Evaluation of HIV-associated Cardiac Dysfunction in Women

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 DESCRIPTION (provided by applicant): The advent of combination antiretroviral therapy (cART) has led to marked decreases in AIDS- related mortality in people with HIV infection. Although this has been accompanied by reduction of severe dilated cardiomyopathy associated with late-stage HIV, echocardiographic studies of HIV-infected cohorts in the cART era have highlighted pronounced increases in the prevalence of milder forms of LV systolic dysfunction and, particularly, diastolic dysfunction. Given the young age of such cohorts, and the advancing age of people living with HIV, these echo findings herald a potential upsurge of HF in this population. Moreover, novel cardiac magnetic resonance (CMR) techniques have shown interstitial fibrosis and intramyocardial triglyceride (TG) content to be increased in the setting f cardiovascular and metabolic risk factors, and to correlate with impaired LV function. Such risk factors are well-known to be associated with HIV and its treatment, and modest-sized CMR studies of HIV-infected patients have recently demonstrated increased myocardial fibrosis and TG content, along with depressed myocardial mechanics. Like the majority of available echo studies, these CMR studies did not focus on women, and are limited both by inclusion of healthy volunteers as controls, and by lack of detailed longitudinal assessment of HIV-related factors or treatment. Meanwhile, the development of speckle-tracking echo assessment of myocardial deformation now permits more accurate evaluation of subclinical cardiac dysfunction using a widely applicable non-invasive technique. We propose to leverage the largest and longest prospective cohort of HIV-infected and well-matched uninfected women, the Women's Interagency HIV Study, to build on our previous echo study among Bronx and Brooklyn participants, and perform repeat echoes approximately 12 years later. This will allow the first long-term longitudinal assessment of LV dysfunction in HIV-infected and uninfected women, and a well-sized evaluation of myocardial deformation in such individuals. This will be complemented by CMR assessment of interstitial fibrosis and myocardial TG content, as well as infarct. Using repeated measures of HIV-specific exposures and ART, and added biomarkers of cardiac stress, inflammation and lipid dysregulation, this proposal stands to provide important new knowledge concerning the role of HIV infection and related factors in subclinical myocardial dysfunction and disease. In so doing, the proposed project will identify strategies and future research to avert the potential rise in symptomatic HF that threatens the HIV-infected population in the cART era.