Contemporary cohorts of people living with HIV (PLWH) have a ~ 2.5-fold increased relative risk of heart failure versus matched controls. The predominant type of heart failure among PLWH is heart failure with a preserved ejection fraction (HFpEF). This type of heart failure is typically preceded by diastolic dysfunction, a condition in which the left ventricle of the heart stiffens, resulting in delayed relaxation and increased filling pressures. Among PLWH, the prevalence of diastolic dysfunction is strikingly high: 43%. Once diastolic dysfunction has progressed to overt HFpEF, no good therapeutic options exist. Thus, strong imperatives exist to test rational, safe strategies which may preserve diastolic function and prevent progression to overt heart failure among aging PLWH on ART. There are two key processes which likely contribute to the development of diastolic dysfunction in HIV. The first is myocardial fibrosis, a condition in which excess collagen is deposited in the myocardial structural space. The second is myocardial steatosis, a condition in which triglycerides are ectopically deposited within cardiomyocytes. Myocardial fibrosis and myocardial steatosis are both increased among PLWH, in relation to diastolic dysfunction. We postulate that PLWH without overt heart failure, statin therapy will reduce the progression of myocardial fibrosis and myocardial steatosis, preserving cardiac function. Our primary hypothesis is that statin effects to dampen systemic immune activation and inflammation will translate to reduced in situ myocardial inflammation and, in turn, reduced myocardial fibrosis. We will also test an alternate hypothesis that statin effects to improve lipid metabolism will result in reduced ectopic fat deposition in the heart. Cardiac magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) represents a gold-standard approach with which to test our hypotheses. We propose an observational cardiac MRI/MRS-based study, CARDIAC-MR, integrated with an ongoing randomized trial of pitavastatin vs. placebo (REPRIEVE). From 8 REPRIEVE sites, we will co-enroll 130 PLWH aged 40-75 without known heart failure. Outside of REPRIEVE, we will orchestrate additional study visits at entry and 24 months. At these visits, participants will undergo cardiac MRI/MRS, as well as targeted metabolic and immune phenotyping. Our work will answer scientific questions relevant to heart failure prevention in HIV which will not otherwise be addressed in REPRIEVE. If we confirm our hypothesis that statins forestall progression of myocardial fibrosis and/or fat among PLWH, we will have found the first effective strategy to preserve cardiac function in HIV. Even in the case of null statin effects on fibrosis/fat, our baseline characterization of pathologic pathways predisposing to cardiac dysfunction will help identify future targeted strategies geared toward heart failure prevention in HIV. Given that heart failure is a highly morbid, age-related comorbidity to which PLWH are particularly vulnerable, our work will have significant clinical implications to improve the lives of at-risk individuals aging with HIV.

Public Health Relevance

Individuals living with HIV have higher rates of heart failure than individuals without. We will identify why individuals living with HIV develop heart failure and test whether statins, a type of drug typically used to lower cholesterol, can protect the heart muscle and improve the way the heart functions among individuals with HIV.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Sopko, George
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Mahmood, Syed S; Fradley, Michael G; Cohen, Justine V et al. (2018) Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol 71:1755-1764
Ganatra, Sarju; Neilan, Tomas G (2018) Immune Checkpoint Inhibitor-Associated Myocarditis. Oncologist 23:879-886
Gogia, Shawnbir; Coromilas, Alexandra; Regan, Susan et al. (2018) Cardiovascular Risk Profile of Transgender Women With HIV: A US Health Care Database Study. J Acquir Immune Defic Syndr 79:e39-e41
Alvi, Raza M; Neilan, Anne M; Tariq, Noor et al. (2018) Protease Inhibitors and Cardiovascular Outcomes in Patients With HIV and Heart Failure. J Am Coll Cardiol 72:518-530
Mahmood, Syed S; Sullivan, Ryan J; Reynolds, Kerry L et al. (2018) Reply: Immunosuppression Does Not Reduce Antitumor Efficacy. J Am Coll Cardiol 72:702
Kohli, Puja; Staziaki, Pedro V; Janjua, Sumbal A et al. (2018) The effect of emphysema on readmission and survival among smokers with heart failure. PLoS One 13:e0201376
Foldyna, Borek; Fourman, Lindsay T; Lu, Michael T et al. (2018) Sex Differences in Subclinical Coronary Atherosclerotic Plaque Among Individuals With HIV on Antiretroviral Therapy. J Acquir Immune Defic Syndr 78:421-428
Addison, Daniel; Lawler, Patrick R; Emami, Hamed et al. (2018) Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer. J Stroke 20:71-79
Srinivasa, Suman; Lu, Michael T; Fitch, Kathleen V et al. (2018) Epicardial adipose tissue volume and cardiovascular risk indices among asymptomatic women with and without HIV. Antivir Ther 23:1-9
Ferreira de Souza, Thiago; Quinaglia A C Silva, Thiago; Osorio Costa, Felipe et al. (2018) Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease. JACC Cardiovasc Imaging 11:1045-1055

Showing the most recent 10 out of 12 publications