Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV

Survival in people with HIV has significantly improved with the use of antiretroviral therapy
(ART) but HIV+ people now experience an increasing burden of chronic diseases, including
coronary atherosclerosis and coronary artery disease (CAD). HIV patients manifest an
increased risk of CAD and its consequences possibly due to interplay of inflammation with
traditional risk factors (smoking, high cholesterol, and poor diet), some of the latter
accentuated by ART.

What the investigators are studying in this program is the function of the coronary arteries
and in particular the inner lining of the arteries called the endothelium in patients with
HIV. The endothelium has several important functions; one of them is that under conditions of
stress it releases a substance called nitric oxide which increases the size of the artery and
increases blood flow. When it is not functioning normally the artery does not increase as
much and blood flow does not increase during stress.

The investigators study coronary artery function with magnetic resonance imaging, or MRI. MRI
is a method of obtaining images of what is happening inside the body. MRI does not involve
radiation, x-ray, or injection of contrast. The investigators can measure flow in the artery
and the dimension of the artery at rest and with a handgrip stress and learn the extent to
which the artery dilates and flow increases with the stress. The investigators believe that
inflammation can interfere with normal function and that by decreasing inflammation abnormal
endothelial function may be improved.

Colchicine is an anti-inflammatory agent approved by the Food and Drug Administration (FDA)
to treat arthritis and some other conditions. This drug is not approved for use to suppress
inflammation in patients with coronary artery disease and improve coronary artery endothelial
function. The FDA is allowing the use of colchicine or a placebo in this research study.

This study will involve 24 weeks of colchicine or placebo and 3 Magnetic Resonance Imaging
(MRI) scans of the heart and other study procedures.

Inclusion Criteria:

- Patients of either gender who are 21 years of age (no upper age limit), HIV positive
and taking stable ART (no change in ART regimen in last 3 months),

- HIV viral load <100 copies/mL (plasma HIV RNA concentration),

- Abnormal CEF at baseline (<7ml/min change in CBF during IHE as compared to resting
value).

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) or indwelling metallic projectiles,

- History of clinical CAD, including acute coronary syndrome, myocardial infarction or
revascularization,

- Resting ECG with evidence of Q wave myocardial infarction,

- Pregnant women,

- Recent history, within the past 3 months, of cocaine or heroin use,

- Moderate or greater renal impairment (estimated glomerular filtration rate <45ml/min),

- Moderate-severe hepatic disease (elevation in hepatic transaminases >3x upper limit of
normal),

- Leukopenia (<3000/mm3) or thrombocytopenia (<100,000/mm3),

- CD4<200 cell/mm3,

- Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative
colitis or Crohn's disease,

- Requirement for, or intolerance to, colchicine,

- Women of childbearing potential (even if using oral contraceptive agents) or intention
to breastfeed,

- Chronic, continuous use of oral or IV steroid therapy or other immunosuppressive or
biologic response modifiers or anti-inflammatory agents (chronic NSAIDs or
acetylsalicylic acid (ASA) >81mg daily),

- History of chronic pericardial effusion, pleural effusion, ascites or peripheral
neuropathy manifested by both signs and symptoms,

- Taking protease inhibitors (PI), cobicistat, or CYP3A4 inhibitors.