Brain Imaging for HIV-Associated Thinking and Mood Disorders

With combination antiretroviral therapy, HIV/AIDS has been transformed from a progressive,
usually fatal infection to a manageable chronic condition. Yet, HIV associated neurocognitive
disorders (HAND) pose a significant clinical problem, even among patients with controlled HIV
viremia. There is evidence of accelerated vascular aging and other vascular disorders in
HIV-infected (HIV+) people, and studies suggest an association between vascular disorders and
unfavorable neurocognitive outcomes. Thus, one possible contributing factor to the high rates
of HANDs and depression could be vascular dysfunction, similar to vascular depression and
vascular dementia that occur in elderly non-HIV+ individuals. One commonly used diagnostic
marker of vasculopathy is thickening of the vessel wall. Multiple studies have already
established the correlation between vessel wall thickening and vascular disease
manifestations. This prospective observational study aims to examine the relationships
between neurocognitive and depression outcomes and vessel wall thickness as a marker of
vascular disease in HIV+ adults. We will be using neuropsychological testing, brain imaging,
blood biomarkers, and state-of-the-art high-resolution MR imaging of the carotid vessel
walls. HIV infected patients (n=40) and HIV-negative controls (n=40) will be recruited.
Participants who consent to longitudinal follow-up will be followed for two years with
clinical evaluations every 6 months and repeat imaging studies at 12 and 24 months. Cross
sectional data analysis will compare markers of vascular and neurocognitive disorders between
HIV-infected and HIV-negative participants. The longitudinal data analysis will assess and
compare the temporal progression of vascular disease (imaging and blood biomarker findings)
in relation to changes in neurocognitive and depression scores in both groups.

- INCLUSION CRITERIA:

Inclusion criteria for all participants:

1. Age 25-61 years.

2. Willingness to allow stored samples, human leukocyte antigen (HLA) testing, and future
genetic testing.

3. Hemoglobin less than or equal to 9.0 g/dL, HCT less than or equal to 28%, platelets
less than or equal to 50,000/microL.

4. English language fluency (required for neuropsychological testing).

Additional inclusion criteria for HIV+ participants:

1. Documented HIV infection by standard HIV testing. Prior documentation of HIV- antibody
status at the NIH will be accepted in lieu of repeat testing.

2. HIV viral load below the limit of detection on combination antiretroviral therapy for
less than or equal to 1 year.

3. Under the care of a primary care physician.

Additional inclusion criteria for HIV-negative participants:

1. HIV-antibody negative.

EXCLUSION CRITERIA:

Exclusion criteria for all participants:

1. Contraindication to MRI scanning, including pacemakers or other implanted electrical
devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips
on the wall of a large artery), metallic prostheses (including metal pins and rods,
heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or
shrapnel fragments.

2. Subjects with a condition precluding entry into scanner and acquisition of scans
(e.g., morbid obesity, claustrophobia, back pain, motion disorders).

3. Glomerular filtration rate <45 mL/min/1.73 m(2) as estimated using the Modified Diet
in Renal Disease equation.

4. Allergy to qadolinium (MRI contrast)

5. Evidence of current or prior central nervous system opportunistic infection(s) and/or
space-occupying lesions such as primary CNS lymphoma.

6. Prior history of intrathecal chemotherapy or radiation therapy to the brain.

7. History of or current diagnosis of systemic vasculitis.

8. Active systemic infection or malignancy requiring therapy.

9. Psychiatric condition interfering with ability to participate in study procedures or
provide informed consent.

10. Patient or provider report of alcohol or drug abuse ongoing or within 3 months prior
to participation.

11. Sickle cell disease (due to known association with vasculopathy).

12. Systolic blood pressure less than or equal to 180 mmHg at screening.

13. Persons infected with hepatitis C virus (HCV) who are being treated or planning to
seek treatment for HCV.

14. Women who are lactating, pregnant, or actively seeking to become pregnant.

15. Other known clinical condition or conditions discovered on MRI that, at the discretion
of the investigators, precludes serial clinical, neuropsychological, or imaging
evaluation.

Additional exclusion criteria for HIV+ participants

1. HIV acquired perinatally (due to potential effects of HIV and antiretroviral therapy on
neurocognitive and vascular development).