HIV and Cardiovascular Risk

Assessment of Cardiovascular Risk in HIV Patients

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Cardiovascular Disease

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 129

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Flyers and advertisements regarding this study will be posted in community centers and newspapers

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; HIV Positive men and women 18-65 years of age
2; HIV negative men and women 18-65 years of age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood pressure	2 years
Carotid Intima Media Thickness	2 years
Waist Circumference	2 years
Lipid levels	2 years
Glucose	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Inflammatory markers	2 years
Visceral adiposity	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Steven K Grinspoon, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Fitch KV, Stavrou E, Looby SE, Hemphill L, Jaff MR, Grinspoon SK. Associations of cardiovascular risk factors with two surrogate markers of subclinical atherosclerosis: endothelial function and carotid intima media thickness. Atherosclerosis. 2011 Aug;217(2):437-40. doi: 10.1016/j.atherosclerosis.2011.04.009. Epub 2011 Apr 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: April 24, 2007
• First Submitted That Met QC Criteria: April 24, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 30, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Treatment Experienced; HIV Infection; Antiretroviral Therapy; Inflammatory Markers
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Cardiovascular Diseases
• Other Study ID Numbers: DK49302-10AR; R01DK049302 (U.S. NIH Grant/Contract)