
 demonstrate metabolic abnormalities, including dyslipidemia, insulin resistance and body
 composition abnormalities that may predispose them to cardiovascular disease (CVD). Initial
 studies suggest increased carotid intima-media thickness (IMT) and endothelial dysfunction in
 this population. Increased carotid IMT over time has been demonstrated in HIV-infected
 patients compared to control subjects. However, traditional risk factors, such as
 dyslipidemia, diabetes mellitus and body composition changes alone do not fully predict
 increased cardiovascular disease in HIV-infected patients. One possible explanation is
 increased inflammation, related directly to effects of ARV therapy or indirectly from changes
 in fat distribution. In preliminary studies, our group has shown that changes in fat
 distribution were highly predictive of TNF and IL-6, as well as adiponectin, and that
 specific inflammatory cytokines were related in cross-sectional studies to increased IMT. In
 the proposed study we will investigate using detailed methodologies the relationship between
 adipocytokine concentrations and subclinical atherosclerosis in both cross-sectional and
 longitudinal studies. We will determine in HIV-infected patients on ARVs for greater than 6
 months, progression rates of IMT and whether progression rates are predicted by increased
 inflammatory indices, controlling for traditional risk factors, and body composition changes.
 We will test the hypothesis that inflammation, more than traditional risk factors and ARV
 use, mediates subclinical atherosclerotic disease in HIV-infected patients.
Inclusion Criteria:

 Inclusion Criteria for Group 1 (HIV-infected group)

 1. Age greater than or equal to 18 and less than or equal to 65 years of age

 2. HIV positive, on the same combination ARV regimen for > than 6 months, including but
 not limited to either 2 NRTIs and an NNRTI or PI, or a triple NRTI regimen

 3. CD4 >350 cells/mm3

 Inclusion Criteria for Group 2 (HIV Negative, Healthy Control, age and BMI matched to HIV
 subjects)

 1. No history of HIV infection (negative HIV test)

 2. Age greater than or equal to 18 and less than or equal to 65 years of age

 Exclusion Criteria:

 Exclusion Criteria for Group 1 (HIV-infected group)

 1. Hgb < 10.0 g/dL, creatinine > 1.5 mg/dL, SGPT > 2.5x ULN

 2. Use of glucocorticoid, testosterone, growth hormone or other anabolic agents within
 the past 6 months

 3. New antiretroviral regimen within 6 months of study initiation

 4. Active substance abuse

 5. Medications known to affect glucose or body composition

 6. Positive pregnancy test or recently pregnant within the past year or lactating

 7. Presence of active cancers

 8. Acute viral, bacterial or other infections (excluding HIV)

 9. Weight loss in the past 3 months of greater than 10 pounds

 Criteria for Group 2 (HIV Negative, Healthy Control, age and BMI matched to HIV subjects)

 1. Hgb < 10.0 g/dL, creatinine > 1.5 mg/dL, SGPT > 2.5x ULN

 2. Use of glucocorticoid, testosterone, growth hormone or other anabolic agents within
 the past 6 months.

 3. Active substance abuse

 4. Medications known to affect glucose or body composition

 5. Positive pregnancy test or recently pregnant within the past year or lactating

 6. Acute viral, bacterial or other infections

 7. Weight loss in the past 3 months of greater than 10 pounds