PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects

* INCLUSION CRITERIA: Subject groups: * Dopaminergic arm: * Group A: HIV-positive subjects with or without co-morbidities * Group B: HIV-negative subjects with co-morbidities * Group C: HIV-negative subjects without co-morbidities * Serotonergic arm: * Group D: HIV-positive subjects with or without co-morbidities * Group E: HIV-negative subjects with or without co-morbidities All Subjects (Groups A-E): 1. Men and women, 18-70 years of age 2. Ability to sign informed consent by the subject 3. Subjects may be enrolled in or have been discharged from IRB approved NIH protocols OR subjects may be referred from outside providers/institutions. 4. Has the ability to be seen by an outside medical doctor who provides care. All HIV-positive Subjects with or without co- morbidities (Groups A \[dopaminergic arm, n=25)\] and Group D \[serotonergic arm, n=20\]) 1. Known and documented HIV-1 infection 2. Plasma HIV-RNA BLD (\<100 copies/mm3) for greater than one year since the last available documented viral load measurement.. 3. At least one year of continuous ART prior to last documented suppressed viral load measurement and no history of ART modification or interruption since then. HIV-negative Subjects WITH Co-morbidities (Group B, n=25) 1. HIV-antibody negative 2. At least one or more of the following criteria: 1. Hypertension, as defined by treatment with medications for hypertension or with a systolic blood pressure at screening greater than or equal to 140mm Hg. 2. Diabetes mellitus, as defined by HgbA1C greater than or equal to 6.5% or known treatment for diabetes. 3. Hepatitis C infection as documented by lab results of a positive Hepatitis C antibody and/or detectable Hepatitis C viral load. Subjects who responded to HCV treatment (SVR) will be included. 4. History of previous but not current drug abuse. 5. History of previous but not current alcoholism (defined as alcohol intake that affect/affected the subject s work or home life). 6. Clinical atherosclerotic cardiovascular disease (ASCVD) (e.g. history of acute coronary syndromes, or myocardial infarction, stable or unstable angina, coronary or other arterial revascularization or peripheral arterial disease of atherosclerotic origin) and/or 10-year heart disease risk score (ASCVD risk score) \>7.5% (7.5 % score is the threshold for starting statin therapy as per the 2013 American College of Cardiology \[ACC\] / American Heart Association \[AHA\] guidelines). HIV-negative Subjects WITHOUT co-morbidities (Group C, n=25) 1. HIV-antibody negative 2. No history of any of the following: 1. Hypertension, as defined by treatment with medications for hypertension or with a systolic blood pressure at screening greater than or equal to 140mm Hg. 2. Diabetes mellitus, as defined HgbA1C greater than or equal to 6.5% or treatment for diabetes. 3. Hepatitis C infection as documented by lab results of positive Hepatitis C antibody and/or detectable Hepatitis C viral load. Subjects who responded to HCV treatment (SVR) will not be included. 4. History of previous drug abuse. 5. History of previous alcoholism. Alcoholism is based on alcohol having affected the subject s work or home life. 6. Clinical ASCVD (e.g. history of acute coronary syndromes, or myocardial infarction, stable or unstable angina, coronary or other arterial revascularization or peripheral arterial disease of atherosclerotic origin) and/or 10-year heart disease risk score (ASCVD risk score) \>7.5% (7.5 % score is the threshold for starting statin therapy as per the 2013 ACC/AHA guidelines 35). 7. Any other disease entities including chronic infections (e.g. Hepatitis B, Lyme disease), neurological diseases (e.g. Multiple sclerosis, vasculitis) or systemic diseases (e.g. Sjogren s diseases, sarcoidosis, systemic lupus erythematosus \[SLE\]) that in the opinion of the investigator would be considered a significant co-morbidity. HIV-negative Subjects with or without co- morbidities (Group E, n=20) 1\. HIV-antibody negative EXCLUSION CRITERIA: All Subjects (Groups A-E): 1. Illness or other condition that, in the opinion of the PI, may interfere with study participation at the time of enrollment, including known history of significant intracranial structural damage such as previous stroke(s) or history of intracranial benign or malignant tumors. 2. Conditions other than HAND associated with cognitive impairment or dementia such as Alzheimer s, Parkinson s disease, head injury with loss of consciousness \>30 minutes, or seizure disorders. 3. A positive screening result for psychiatric diseases that are known to affect the dopaminergic or serotonergic systems. 4. Current substance abuse that would interfere with PET scan results at the investigators discretion. 5. Medications: use of any drug with known dopaminergic or serotonergic activity within 6 months prior to planned imaging date(s). 6. Pregnant or Lactating women: Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to study entry. Pregnancy testing will also be performed in enrolled female participants prior to any radiation exposure. 7. Prior or planned/anticipated exposure to radiation due to clinical care or participation in other research protocols, which would exceed the recommended acceptable annual limit of radiation exposure once accounting for the requirements of the current study. Additional Exclusion Criteria for the Dopaminergic Arm (Groups A, B and C): 1. Use of any of the following drugs within 6 months from planned imaging date(s): 1. Haloperidol (increased intracerebral dopamine turnover caused by haloperidol may result in increased accumulation of 18F-DOPA) 2. Monoamine oxidase (MAO) inhibitors (may result in increased accumulation of 18F-DOPA in the brain) 3. Reserpine (reserpine-induced depletion of the contents of intraneuronal vesicles may prevent retention of 18F-DOPA in the brain) 4. Carbidopa/LDOPA (LDOPA competes with 18F-DOPA for DOPA decarboxylase activity) 2. Allergy to carbidopa Note that HBV is not an exclusion criterion for groups A, B, D or E since it s not known to have direct CNS pathology in the absence of advanced liver disease and cirrhosis.