Use of 99mTc Tilmanocept for Imaging Arterial Inflammation

Detailed Description:

Patients with HIV have been shown to have increased atherosclerotic risk compared to
age-matched controls, and this risk is thought to be related to increased systemic immune
activation. Specifically, systemic immune activation may contribute to destabilizing coronary
atherosclerotic plaque, leading to plaque rupture and myocardial infarction. This study is
intended to measure arterial uptake of the macrophage specific marker 99mTc-Tilmanocept using
single photon emission computed tomography, applied initially to a group of HIV-infected
patients with known subclinical coronary atherosclerosis on CCTA. Moreover, traditional
markers of CVD risk and inflammatory markers will be assessed in relation to CV imaging
outcomes. Positive findings in the index HIV group with known subclinical atherosclerosis
will prompt subsequent study of three comparison groups, as above.

HIV infected subjects with known subclinical atherosclerosis:

Inclusion criteria:

- men and women, ages 18+, with documented HIV infection

- current use of antiretroviral therapy (ART), with no changes to regimen within last 3
months

- history of subclinical atherosclerosis on CCTA

Exclusion criteria:

- pregnancy or breastfeeding

- known active opportunistic infection requiring ongoing medical therapy (not including
Hepatitis B/C)

- CD4 count < 50 cells/mm3

- history of angina, myocardial infarction, acute coronary syndrome, or coronary artery
stenting or surgery

- recent and/or current treatment with prescription, systemic steroids or
anti-inflammatory/immune suppressant medical therapies

- current use of statin or use of statin for > 1 month within the last 6 months

- known allergy to dextrans and/or DPTA and/or radiometals and/or iodinated contrast
media

- eGFR < 60 ml/min/1.73 m2 calculated by CDK-EPI

- contraindications to beta blockers or nitroglycerin

- significant radiation exposure (>2 CT angiograms) received within the past 12 months

- BMI > 35 kg/m2 or waist circumference > 70 cm (scanner limitations)

HIV infected subjects without known subclinical atherosclerosis:

Inclusion criteria:

- men and women, ages 18+, with documented HIV infection

- current use of antiretroviral therapy (ART), with no changes to regimen within last 3
months

- history of clean aorta/ coronaries on CCTA

Exclusion criteria:

- Same as exclusion criteria for HIV infected subjects with known subclinical
atherosclerosis

HIV negative subjects with known subclinical atherosclerosis:

Inclusion criteria:

- men and women, ages 18+, without documented HIV infection

- history of subclinical atherosclerosis on CCTA

Exclusion criteria:

- pregnancy or breastfeeding

- history of angina, myocardial infarction, acute coronary syndrome, or coronary artery
stenting or surgery

- recent and/or current treatment with prescription, systemic steroids or
anti-inflammatory/immune suppressant medical therapies

- current use of statin or use of statin for > 1 month within the last 6 months

- known allergy to dextrans and/or DPTA and/or radiometals and/or iodinated contrast
media

- eGFR < 60 ml/min/1.73 m2 calculated by CDK-EPI

- contraindications to beta blockers or nitroglycerin

- significant radiation exposure (>2 CT angiograms) received within the past 12 months

- BMI > 35 kg/m2 or waist circumference > 70 cm (scanner limitations)

HIV negative subjects without known subclinical atherosclerosis:

Inclusion criteria:

- men and women, ages 18+, without documented HIV infection

- history of clean aorta/coronaries on CCTA

Exclusion criteria:

- Same as exclusion criteria for HIV negative subjects with known subclinical
atherosclerosis