Innate immune system activation is a recognized feature of chronic HIV infection that may contribute to HIV disease progression as well increasingly important non-classic HIV complications such as cardiovascular disease (CVD). This proposal will a) identify mechanisms linking innate immunity with CVD in the setting of chronic, treated HIV infection;b) develop novel serum biomarkers for monocyte/macrophage related inflammation and coagulation that may stratify CVD risk in the HIV-infected population;c) use global sequencing of RNAs (RNA-Seq) to define HIV- and CVD-associated gain and/or loss of function of specific signaling pathways by studying CD14++ and CD14+CD16+ monocyte subsets from well-characterized HIV+ and HIV- patient groups. Extensively characterized HIV infected and HIV uninfected enrollees from the WIHS and MACS NIH cohorts are brought to bear in this interdisciplinary, multi-site investigation. This project will thereby provide insight into the observed links of HIV infection and related comorbidities (e.g., HCV coinfection) with CVD risk, identifying the innate immune system as a novel and modifiable explanatory pathway. This is of high clinical relevance given the need for improved CVD risk stratification, as well as the feasibility of intervening on mechanisms mediated by monocyte/macrophage activity. ?

Public Health Relevance

Public Health Relevance Statement This research project is of high clinical relevance given the need for improved CVD risk stratification, as well as the feasibility of intervening on mechanisms mediated by monocyte/macrophage activity. This project will elucidate the innate immune system as a novel independent pathway linking HIV and CVD. It will refine a serum biomarker panel for prospective CVD risk which has potential clinical application. We also uncover the mechanisms for the already-established link between macrophage/monocyte biomarkers and CVD using both candidate and discovery approaches. The results have high clinical relevance leading to: 1) development of strategies to intervene on innate immune system pathways (PPAR, statins, mTOR);2) vetting a new research biomarker of innate immunity;and 3) better risk prediction and thus accurate targeting of CVD prevention, overcoming inaccuracy of existing CVD risk scores in HIV+ patients. ?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Fleg, Jerome
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Albert Einstein College of Medicine
Public Health & Prev Medicine
Schools of Medicine
United States
Zip Code
Moran, Caitlin A; Sheth, Anandi N; Mehta, C Christina et al. (2018) The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women. AIDS 32:999-1006
Glesby, Marshall J; Hanna, David B; Hoover, Donald R et al. (2018) Abdominal Fat Depots and Subclinical Carotid Artery Atherosclerosis in Women With and Without HIV Infection. J Acquir Immune Defic Syndr 77:308-316
Kobiyama, Kouji; Ley, Klaus (2018) Atherosclerosis. Circ Res 123:1118-1120
Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei et al. (2018) Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study. J Lipid Res 59:1967-1976
Hanna, David B; Moon, Jee-Young; Haberlen, Sabina A et al. (2018) Carotid artery atherosclerosis is associated with mortality in HIV-positive women and men. AIDS 32:2393-2403
Huck, Daniel M; Hanna, David B; Rubin, Leah H et al. (2018) Carotid Artery Stiffness and Cognitive Decline Among Women With or at Risk for HIV Infection. J Acquir Immune Defic Syndr 78:338-347
Kimura, Takayuki; Kobiyama, Kouji; Winkels, Holger et al. (2018) Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B. Circulation 138:1130-1143
Hanna, David B; Lin, Juan; Post, Wendy S et al. (2017) Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men. J Infect Dis 215:1352-1361
Ley, Klaus; Gerdes, Norbert; Winkels, Holger (2017) ATVB Distinguished Scientist Award: How Costimulatory and Coinhibitory Pathways Shape Atherosclerosis. Arterioscler Thromb Vasc Biol 37:764-777
Butterfield, Tiffany R; Hanna, David B; Kaplan, Robert C et al. (2017) Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease. AIDS 31:199-205

Showing the most recent 10 out of 24 publications