131. Clonal Hematopoiesis is associated with risk of Cardiovascular Disease in individuals with Human Immunodeficiency Virus

Aly Abdelkareem

Brian Wiley


Brian Wileya, Tyler Parsona, Kelly Boltona, Grant Challena, Andrew Younga, Rachel Prestia, Sammi Burkarta, Kristin Erlandsonb, Katherine Tassiopoulosc

aWashington University, St. Louis, MO, USA; bUniversity of Colorado, Anschutz Medical Campus, Aurora, CO, USA; cHarvard T.H. Chan School of Public Health, Boston, MA, USA

An estimated 1.2 million individuals in the USA are living with HIV (www.hiv.gov). Thanks to modern antiretroviral therapies (ART), the life expectancies of individuals living with HIV now approach those of people without HIV (Marcus 2020). But with this, an increase in the proportion of deaths due to non-infectious causes has occurred including, predominately, cardiovascular disease (CVD). Multiple studies have shown that HIV infection is an independent risk factor for cardiovascular disease. This increased risk is multifactorial due to an increased prevalence of traditional CVD risk factors and HIV-specific risk factors including ART, chronic inflammation and immune activation (Hsue 2010). Clonal Hematopoiesis, characterized by the expansion of blood cells stemming from a mutant hematopoietic stem/progenitor cell (HSPCs) is an emerging risk factor for cardiovascular disease. Mechanistically, this is thought to be driven, at least in part, by CH-induced proinflammatory circulating leukocytes (Jaiswal 2017, Bick 2020). Recent data suggest that inflammatory states may also promote the expansion of DNMT3A and TET2 CH mutant HSPCs suggesting a potential feedback loop (Zheng 2019, King 2019). CH has been recently reported to be increased among individuals living with HIV (Dharan 2021). To our knowledge, little is known whether CH is a risk factor for HIV-associated CVD. Given evidence of an increased prevalence of CH among those with HIV, we hypothesized that CH would predict risk of CVD.

Among individuals with HIV, we discovered CH is associated with a nearly four-fold increased risk of CVD.