Effect of Evolocumab on Coronary Endothelial Function

The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.

To evaluate the effect of the PCSK9 inhibitor evolocumab on coronary and systemic endothelial function, systemic biomarkers of endothelial function and of inflammation, and echocardiographic measures of left ventricular diastolic and systolic properties in subjects who are HIV+. Potential participants will be asked to undergo a screening MRI exam. Those who have evidence of coronary endothelial dysfunction on the MRI exam will receive evolocumab 420 mg sq (the dose that is approved for treatment of hypercholesterolemia) following the screening exam and again at one month. Repeat MRI and ultrasound measures of coronary and systemic endothelial function, as well as serum markers of endothelial function and inflammation, and echocardiographic measures of diastolic and systolic left ventricular function will be obtained at one and six weeks following the first administration of evolocumab.

The investigators will test the hypotheses that PCSK9 inhibition improves endothelial function measured non-invasively on MRI and systemic markers of inflammation at one week (+/- 3 days) and six weeks after initiation of the PCSK9 antibody.

Eligibility Criteria:
Inclusion Criteria:

* Participants of either gender who are \>21 years of age (no upper age limit)
* HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)
* Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)
* Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (\<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).
* Lipids at screening visit: Fasting LDL-C \>70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG\<500 mg/dL (TG=Triglycerides)
* Permission of treating physician

Exclusion Criteria:

* Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.
* Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),
* History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.
* Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.
* Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.
* History of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any recreational drugs within 6 months prior to screening.
* Renal impairment defined by estimated glomerular filtration rate \<45 ml/min.
* Moderate-severe hepatic disease (elevation in hepatic transaminases \>3x upper limit of normal, ULN) or direct bilirubin \>3.0 X ULN at screening.
* Cluster of differentiation 4 (CD4)\<200 cell/mm3
* Congestive heart failure, New York Heart Association functional class III or greater, or left ventricular ejection fraction measured by imaging known to be \<30%. (Imaging not required for study inclusion).
* History of allergic or anaphylactic reaction to any therapeutic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies
* Active phase hepatitis. Stable patients with hepatitis B or C infection \>3 years before randomization are eligible.