Mild Neurocognitive Disorder in HIV Infection of the Brain

1. Subjects must be between 18 and 60 years of age.

   2. Capable of providing informed consent.
   3. Ambulatory at initial visit.
   4. Speak English fluently

   5. For HIV seropositive subjects:

      1. Confirmation of HIV antibody status by ELISA and Western Blot
      2. Documented HIV-infection for at least one year
      3. On a stable antiretroviral regimen that includes a protease inhibitor for at least 3 months and have a viral load \< 400 copies/mL.
      4. Have a primary care physician.

Specific inclusion criteria for mild neurocognitive disorder are as follows:

1. Subject has an acquired mild-to-moderate impairment in cognitive function documented by a score of at least 1 SD below demographically corrected norms on testing of at least two different cognitive domains.
2. The cognitive impairment interferes, at least mildly, with activities of daily living, as determined by neuropsychological interview.
3. The impairment does not meet DSM-IV criteria for delirium or dementia.
4. The impairment is not fully explained by co-morbid conditions.

EXCLUSION CRITERIA:

1. Current Axis I psychiatric illness or severe systemic disease (other than HIV and MND) based on history and physical exam that would make study participation unsafe in the opinion of the investigators.
2. Current alcohol use greater than 14 drinks per week for men and 7 drinks per week for women.
3. Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL, serum calcium \<12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT 1.5 upper limit of normal.
4. EKG finding consistent with ischemic heart disease unless there is documentation of normal cardiac function (e.g., normal stress test or echocardiogram results).
5. Previous research radiation exposure (X-rays, PET scans etc.) that, with the study PET scans, would exceed annual research limits.
6. Pregnancy or breast feeding.
7. Evidence of brain disease such as stroke, tumor, epilepsy, traumatic brain injury, or any neurodegenerative disease on history or on screening MRI.
8. Inability to lay on his/her back for long periods, severe claustrophobia, pacemaker, or other contraindication for MRI.
9. More than moderate hypertension, defined as blood pressure greater than or equal to 160/95 at the time of screening.
10. Current use of illicit drugs based on positive result on urine screen for illicit drugs at the time of screening.
11. Subjects taking medications, other than anti-retroviral drugs, that are known substrates of P-gp that cannot be safely discontinued for this study. Anti-retroviral drugs, particularly protease inhibitors such as ritonavir, that are P-gp substrates are allowed.

Note: The rationale for the exclusion criteria for alcohol use is to avoid alcohol-related cognitive impairment as a confounding factor.