Functional Imaging Reserve in NeuroHIV

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to look at the brain's efficiency and ability to make up for deficits in the front of the brain to see if people living with HIV (PLWH) are still able to perform well on various cognitive tasks even though there are other underlying processes at work, like inflammation, that affect the brain in a negative way. Results of this study may provide insight into the pathophysiology of disease and may reveal arenas for future possible interventions in PLWH who have impaired neuropsychological performance.

Detailed Description
-----------------
This proposal systematically characterizes brain efficiency and recruitment in virologically suppressed persons living with HIV (PLWH) and demographically similar HIV uninfected (HIV-) controls. This proposal collects advanced functional neuroimaging that provide critical information about cerebral blood flow (CBF) and brain connectivity (functional connectivity strength; FCS); quantitative measures of immune dysfunction in the blood and cerebrospinal fluid (CSF) (immune activation and immune exhaustion); and neuropsychological performance testing. This overall goal of this proposal is to delineate the interplay between dysfunction in frontal networks and recruitment of compensatory networks that underlie the neuropsychiatric symptoms seen in PLWH.

Official Title
-----------------
Functional Imaging Reserve in NeuroHIV

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Diagnostic Test: Imaging
* Diagnostic Test: Serum Laboratory Tests
* Diagnostic Test: Lumbar Puncture


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 20 to 80 years old documented HIV infection for at least 1 year or confirmed HIV - status PLWH must be on stable cART regimen for at least 12 months with undetectable plasma HIV RNA (less than 50 copies per mL) at least 9 years of education able to provide informed consent if female, a negative pregnancy test and not breast feeding able to undergo an MRI scan Exclusion Criteria: significant neurological disorders (e.g. stroke, head injury with loss of consciousness for more than 5 minutes, developmental learning disability) active uncontrolled Axis I psychiatric disorder according to the DSM 5 current or history of substance use disorder (including, but not limited to amphetamines, cocaine, alcohol, opiates, and barbiturates) prescribed blood thinners allergic to lidocaine or similar anesthetic history of any bleeding disorder contraindication to MRI scanning (e.g. claustrophobia, pacemaker, etc.) pregnant or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Persons Living with HIV (PLWH)<br>Persons 20-80 years old with a documented HIV infection for at least 1 year, who are on a stable cART medication regimen for at least 1 year, and have an undetectable plasma HIV RNA (<50 copies/ml). | Diagnostic Test: Imaging<br>* 3T Prisma MRI<br>Diagnostic Test: Serum Laboratory Tests<br>* Blood (plasma and cellular) will be collected.<br>Diagnostic Test: Lumbar Puncture<br>* CSF will be collected<br>|
| HIV- Controls<br>Persons 20-80 years old with confirmed HIV- status matched to PLWH cohort with similar age, sex, education, and race. | Diagnostic Test: Imaging<br>* 3T Prisma MRI<br>Diagnostic Test: Serum Laboratory Tests<br>* Blood (plasma and cellular) will be collected.<br>Diagnostic Test: Lumbar Puncture<br>* CSF will be collected<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Efficiency and Recruitment - Determine the neuroimaging signatures of brain efficiency and recruitment in virologically suppressed PLWH. | The investigators will compare the recruitment of compensatory networks between the PLWH and HIV- controls using multiple linear regression. In exploratory analyses the investigators will compare the brain efficiency between PLWH and HIV-, using similar multiple regression models, controlling for confounders. Among PLWH, the investigators will study the association of brain efficiency with neuropsychological performance testing using multiple regression models. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Aging - Determine the effects of aging on brain efficiency and recruitment in virologically suppressed PLWH. | The investigators will compare the recruitment (response) between the four HIV age groups (HIV- <50 year old, HIV- ≥50 years old, HIV+ <50 years old, and HIV+ ≥50 years old) using a multiple regression (ANCOVA) model, adjusting for potential confounders (age, sex, education, past substance use, and CVD). The pairwise comparisons of primary interest is between the HIV- <50 years old and the HIV- ≥50 years old groups. Among the PLWH only, the investigators will compare the brain efficiency r (response) between the younger and older group using multiple regression, adjusting for potential confounders. Secondly, a mediation analysis will examine the role of immune dysfunction (activation and exhaustion) markers as mediators of this relationship. | 5 years |