While the widespread use of highly active antiretroviral therapy has markedly decreased cardiac morbidity and mortality in perinatally HIV-infected children, several studies have suggested subclinical abnormalities in echocardiographic measures of left ventricular structure and function. The goal of this study is to longitudinally evaluate the cardiovascular status of perinatally HIV-infected adolescents and young adults and to explore whether chronic inflammation and/or mitochondrial abnormalities are associated with echocardiographic and biomarker changes over time.
The specific aims of this study are to 1) to determine longitudinal changes of cardiovascular risk factors that were assessed ~6 years ago in the AMP (adolescents) and AMP Up (young adults) perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) cohorts of the Pediatric HIV/AIDS Cohort Study (PHACS); and to measure modified Pathobiological Determinants of Atherosclerosis in Youth or PDAY scores (a measure of aggregate cardiovascular risk) in HIV-infected adolescents longitudinally; and 2) To determine the role of systemic mitochondrial dysfunction in cardiovascular abnormalities and biomarkers by assaying mitochondrial DNA (mtDNA) copies/cell, oxidative phosphorylation (OXPHOS) enzyme activities, oxygen consumption (respiration), and mitochondrial oxidative stress. The results of this study can identify if there are perinatally HIV-infected adolescents and young adults, with long term exposure to HAART, which are at increased risk of future cardiovascular morbidities. If this is the case, the results of this study can inform various interventions in this increased cardiovascular risk group to decrease their future risk of adverse cardiovascular events.

Public Health Relevance

Heart failure in vertically HIV-infected children has decreased dramatically with the use of highly active antiretroviral therapy often referred to as an ?anti-HIV drug cocktail;? however, concerns continue regarding potential cardiac damage, even if the children do not currently have cardiac symptoms, which could lead to increased future cardiovascular risk in this population. The Cardiac Toxicity in Perinatally HIV-infected Adolescents and Young Adults, a Longitudinal Study will aim to find out if there is ongoing cardiac damage in this children and young adults over time. Findings from this study could inform potential clinical and lifestyle interventions to reduce future cardiovascular risk as well as cardiovascular screening recommendations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL137558-04
Application #
9977275
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Burns, Kristin
Project Start
2017-09-01
Project End
2021-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Pediatrics
Type
Schools of Medicine
DUNS #
038633251
City
Amherst
State
NY
Country
United States
Zip Code
14228