HIV PositiveNCT01875588
Thinking and Memory Problems in People With HIV
An observational study of HIV Positive, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: People with human immunodeficiency virus (HIV) can sometimes develop thinking and memory problems. These problems can vary widely, from few symptoms to severe problems with memory and concentration. It initially was thought that good HIV treatment could prevent almost all HIV-related memory problems. Read more about this study
- Who is it for?
- Ages 18 to 110 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Positive
- How many people
- 1,150 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2013to 22 Feb 2037
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Any person meeting eligibility criteria and has no exclusionary criteria will be considered for the study.@@@
Who may be able to join
- 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.
- 18 years of age and older.
- Ability to sign informed consent by the participant.
- 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.
- Consent to store blood and tissue.
Show all 14Show fewer
- Willing to participate in this study for up to 20 years.
- HIV-infected Only:
- 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.
- Outside primary medical doctor who provides care.
- 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.
- At least one year of continuous ART.
- HIV-negative Controls Only:
- 1.HIV-antibody negative but can be taking pre-exposure prophylaxis (PrEP).
Who cannot join
- 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:
- 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.
- 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.
- 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.
- 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.
- 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.
Show all 10Show fewer
- 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.
- 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: An Evaluation of HIV-associated Neurocognitive Disorders (HAND) in Virologically Controlled Patients
Background:
- People with human immunodeficiency virus (HIV) can sometimes develop thinking and memory problems. These problems can vary widely, from few symptoms to severe problems with memory and concentration. It initially was thought that good HIV treatment could prevent almost all HIV-related memory problems. However, even people with low HIV viral loads can have these problems. It may be caused by HIV affecting the brain and spinal fluid. It is not yet clear why HIV causes these problems and why they may be worse in some people than others. Researchers want to study people with HIV and healthy volunteers to see how HIV may affect people with only small amounts of the virus in their blood.
Read more
Objectives:
- To study thinking and memory problems in individuals with HIV that is otherwise controlled with medications.
Eligibility:
- Individuals between 18 of age or older whose HIV has been controlled with medications for at least 1 year.
- Healthy volunteers between 18 of age or older.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. A neurological test will also be given. Participants will have a baseline imaging study of the brain.
- Within 12 weeks of the first visit, participants will have a second visit. Additional blood samples will be drawn. Another brain imaging study will be performed.
- Within 8 weeks of the second visit, participants will have a third visit to collect more blood samples. They will also provide spinal fluid samples, either as a single visit or a longer procedure.
- After this visit, participants will return every 12 months for up to 10 years. Blood samples will be collected as needed at these visits. Thinking and memory tests and imaging studies may also be given as needed. Spinal fluid may be collected at one visit a year.
Read the detailed description
The natural history of neurocognitive impairment in human immunodeficiency virus (HIV)-infected individuals remains poorly understood. While the advent of highly active antiretroviral therapy (HAART) has led to a decreased incidence of the most severe form of HIV associated neurocognitive disorders (HAND), HIV-associated dementia, it does not appear to have impacted overall prevalence of HAND. Existing evidence suggests that the central nervous system (CNS) could be an important reservoir for HIV regardless of cumulative time on treatment. This 20 year multi-institute natural history protocol will identify approximately 500 HIV-infected individuals and 250 healthy volunteers for enrollment in multiple HAND studies at the National Institutes of Health (NIH). Participants will undergo a screening and evaluation assessment, which will include blood and urine collection, neuropsychological testing, Client Diagnostic Questionnaire (CDQ), and brain magnetic resonance imaging (MRI) with optional lumbar puncture and ophthalmology exam to repeat yearly for up to ten years.
The option to have a lumbar drain is only on the first visit and extended to HIV positive individuals only. Participants will have the option of doing a positron emission tomography/computed tomography (PET/CT) imaging if they have previously had a PET/CT scan under this study. Cerebrospinal fluid (CSF) markers of immune activation, chronic monocyte activation, cytomegalovirus/Epstein-Barr virus (CMV/EBV) infection/reactivation, and neuronal injury will be collected. In addition, HIV viral load and genotype, genetic susceptibility factors and CNS penetration-effectiveness score (CPE) and CSF levels of antiretroviral drugs may be assessed. A repository of cryopreserved biological samples will be developed and used for validation of candidate biomarkers in future studies. Collection and analysis of these data will not only enhance understanding of the CNS as a potential HIV reservoir in virally-controlled individuals but will further define the association among cortical thickness, biomarkers and neurocognitive function in an aging HIV-infected population.
- Conditions
- HIV Positive
- Keywords
- Healthy Controls, HIV Positive, Neuropyschological Testing, Thinking and Memory, Lumbar Drain/Puncture, Natural History
- Medical subject headings
- HIV Seropositivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| DOD | Participants that are from IDCRP | |
| HIV negative controls | Participants that do not have HIV infection | |
| HIV positive | Participants that have HIV infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize in detail the natural course of HAND in subjects with prolonged plasma HIV virologic suppression (<50 copies/mL).
The prevalence of neurocognitive impairment in this cohort will be high despite HIV plasma viremia below the limit of detection (BLD) in the blood as chronic activation may be mediating neuronal damage and result in cognitive impairment.
Measured: Annually
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2013 (estimated)
- Study start8 Jul 2013
- Primary completion22 Feb 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV PositiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Avindra Nath, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01875588
- Sponsor's protocol ID
- 130149
- Other IDs
- 13-N-0149
- Status last verified
- 22 Sep 2026
- First submitted
- 11 Jun 2013
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. doi: 10.1212/01.WNL.0000287431.88658.8b. Epub 2007 Oct 3.
PubMed 17914061McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.
PubMed 15579274Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002 Apr;8(2):136-42. doi: 10.1080/13550280290049615.
