Examining thinking and memory issues in people with HIV

An Evaluation of HIV-associated Neurocognitive Disorders (HAND) in Virologically Controlled Patients

This study is trying to see how HIV affects thinking and memory in people whose virus is under control, by comparing them to healthy volunteers over 20 years.

Quick facts

• Study type: Observational
• Enrollment: 1150 (estimated)
• Ages: 18 Years to 110 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: radiation
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01875588 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the cognitive effects of HIV on individuals whose viral loads are controlled by medication. Researchers will enroll approximately 500 HIV-positive participants and 250 healthy volunteers to assess neuropsychological performance and brain health over a 20-year period. Participants will undergo various evaluations, including blood and urine tests, neuropsychological assessments, and brain imaging, with optional lumbar punctures for further analysis. The goal is to better understand the relationship between HIV and cognitive impairment, even in those with low viral loads.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with well-controlled HIV for at least one year and healthy volunteers of the same age.

Not a fit: Patients with uncontrolled HIV or those unable to commit to long-term participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of cognitive issues in HIV-positive individuals.

How similar studies have performed: While there have been studies on HIV-related cognitive impairment, this long-term observational approach is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

All Participants (HIV-infected and HIV-negative Controls):

While different individual HIV neurocognitive studies have specific selection criteria, especially related to HIV viral load and antiretroviral therapy, inclusion criteria for this overarching protocol will be flexible in order to identify the broadest base of potential enrollees possible.

1. 18 years of age and older.
2. Ability to sign informed consent by the participant.
3. At least seventh grade educational level and ability to speak, read, and understand English. Education level will be assessed by participant self-report. Because many of the neuropsychological subtests were validated using United States norms, participants must be native English speakers or if foreign-born, demonstrate ability to understand the English language at the time of protocol consent and neuropsychological testing.
4. Consent to store blood and tissue.
5. Willing to participate in this study for up to 20 years.

HIV-infected Only:

1. HIV-1 infection, as documented by OraQuick rapid test using venipuncture whole blood, or fingerstick whole blood; or with HIV-1/HIV-2 Multispot rapid test and Western Blot as determined by NIH Clinical Pathology Laboratory or Leidos Biomedical Research. Monitoring Laboratory.
2. Outside primary medical doctor who provides care.
3. Plasma HIV-RNA \<50 copies/mm3 or BLD for greater than one year. Participants who experience transitory episodes of an HIV viral load \> 50 copies/mm3 preceded and followed by plasma viremia \< 50 copies/mm3 may be included.
4. At least one year of continuous ART.

HIV-negative Controls Only:

1.HIV-antibody negative but can be taking pre-exposure prophylaxis (PrEP).

EXCLUSION CRITERIA:

1. Illness or other condition that, in the opinion of the PI, may interfere with study participation at the time of enrollment, including, but not limited to those listed below:

   1. CNS infections: this includes but is not limited to Varicella zoster virus (VZV) encephalitis, CNS lymphoma and toxoplasmosis. Participants who have recovered from effectively treated CNS infections may be considered once they resume baseline daily activities.
   2. Non-CNS opportunistic infections: Participants who recovered from or are completing treatment for non-CNS opportunistic infections (Ois) (e.g., Pneumocystis pneumonia, Candida esophagitis, or pulmonary TB) can be enrolled if they have returned to self-reported baseline activity and functional level.
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, untreated sleep apnea with day-time sleepiness, or seizure disorders. Participants with a history of seizure disorder with no seizure activity that are on a stable, non-sedating anti-seizure regimen for \>6 months may be enrolled.
3. Concurrent severe, unstable psychiatric illness that, in the opinion of the investigators, may interfere with study participation and/or data interpretation. Participants on psychotropic anxiolytic, attention deficit-hyperactivity disorder (ADHD), and other psychiatric medications may be included if clinically stable for 6 months.
4. Concurrent substance abuse that, in the opinion of the investigators may interfere with study participation and/or data interpretation. Active substance abuse includes illegal drug use and/or excessive narcotic or alcohol use as determined by the investigator. Urine drug screen will be performed on all participants. Use of nicotine containing products will not be an exclusion criterion.
5. 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), implanted delivery pump, or shrapnel fragments. Participants requiring a low dose oral benzodiazepine for mild to moderate claustrophobia will be allowed to participate. Pregnancy testing will be performed in enrolled participants of childbearing potential 48 hours prior to any MRI.
6. Medications: narcotics, psychiatric, and anti-seizure medications will not be allowed except under certain conditions as noted above. Corticosteroids may be permitted for participants on stable short-term therapy without CNS disease (i.e. resolving Pneumocystis pneumonia). Participants must be willing not to take the following medications within 48 hours of neuropsychological testing: sedating antihistamines such as diphenhydramine, zolpidem and other drugs identified by the study team that are associated with altered alertness or impaired memory.
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.
8. Pregnant persons are excluded due to exposure to high magnetic fields There is also exposure to radiation from the lumbar puncture if done under fluoroscopy. Participants of childbearing potental must have a negative serum or urine pregnancy 48 hours prior to any radiation exposure.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Avindra Nath, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
• Study coordinator: Amanda M Wiebold

Conditions HIV Positive; Healthy Controls; Neuropyschological Testing; Thinking and Memory; Lumbar Drain/Puncture; Natural History