Effect of Evolocumab on Coronary Endothelial Function

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.

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.

- 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.