The ENCHANTMENT HIV Study

This is a 6-month study enrolling persons with HIV with no known history of heart disease. Participants will be screened for early signs of heart failure using cardiac ultrasound (cardiac transthoracic echocardiography or cardiac TTE). Those participants who have early changes in the structure and function of the heart and may be at future risk for heart failure will be enrolled into the study. Additional imaging of the heart will occur using cardiac magnetic resonance imaging (cardiac MRI). Following baseline studies, participants will either receive a medication called sacubitril/valsartan or placebo for 6 months. Sacubitril/valsartan in an FDA approved medication currently being used for heart failure with reduced ejection fraction in the general population, and we are evaluating whether this medication could be useful to reduce HIV-related heart failure with preserved ejection fraction. Sacubitril/valsartan is an oral medication taken twice daily that may block aldosterone hormone and increase natriuretic peptide hormone. Overall, this study aims to investigate the effect of sacubitril/valsartan on measures of heart disease related to inflammation, structure and function of the heart muscle in HIV using cardiac TTE and cardiac MRI imaging as well as blood markers of heart failure and inflammation.

Inclusion criteria

• Antiretroviral therapy use for >12 months
• HIV Viral Load <200 copies/mL
• Left Ventricular Ejection Fraction>50%
• Demonstration of one or more criteria for myocardial dysfunction on cardiac transthoracic echocardiogram, relevant to the progression of heart failure with preserved ejection fraction:

• Left Atrial Volume Index > 28 mL/m2
• Global Longitudinal Strain <18%
• Left Ventricular Mass Index > 95g/m2 (female), 115 g/m2 (male)

Exclusion criteria

• Known history of congestive heart failure or valvular disease
• Recent cardiac event or stroke within 3 months
• Current medication use acting along the RAAS pathway (ACEi, ARB, MR blockade, direct renin inhibitor), potassium (K) supplementation or diuretic
• Angioedema to ACEi or ARB
• SBP<100 mmHg
• Medication suspected to have contraindication with active study drug
• Steroid use within last 3 months
• Uncontrolled diabetes requiring insulin and/or HbA1c > 7.5%
• Creatinine (Cr)>1.5 mg/dL and estimated GFR<60 mL/min/1.73m2
• K>5.5 mEq/L
• Hemoglobin <10.0 g/dL
• Known liver disease or ALT>3x upper limit normal
• Pregnant, actively seeking pregnancy or breastfeeding
• Estrogen, progestin derivative, or other sex steroid use within 3 months. Stable physiologic testosterone replacement (> 3 months) is acceptable
• Current bacterial or other infection
• Active substance abuse
• Known reaction to gadolinium