Cardiometabolic Effects of Eplerenone in HIV Infection

HIV-infected individuals are at higher risk than uninfected people for developing
cardiovascular disease. Visceral adipose tissue is also increased in HIV-infected people
compared to uninfected individuals. Animal studies suggest that blockade of the
mineralocorticoid receptor (MR) may have beneficial effects on cardiovascular and metabolic
parameters via inhibition of adipocyte differentiation and triglyceride accumulation. We will
examine the effects of the MR antagonist eplerenone (50 mg daily) on HIV-infected adults with
abdominal fat accumulation in a 24-week, open-label, proof-of-concept study. Magnetic
resonance imaging will be conducted at screening and the final study visit to evaluate
cardiac and hepatic steatosis. We anticipate that blocking the effects of increased
aldosterone secretion with eplerenone will significantly reduce intramyocardial lipid content
and hepatic steatosis in this population. These effects may be accompanied by decreases in
visceral adipose tissue, and improvements in dyslipidemia and inflammation, thereby improving
cardiovascular health.

- INCLUSION CRITERIA:

1. Increased waist circumference on the basis of National Cholesterol Education
Program guidelines (> 102 cm in men and > 88 cm in women)

2. Hepatic steatosis established by hepatic MRI greater than or equal to 5% and/or
liver biopsy within the last 12 months

3. HIV-infected, HIV viral load < 50 copies/mL and no change in ART regimen for at
least 3 months

4. Age greater than or equal to 18 and less than or equal to 75 years

5. Agree to have samples stored for future research

EXCLUSION CRITERIA:

1. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2, serum creatinine >
1.5 mg/dL

2. Serum potassium > 5.5 mEq/L, alanine aminotransferase > 2.5 times the upper limit of
normal, hemoglobin (Hgb) < 11 g/dL

3. Uncontrolled hypertension: systolic blood pressure greater than or equal to 160 mm Hg
or diastolic blood pressure greater than or equal to 100 mm Hg

4. A blood pressure < 90mmHg systolic or < 50mm Hg diastolic

5. Screening EKG with a significant heart block (e.g. PR > 300 ms) or an EKG determined
significant by Cardiology consult.

6. Current hepatitis C infection, unless there has been a sustained virologic response
for at least 12 months

7. Type 2 diabetes with microalbuminuria

8. Current or prior steroid use within past 6 months (except short-course or single-dose
administration). Stable use of inhaled or nasal steroids are allowed.

9. Use of angiotensin converting enzyme (ACE) inhibitors, angiotensin reporter blockers
(ARBs), potassium-sparing diuretics, and other medications that may increase the risk
of hyperkalemia

10. Use of potassium supplementation or other medications known to increase potassium

11. Concomitant use of strong inhibitors and/or inducers ofof cytochrome P450 isozyme
(CYP)3A4

12. If receiving testerone, estrogen or progesterone therapy, must be on a stable dose for
at least 3 months.

13. Current use of growth hormone or growth hormone-releasing hormone

14. Current serious viral, bacterial, or other infection (excluding HIV)

15. Current active substance abuse/dependence

16. Substantial history of cardiovascular disease, including prior myocardial infarction
(MI), congestive heart failure, or stroke

17. Contraindication to MRI

18. Pregnant or planning to become pregnant

19. Breastfeeding

20. Any condition that, in the opinion of the PI, may substantially increase the risk of
participation