Functional Imaging Reserve in NeuroHIV (FIRN)

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Diagnostic test: Imaging; Diagnostic test: Serum Laboratory Tests; Diagnostic test: Lumbar Puncture

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.

• Study Type: Observational
• Enrollment (Actual): 284

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult persons living with HIV (PLWH) and demographically similar healthy HIV- controls

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Persons Living with HIV (PLWH); 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; 3T Prisma MRI; Diagnostic test: Serum Laboratory Tests; Blood (plasma and cellular) will be collected.; Diagnostic test: Lumbar Puncture; CSF will be collected
HIV- Controls; Persons 20-80 years old with confirmed HIV- status matched to PLWH cohort with similar age, sex, education, and race.	Diagnostic test: Imaging; 3T Prisma MRI; Diagnostic test: Serum Laboratory Tests; Blood (plasma and cellular) will be collected.; Diagnostic test: Lumbar Puncture; CSF will be collected

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: University of California, San Diego; National Institutes of Health (NIH); Temple University; University of Missouri, St. Louis
• Investigators: Principal Investigator: Beau M Ances, MD, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Biopsy; Physical Phenomena; Electromagnetic Phenomena; Magnetic Phenomena; Diagnostic Techniques, Neurological; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Spinal Puncture; X-Rays
• Other Study ID Numbers: 201805047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data might be shared when the study has closed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No