Protocol Number: 09-I-0013

Title:

Biomarkers of Inflammation, Coagulation, and Endothelial Function in HIV-Infected Adults

Number:

09-I-0013

Summary:

D-dimer, a fibrin degradation product generated as a result of plasmin mediated clot dissolution processes, is an indicator of recent clot formation and subsequent fibrinolysis. Analysis of D-dimer concentration is employed in the diagnosis of deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. More recently, D-dimer levels have been correlated with atherosclerotic cardiovascular disease. In a recent case-control study of biomarkers for cardiovascular disease in human immunodeficiency virus (HIV)-infected adults, baseline D-dimer levels strongly correlated with all-cause mortality. Notably, the association between baseline D-dimer levels and death due to cardiovascular disease was less significant.

At present, the pathophysiology underlying the association of elevated D-dimer concentrations with mortality in HIV is not understood. This study seeks to identify possible mechanisms underlying D-dimer elevations in HIV-infected adults by investigating a number of pathways that may be associated with the elevations using biomarkers of inflammation, hemostasis, thrombosis, platelet function, lipid metabolism, and additional indicators of endothelial function. Further elucidation of plausible pathways contributing to D-dimer elevation could, ultimately, lead to trials of risk-reducing interventions for patients with an elevated D-dimer level.

This study, an exploratory, cross-sectional study of up to 200 subjects, seeks to prospectively collect data on D-dimer and related biomarkers in HIV-infected adults. Initially, the study will recruit HIV-infected adults with HIV viremia who are not taking antiretroviral therapy and compare their clinical histories and biomarker findings with those from (1) a group of HIV-infected adults with controlled HIV viremia who are receiving antiretroviral therapy, and with those from (2) a control group of HIV-negative healthy subjects.

The study requires 2 visits for screening, history and physical examination, and phlebotomy. A wide array of research assays investigating different aspects of inflammation, coagulation, and endothelial function will be completed. Samples will be stored for future investigation.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

- Age greater than or equal to 18 years

- Ability to understand and provide informed consent

- Adequate venous access

- Adequate blood counts (hemoglobin greater than or equal to 9.0 g/dL, platelets greater than or equal to 50,000 cells/mm(3))

- Willing and able to comply with study requirements and procedures including storage of blood samples for use in future studies of HIV, AIDS, immune function, inflammation, coagulation, and atherosclerosis

- Negative serum pregnancy test for females of child-bearing potential (female subjects who have medical documentation of hysterectomy and/or bilateral oophorectomy do not need to undergo pregnancy testing)

For HIV-negative subjects:

- No known history of HIV infection. At enrollment, HIV antibody testing will be performed to confirm negative HIV-1 antibody status.

For HIV-positive subjects:

- Established HIV diagnosis (previous documentation of HIV-1 infection in the subject's medical record; for subjects without such confirmation, positive ELISA testing confirmed by Western Blot or plasma HIV viral load greater than 10,000 copies/mL)

- Must be under the care of a physician for HIV and general medical issues.

EXCLUSION CRITERIA:

-Pregnant or breast-feeding

-Known bleeding or clotting disorder including history of deep vein thrombosis, pulmonary embolism, or hemophilia

-Current use of warfarin, low molecular weight heparin, clopidogrel or experimental platelet aggregation inhibitor

-Concurrent malignancy requiring cytotoxic chemotherapy or radiation therapy

-Substance abuse or severe psychiatric disorder that would interfere with adherence to protocol requirements

-Any serious medical condition for which the principal investigator feels participation may be contraindicated

Special Instructions:

Currently Not Provided

Keywords:

Cardiovascular Disease

D-dimer

Antiretroviral

Mortality

Recruitment Keyword(s):

HIV Positive

HIV Negative

Healthy Volunteer

HV

Condition(s):

HIV

Antiretroviral

Hypercoaguable State

Cardiovascular Disease

Healthy Volunteer

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol. 2003 Sep 17;42(6):1037-43.

Fathi R, Haluska B, Isbel N, Short L, Marwick TH. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol. 2004 Feb 18;43(4):616-23.

Shimbo D, Grahame-Clarke C, Miyake Y, Rodriguez C, Sciacca R, Di Tullio M, Boden-Albala B, Sacco R, Homma S. The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis. 2007 May;192(1):197-203

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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