STUDIES TO EVALUATE THE CARDIOVASCULAR TOXICITY OF AN HIV TRICOMBO THERAPY (ABC/DTG/3TC) IN SPRAGUE DAWLEY (HSD: SPRAGUE DAWLEY® SD®) RATS (F0 DOSED BY ORAL GAVAGE

NIH RePORTER · NIH · N01 · $2,456,000 · view on reporter.nih.gov ↗

Abstract

HIV infections remain prevalent with almost 38 million people affected worldwide. In the US alone the current HIV positive population is estimated to be between 1 and 3.5 million individuals, with about 30,000 new cases being diagnosed every year (UNAIDS/WHO and hiv.gov). In the past 30 years antiretroviral therapies (ART) have aided in the management of the acquired immune deficiency syndrome (AIDS) resulting from HIV, changing the disease from a fatal infection in the early 90s to a chronically managed condition in the mid-2000s. ARTs are most often administered in a cocktail which contain 2-3 drugs (cART). The phenotype of cardiomyopathy in the HIV-positive population has changed after the implementation of cART. Initially, it was characterized by myocarditis associated with opportunistic viral infections in immunocompromised patients. It is now defined as asymptomatic systolic or diastolic dysfunction that is detected by echocardiography. While the state of chronic low-grade inflammation associated with the remaining presence of the virus despite ART is likely involved in this increased risk, the extent to which cART itself contributes to these effects is unknown. Data on the effects of cART on HIV-negative individuals is scarce and animal models involving HIV therapeutics have largely focused on humanized models in which the virus is present. The overarching hypothesis underlying this project is that exposure to cART induces cardiometabolic remodeling that increases the risk for latent cardiovascular disease. Also, it is hypothesized that such remodeling is more prevalent when exposure occurs in the developing embryo/fetus as compared to adulthood.

Key facts

NIH application ID
11216034
Project number
75N96024C00005-0-9999-1
Recipient
BATTELLE CENTERS/PUB HLTH RES & EVALUATN
Principal Investigator
DAWN FALLACARA
Activity code
N01
Funding institute
NIH
Fiscal year
2024
Award amount
$2,456,000
Award type
Project period
2024-09-16 → 2025-09-15