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.

Eligibility Criteria:
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