Pilot Award Recipient: Georges Haddad, PhD

Effects of cART on the Heart

George Haddad
January 10, 2022
The pandemic of the Acquired Immunodeficiency Syndrome due to the lentiviral retrovirus, Human Immunodeficiency Virus Type 1 (HIV-1) is still affecting millions of people with more than 70 million infected individuals worldwide and more than 40 million deaths already. In the USA, there are about 1.2 million people above the age of 13 living with HIV and about 12,000 individuals diagnosed with perinatally acquired HIV-infection. In 2019, there were 36,801 newly diagnosed cases with over 70% of those cases within the African American and Hispanic communities adding to the significant health disparities within these communities. The advent of combination antiviral therapy (cART) has significantly reduced the spread of HIV-1 and related deaths in the last decade. The typical cART regimen consists of two Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI) alongside an Integrase Strand Transfer Inhibitor (INSTI) or a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI). Although cART is essential for people living with HIV to maintain undetectable viral loads, potential long-term effects on organ systems remain unknown. In fact, there is an evolving concern about cART patients presenting an increased rate of cardiovascular (CV) diseases with prolonged usage that can affect quality of life and life expectancy, independently from ageing. Furthermore, non-infected newborns from cART-treated HIV-infected pregnant mothers, have shown higher risk for cardiac dysfunction and dysmorphisms (e.g., ventricular wall thinning and septal defects). Despite the significance of the potential negative cardiovascular impact of cART, there is a scarcity of research and a gap in our knowledge deciphering the direct mechanism(s) of such therapy on the cardiomyocytes. The overall objective of this pilot application is to initiate an-in depth innovative assessment of the effects of cART on the survival and function of cardiomyocytes using molecular and cellular imaging techniques. Our central hypothesis is that cART-treated cardiomyocytes will exhibit increased apoptosis and reduced survivability with weakened contractility and calcium response. We also hypothesize that these negative cardiac effects would be more prominent in adult than the neonatal cardiomyocytes. These studies will establish a platform to investigate the (1) long-term assessment of different cART regimens on the cardiovascular system as new ARTs are being developed (2) in depth analysis of signaling mechanisms involved in cART induced