This project will investigate the ability of a novel MRI contrast agent to identify and quantitate ongoing monocyte/macrophage (M/MΦ)-mediated inflammation in the brains of HIV-infected individuals.

HIV-associated neurocognitive disorders (HAND) continue to be prevalent despite effective combination antiretroviral therapy (cART) and have a significant impact on morbidity and quality of life. Monocytes/macrophages (M/MΦ) are believed to play a critical role in the pathogenesis of HAND. Neuroimaging HIV research has not focused on assessing M/MΦ-mediated inflammation in the brain. Currently, no neuroimaging modality exists that can define the extent of active inflammation due to M/MΦ in HAND either as a clinical diagnostic tool or to assist in defining objective improvement in clinical trials addressing HAND. Ferumoxytol is an ultra-small iron oxide MRI contrast agent avidly taken up by circulating M/MΦ. The investigators hypothesize that ferumoxytol-based imaging can identify ongoing inflammation due to perivascular M/MΦ which is believed to represent a key pathologic correlate of HAND.

Inclusion Criteria:

• Age 40-65 years
• Plasma HIV RNA < 48 copies/ml (HIV+ subjects only)
• On stable cART >= 1 year (HIV+ subjects only)
• Global neuropsychological (NP) score <-0.5 in at least one cognitive domain known to be affected by HIV (neurocognitively impaired subjects only)
• Documentation of negative HIV infection by an FDA approved test (HIV- subjects only)

Exclusion Criteria:

• Active substance use
• History of myocardial infarct or stroke
• Diabetes
• Chronic hepatitis C virus (HCV) infection
• Uncontrolled major affective disorder, active psychosis, central nervous system disease that affects the brain structure, or other uncontrolled chronic medical condition that in the opinion of the investigator may impact NP testing or the study outcome
• Psychoactive or other medications which may impact NP testing
• Factors that preclude MRI
• Known hypersensitivity to ferumoxytol
• History of laboratory measurements consistent with an iron overload syndrome
• Medical conditions that require frequent blood transfusions
• Taking oral iron supplements
• Elevated iron levels
• Any condition, which in the opinion of the investigator, would compromise the subject's ability to participate
• Multiple drug allergies that may pose a greater risk of anaphylaxis associated with ferumoxytol
• Pregnant, unwillingness to practice birth control, or breastfeeding
• Unable to give informed consent