New R01 Awarded to DC CFAR Developmental Core Director and Basic Sciences Core Co-Director, Michael Bukrinsky, MD, PhD

Dr. Michael Bukrinsky Photo
August 30, 2018
DC CFAR investigator, Michael Bukrinksky, MD, PhD, has recently been awarded an R01 from the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) entitled, "Epigenetic Reprogramming in HIV-Associated Cardio-Vascular Disease".
This project will study the increased risk for atherosclerosis and cardiovascular disease (CVD) associated with HIV infection - a risk that does not diminish once the HIV viral load is suppressed to undetectable levels through the use of combined anti-retroviral therapy (cART). This persistence of risk may be driven in part by the metabolic effects of cART; however, the researchers posit that this cannot be the main reason as the new generation of cART have reduced metabolic side effects. They hypothesize that the excess risk may be caused by a two-part mechanism: HIV replication during the early, untreated phase of infection induces innate memory in myeloid cells increasing their responsiveness to TLR ligands, which persists after cART initiation, so that even low levels of bacterial translocation through the incompletely recovered gut mucosa lead to persistent inflammation and CVD. This hypothesis is based on published literature showing trained innate immunity after exposure of monocytes to fungal cell wall β-glucans, and on the researcher's preliminary evidence that HIV Nef drives trained immunity of human monocytes. This project, using cells from HIV+ patients and mouse models, explores how HIV may reprogram macrophages to a more activated inflamed state which could continue to cause atherosclerosis even after infection is controlled.
Click here to read the full abstract.