This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). Subjects will include 750 HIV-infected and 250 HIV-uninfected women participating in the Follow-up Phase of the WIHS Carotid Artery Ultrasound Study. The set of specific aims include two primary aims:
Aim 1 focuses on established inflammation and coagulation biomarkers as predictors of subclinical atherosclerosis.
Aim 2 examines lipid changes which constitute "classic" vascular risk factors. Data analysis goals are: (1) To correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status;(2) To determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women;(3) To determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. In addition, we propose three exploratory aims examining novel immune and inflammatory mediators that may be of importance to atherosclerosis in HIV-infected adults: 1. Translocation of gut microbes, as measured by 16s RNA;2. T-cell senescence (CD4+CD28- and CD8+CD28- T-cells);3. T regulatory cells. This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). We will (1) correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status;(2) determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women;and (3) determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis.

Public Health Relevance

This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). We will (1) correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status;(2) determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women;and (3) determine changes in classic vascular risk factors (eg, lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. 3/25/2008 1 C: Documents and Settings calabres Local Settings Temporary Internet Files OLK1EA Narrative 25Mar08.doc Created on 3/25/2008 9:34:00 AM

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095140-05
Application #
8320220
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Program Officer
Mcdonald, Cheryl
Project Start
2008-09-25
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$423,448
Indirect Cost
$126,127
Name
Albert Einstein College of Medicine
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Shendre, Aditi; Irvin, Marguerite R; Aouizerat, Bradley E et al. (2014) RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women's Interagency HIV Study (WIHS). Atherosclerosis 233:666-72
Shaked, Iftach; Hanna, David B; Glei├čner, Christian et al. (2014) Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection. Arterioscler Thromb Vasc Biol 34:1085-92
Kuniholm, Mark H; Xie, Xianhong; Anastos, Kathryn et al. (2014) Association of chronic hepatitis C infection with T-cell phenotypes in HIV-negative and HIV-positive women. J Acquir Immune Defic Syndr 67:295-303
Kuniholm, Mark H; Parrinello, Christina M; Anastos, Kathryn et al. (2013) Hepatitis C viremia is associated with cytomegalovirus IgG antibody levels in HIV-infected women. PLoS One 8:e61973
Parrinello, Christina M; Landay, Alan L; Hodis, Howard N et al. (2013) Treatment-related changes in serum lipids and inflammation: clinical relevance remains unclear. Analyses from the Women's Interagency HIV study. AIDS 27:1516-9
Karim, Roksana; Mack, Wendy J; Kono, Naoko et al. (2013) Gonadotropin and sex steroid levels in HIV-infected premenopausal women and their association with subclinical atherosclerosis in HIV-infected and -uninfected women in the women's interagency HIV study (WIHS). J Clin Endocrinol Metab 98:E610-8
Parrinello, Christina M; Sinclair, Elizabeth; Landay, Alan L et al. (2012) Cytomegalovirus immunoglobulin G antibody is associated with subclinical carotid artery disease among HIV-infected women. J Infect Dis 205:1788-96
Kaplan, Robert C; Sinclair, Elizabeth; Landay, Alan L et al. (2011) T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis 203:452-63
Kaplan, Robert C; Sinclair, Elizabeth; Landay, Alan L et al. (2011) T cell activation predicts carotid artery stiffness among HIV-infected women. Atherosclerosis 217:207-13
Seaberg, Eric C; Benning, Lorie; Sharrett, A Richey et al. (2010) Association between human immunodeficiency virus infection and stiffness of the common carotid artery. Stroke 41:2163-70

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