PubMed 11935465
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of HIV-associated Neurocognitive Disorders (HAND) in Virologically Controlled Patients
- ClinicalTrials.gov ID
- NCT01875588
- Acronym / sponsor ID
- 130149
- Conditions
- HIV Positive
- Keywords
- Healthy Controls, HIV Positive, Neuropyschological Testing, Thinking and Memory, Lumbar Drain/Puncture, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,150 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 8 Jul 2013 (actual)
- Primary completion
- 22 Feb 2037 (estimated)
- First posted
- 12 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- People with human immunodeficiency virus (HIV) can sometimes develop thinking and memory problems. These problems can vary widely, from few symptoms to severe problems with memory and concentration. It initially was thought that good HIV treatment could prevent almost all HIV-related memory problems. However, even people with low HIV viral loads can have these problems. It may be caused by HIV affecting the brain and spinal fluid. It is not yet clear why HIV causes these problems and why they may be worse in some people than others. Researchers want to study people with HIV and healthy volunteers to see how HIV may affect people with only small amounts of the virus in their blood.
Objectives:
- To study thinking and memory problems in individuals with HIV that is otherwise controlled with medications.
Eligibility:
- Individuals between 18 of age or older whose HIV has been controlled with medications for at least 1 year.
- Healthy volunteers between 18 of age or older.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. A neurological test will also be given. Participants will have a baseline imaging study of the brain.
- Within 12 weeks of the first visit, participants will have a second visit. Additional blood samples will be drawn. Another brain imaging study will be performed.
- Within 8 weeks of the second visit, participants will have a third visit to collect more blood samples. They will also provide spinal fluid samples, either as a single visit or a longer procedure.
- After this visit, participants will return every 12 months for up to 10 years. Blood samples will be collected as needed at these visits. Thinking and memory tests and imaging studies may also be given as needed. Spinal fluid may be collected at one visit a year.
Detailed description
The natural history of neurocognitive impairment in human immunodeficiency virus (HIV)-infected individuals remains poorly understood. While the advent of highly active antiretroviral therapy (HAART) has led to a decreased incidence of the most severe form of HIV associated neurocognitive disorders (HAND), HIV-associated dementia, it does not appear to have impacted overall prevalence of HAND. Existing evidence suggests that the central nervous system (CNS) could be an important reservoir for HIV regardless of cumulative time on treatment. This 20 year multi-institute natural history protocol will identify approximately 500 HIV-infected individuals and 250 healthy volunteers for enrollment in multiple HAND studies at the National Institutes of Health (NIH). Participants will undergo a screening and evaluation assessment, which will include blood and urine collection, neuropsychological testing, Client Diagnostic Questionnaire (CDQ), and brain magnetic resonance imaging (MRI) with optional lumbar puncture and ophthalmology exam to repeat yearly for up to ten years.
The option to have a lumbar drain is only on the first visit and extended to HIV positive individuals only. Participants will have the option of doing a positron emission tomography/computed tomography (PET/CT) imaging if they have previously had a PET/CT scan under this study. Cerebrospinal fluid (CSF) markers of immune activation, chronic monocyte activation, cytomegalovirus/Epstein-Barr virus (CMV/EBV) infection/reactivation, and neuronal injury will be collected. In addition, HIV viral load and genotype, genetic susceptibility factors and CNS penetration-effectiveness score (CPE) and CSF levels of antiretroviral drugs may be assessed. A repository of cryopreserved biological samples will be developed and used for validation of candidate biomarkers in future studies. Collection and analysis of these data will not only enhance understanding of the CNS as a potential HIV reservoir in virally-controlled individuals but will further define the association among cortical thickness, biomarkers and neurocognitive function in an aging HIV-infected population.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DOD | – | –Participants that are from IDCRP |
| HIV negative controls | – | –Participants that do not have HIV infection |
| HIV positive | – | –Participants that have HIV infection |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Any person meeting eligibility criteria and has no exclusionary criteria will be considered for the study.@@@
Key inclusion criteria (14 listed)
- 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.
- 18 years of age and older.
- Ability to sign informed consent by the participant.
- 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.
- Consent to store blood and tissue.
Key exclusion criteria (10 listed)
- 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:
- 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.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To characterize in detail the natural course of HAND in subjects with prolonged plasma HIV virologic suppression (<50 copies/mL).
Time frame: Annually
The prevalence of neurocognitive impairment in this cohort will be high despite HIV plasma viremia below the limit of detection (BLD) in the blood as chronic activation may be mediating neuronal damage and result in cognitive impairment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Background: PubMed 17914061Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. doi: 10.1212/01.WNL.0000287431.88658.8b. Epub 2007 Oct 3.
- Background: PubMed 15579274McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.
- Background: PubMed 11935465Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002 Apr;8(2):136-42. doi: 10.1080/13550280290049615.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for HIV Positive
Recruiting
Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment to Physician-Led RR-TB Treatment
Drug Resistant Tuberculosis
Recruiting
Feasibility Study Comparing Use of One Or Two Probes for Thermal Ablation Among Screen Positive Women Living With HIV in C1001P-CS2 Kenya
HIV (Human Immunodeficiency Virus), HPV
Recruiting
Feasibility Study Comparing One vs Two Probes for Thermal Ablation Among Cervical Cancer Screen Positive WLWH in C1001P-CS9 South Africa
HIV (Human Immunodeficiency Virus), HPV
RecruitingPhase 2/3
Bedaquiline Roll-out Evidence in Contacts and People Living With HIV to Prevent TB
Tuberculosis, Latent
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Avindra Nath, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Positive, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amanda M Wiebold ((301) 538-9531, amanda.wiebold@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize in detail the natural course of HAND in subjects with prolonged plasma HIV virologic suppression (<50 copies/mL). (time frame: Annually). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01875588, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.