PET Imaging and Lymph Node Assessment of IRIS in People With AIDS

June 4, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

PET Imaging and Lymph Node Assessment of IRIS in Persons With AIDS

Background:

- Sometimes people with HIV, the virus that causes AIDS, can have new or worsening symptoms soon after starting HIV medications. Often these symptoms are caused by immune reconstitution inflammatory syndrome (IRIS). Researchers want to study why and how people develop IRIS and how best to prevent and treat it.

Objectives:

- To learn the causes and effects of IRIS, and how to best manage it.

Eligibility:

- Adults 18 and older with HIV and low CD4 counts,, about to start HIV medicines; or those already taking HIV medicines with symptoms thought to be related to IRIS.

Design:

  • Participants not on ART will have screening blood tests for CD4 count, HIV viral load and genetic testing.
  • After the screening blood tests and before starting HIV medicines., participants will return for more than 1 visit for the following:
  • review of medical history<TAB>
  • physical and eye exams
  • blood, urine, and tuberculosis (TB) tests
  • electrocardiogram (EKG)
  • chest x-ray
  • apheresis: a blood drawing procedure where blood is removed from a vein, white blood cells are separated and collected, and the rest of the blood is returned to the person using another vein
  • - PET scan - a procedure where a small amount of radioactive material is injected in a vein. The participant then lies on a table that slides into a scanner which takes images of the body.
  • lymph node biopsy
  • stool collection by swab
  • After completion of the above, HIV medicines will be started.
  • Follow-up visits will be at 2, 4, 8, and 12 weeks after starting ART, then every 12 weeks. Some of the tests above may be repeated.
  • Participants already on HIV medicines who may have IRIS will be screened over a 4 week time period to see if they really are experiencing IRIS. The screening process will include all of the items listed above. Follow-up visits will be at Weeks, 4, 8, 12 and then every 12 weeks.
  • The study will last 1 year for both groups but may be extended to 2 years (3 additional appointments) for some participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Immune reconstitution inflammatory syndrome (IRIS) in HIV infection represents a paradoxical, frequently inflammatory, immune response after initiation of antiretroviral (ART) therapy. The immunopathogenesis of IRIS remains elusive partially due to a lack of tissue sampling and a lack of detailed screening, including imaging, for subclinical opportunistic infections in many studies. Most pathogenesis studies to date have been performed in peripheral blood with a few notable exceptions of cryptococcal IRIS studies in which cerebrospinal fluid (CSF) samples were obtained and evaluated.

This is a 2-arm natural history study intended to evaluate the incidence, predictors and pathogenic mechanisms of IRIS in HIV-1 infected adults (age >18 years). An ART naive arm will enroll 140 patients who are ART-na(SqrRoot) ve with CD4+ T cell counts <100 cells/mm^3. These participants will initiate ART according to the clinical standard of care. Any opportunistic infections (OIs) or AIDS-defining illnesses identified prior to, during screening or at any point during the study, will also be treated according to standard of care. The IRIS arm will enroll 60 participants who are ART-treated and meet criteria suspicious for IRIS, with any CD4+ T cell count. The ART naive arm will be followed for 48 weeks, with an optional extension up to week 96. The IRIS arm will be followed for 48 weeks after enrollment if the IRIS event is confirmed, also with an optional extension up to week 96. In both arms, subjects must have adequate venous access and will undergo collection of whole blood by phlebotomy, leukapheresis, lymph node biopsy, and fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) at designated study visits.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

random sample of participants.

Description

  • ELIGIBILITY CRITERIA:

ART NAIVE ARM INCLUSION CRITERIA:

  1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.
  2. No recent (within the past two years) treatment with combination anti-retroviral therapy (ART). Patients with limited (no more than 2-3 weeks) recent use of potent combination ART may be eligible for study participation if, the opinion of the investigator, the ART usage will not impact the scientific validity of the protocol
  3. Documented CD4+ cell count <=100 cells/mm^3 within the past 8 weeks.
  4. Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus) and plans to stay in the area for 48 weeks
  5. Men or women age >=18 years.
  6. Ability and willingness of subject (or legal guardian/representative) to understand study requirements and give informed consent*.
  7. Willingness to allow storage of blood or tissue samples for future research
  8. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, optional FDG-PET/CT and lymph node biopsy)
  9. Willingness to have genetic testing

  10. Participants should have a primary care physician or will need to agree to have one established by 24 weeks on study.

    • Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time.

IRIS ARM INCLUSION CRITERIA:

  1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.

  2. Meet criteria suspicious for IRIS (Must meet 4/5 following criteria):

    1. Initiation (reintroduction or change) in antiretroviral therapy/regimen
    2. Evidence of:

    i. an increase in CD4+ cell count defined as >= 50cell/mm^3 or a >= 2 fold rise in CD4+ cell count, and/or

    ii. decrease in the HIV-1 viral load of >=0.5 log10

    c. Symptoms and/or signs consistent with an infectious/inflammatory condition.

    d. These symptoms and/or signs cannot be explained by a newly acquired infection, the expected clinical course of a previously recognized infectious agent, or the side effects of antiretroviral therapy itself.

    e. The infectious/inflammatory condition must be attributable to a specific pathogen or condition.

    Criteria d or e may not be met for suspected IRIS definition.

  3. Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus) **Participants from outside of the 100 mile radius may be enrolled on a case by case basis to diagnose or manage IRIS.
  4. Men or women age >=18 years.
  5. Ability and willingness of subject to understand study requirements and give informed consent*.
  6. Willingness to allow storage of blood or tissue samples for future research
  7. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, an optional FDG-PET/CT, and lymph node biopsy)
  8. Willingness to have genetic testing

  9. Participants should have a primary care physician who will initiate the referral.

    • Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time.

SUBJECT EXCLUSION CRITERIA:

  1. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
  2. Pregnancy will be an exclusion criterion for study entry given the intense nature of the protocol regarding blood draws, apheresis, biopsies and FDG-PET/CT imaging.
  3. Inadequate venous access for phlebotomy and apheresis procedures as assessed by the study team.
  4. Women who are breastfeeding.
  5. A life-threatening underlying illness that according to the study team requires immediate intervention such as PML requiring initiation of ARVs or lymphomas requiring chemotherapy initiation.
  6. An inability to consent that is estimated by the study team to be irreversible.
  7. History of significant medical non-adherence which would, in the opinion of the investigator, interfere with study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
ARV naive
Patients that have not started or have ever been on ARV therapy.
IRIS
Patients that are on medication but are possibly experiencing an IRIS event.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Correlate LN inflammation (by FDG-PET)
Time Frame: After completion of enrollment of all participants.
Correlate LN inflammation (by FDG-PET) and degree of fibrosis as assessed by immunohistochemistry (IHC) with development of IRIS and degree if immune reconstitution after 1 year of ART
After completion of enrollment of all participants.
Pathogenesis studies
Time Frame: After completion of enrollment of all participants.
Pathogenesis studies to evaluate role of myeloid cells in periphery and LN in IRIS
After completion of enrollment of all participants.
FDG-PET scans
Time Frame: After completion of enrollment of all participants.
FDG-PET measurements and correlations with viremia, biomarkers, OI, immune recovery of B cells and Tfh cells with ART
After completion of enrollment of all participants.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Irini Sereti, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 30, 2014

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 26, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 22, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 140124
  • 14-I-0124

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to make IPD available at this time.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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