Mechanisms of Diastolic Dysfunction Among Persons With HIV Compared With Non-HIV Control Subjects

Mechanisms of Diastolic Dysfunction Among Persons With HIV Compared With Non-HIV Control Subjects

In this study, investigators plan to test two potential mechanisms contributing to diastolic dysfunction among asymptomatic persons with HIV who are on cART. The first proposed mechanism is that heightened systemic immune activation/inflammation in HIV contributes to myocardial inflammation, which in turn promotes myocardial fibrosis. The second mechanism is that ectopic fat deposition (increased visceral adiposity) in HIV relates to increased intramyocardial lipid content, which in turn contributes to diastolic dysfunction. Both HIV positive and HIV-negative participants will undergo cardiac MRI/ MRS imaging studies for evaluation of myocardial fibrosis, myocardial inflammation, and intramyocardial lipid content. Traditional markers of CVD risk, inflammatory markers/immune, hormonal markers, and markers of myocardial stretch/injury will be assessed in relation to cardiac MRI/MRS outcomes. Additionally, a small subset of participants with HIV will undergo longitudinal evaluations to assess effects of a clinically prescribed hormonal therapy on myocardial structure and function.

HIV positive subjects

Inclusion Criteria:

• age ≥40 and ≤75 years
• documented HIV infection
• participant report that combination antiretroviral therapy (cART) (any regimen) has been taken stably without > 4 week interruption for at least 180 days prior to study entry (report of switching regimens in that time frame is permissible)

Exclusion Criteria:

• CD4 < 100 cell/mm3
• current active AIDS-defining illness
• current active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus [HPV], or HCV)
• current active cancer
• clinical ASCVD, as defined by 2013 ACC/AHA guidelines (including previous diagnosis of AMI, ACS, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, PAD), by subject report
• clinical diagnosis of HFpEF or HFrEF, by subject report
• diagnosed DM on antihyperglycemic medication
• current, active use of immune suppressant medication including oral or intravenous corticosteroid or injectable biologic (oral ASA or NSAID use permitted)
• eGFR <45 ml/min/1.73 m2 calculated by CDK-EPI
• standard contraindications to MRI procedure based on MGH MRI Patient Procedure Screening Form - including history of severe allergy to gadolinium
• use of lipid lowering agents including statin drugs, fibrates, ezetimibe, red yeast rice, niacin or omega-3 fatty acids (>3 grams/day in standalone formulations) in the 90 days prior to study entry
• use of ACE inhibitor, ARB, or aldosterone receptor blocker in the 90 days prior to study entry
• pregnancy or breastfeeding (female subjects of reproductive potential)
• other medical, psychiatric, or psychological condition that, in the opinion of the study investigator, would interfere with completion of study procedures

HIV negative subjects:

Inclusion Criteria:

• age ≥40 and ≤75 years

Exclusion Criteria:

• HIV infection
• current active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus [HPV], or HCV)
• current active cancer
• clinical ASCVD, as defined by 2013 ACC/AHA guidelines (including previous diagnosis of AMI, ACS, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, PAD), by subject report
• clinical diagnosis of HFpEF or HFrEF, by subject report
• diagnosed DM on antihyperglycemic medication
• current, active use of immune suppressant medication including oral or intravenous corticosteroid or injectable biologic (oral ASA or NSAID use permitted)
• eGFR <45 ml/min/1.73 m2 calculated by CDK-EPI
• standard contraindications to MRI procedure based on MGH MRI Patient Procedure Screening Form - including history of severe allergy to gadolinium
• use of lipid lowering agents including statin drugs, fibrates, ezetimibe, red yeast rice, niacin or omega-3 fatty acids (>3 grams/day in standalone formulations) in the 90 days prior to study entry
• use of ACE inhibitor, ARB, or aldosterone receptor blocker in the 90 days prior to study entry
• pregnancy or breastfeeding (female subjects of reproductive potential)
• other medical, psychiatric, or psychological condition that, in the opinion of the study investigator, would interfere with completion of study procedures