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

NCT02147405 | Recruiting

• 2 other identifiers: 14012414-I-0124
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune Reconstitution Inflammatory Syndrome

Keywords

FDG PET/CT Scan; Lymph Node Biopsy; Apheresis; Natural History

Outcome Measures

Primary Outcomes (3)

• Correlate LN inflammation (by FDG-PET)

  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

  Pathogenesis studies to evaluate role of myeloid cells in periphery and LN in IRIS

  After completion of enrollment of all participants.

• FDG-PET scans

  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.

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

random sample of participants.

You may qualify if:

• Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.
• 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
• Documented CD4+ cell count less than or equal to 100 cells/mm(3) within the past 8 weeks.
• 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
• Men or women age greater than or equal to 18 years.
• Ability and willingness of subject (or legal guardian/representative) to understand study requirements and give informed consent.
• Willingness to allow storage of blood or tissue samples for future research
• Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, optional FDG-PET/CT and lymph node biopsy\*)
• Willingness to have genetic testing
• Participants should have a primary care physician or will need to agree to have one established by 24 weeks on study.
• In the event of an estimated reversible inability to consent, patients may enroll via a legally authorized representative (DPA) if they have the ability to assign a DPA. For these participants, baseline lymph node biopsy will not be performed however the week 4-8 lymph node biopsy may be performed if the participant regains the capacity to consent prior to that time. If a subject permanently loses the ability to consent during participation, they will be withdrawn from the study.
• Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.
• Meet criteria suspicious for IRIS (Must meet 4/5 following criteria):
• I. Initiation (reintroduction or change) in antiretroviral therapy/regimen
• II. Evidence of:

You may not qualify if:

• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Inadequate venous access for phlebotomy and apheresis procedures as assessed by the study team.
• Women who are breastfeeding.
• 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.
• An inability to consent that is estimated by the study team to be irreversible.
• History of significant medical non-adherence which would, in the opinion of the investigator, interfere with study participation.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (7)

• Naidoo K, Yende-Zuma N, Padayatchi N, Naidoo K, Jithoo N, Nair G, Bamber S, Gengiah S, El-Sadr WM, Friedland G, Abdool Karim S. The immune reconstitution inflammatory syndrome after antiretroviral therapy initiation in patients with tuberculosis: findings from the SAPiT trial. Ann Intern Med. 2012 Sep 4;157(5):313-24. doi: 10.7326/0003-4819-157-5-201209040-00004.

  PMID: 22944873 BACKGROUND

• Barber DL, Andrade BB, Sereti I, Sher A. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol. 2012 Jan 9;10(2):150-6. doi: 10.1038/nrmicro2712.

  PMID: 22230950 BACKGROUND

• Sereti I, Rodger AJ, French MA. Biomarkers in immune reconstitution inflammatory syndrome: signals from pathogenesis. Curr Opin HIV AIDS. 2010 Nov;5(6):504-10. doi: 10.1097/COH.0b013e32833ed774.

  PMID: 20966640 BACKGROUND

• Lage SL, Ramaswami R, Rocco JM, Rupert A, Davis DA, Lurain K, Manion M, Whitby D, Yarchoan R, Sereti I. Inflammasome activation in patients with Kaposi sarcoma herpesvirus-associated diseases. Blood. 2024 Oct 3;144(14):1496-1507. doi: 10.1182/blood.2024024144.

  PMID: 38941593 DERIVED

• Rocco JM, Laidlaw E, Galindo F, Anderson M, Sortino O, Kuriakose S, Lisco A, Manion M, Sereti I. Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes. J Infect Dis. 2023 Jul 14;228(2):111-115. doi: 10.1093/infdis/jiad059.

  PMID: 37040388 DERIVED

• Manion M, Dulanto Chiang A, Pei L, Wong CS, Khil P, Hammoud DA, Anderson M, Laidlaw E, Kuriakose S, Lisco A; NISC Comparative Sequencing Program; Zelazny AM, Dekker JP, Sereti I. Disseminated Mycobacterium marinum in Human Immunodeficiency Virus Unmasked by Immune Reconstitution Inflammatory Syndrome. J Infect Dis. 2021 Aug 2;224(3):453-457. doi: 10.1093/infdis/jiaa769.

  PMID: 33336253 DERIVED

• Hammoud DA, Boulougoura A, Papadakis GZ, Wang J, Dodd LE, Rupert A, Higgins J, Roby G, Metzger D, Laidlaw E, Mican JM, Pau A, Lage S, Wong CS, Lisco A, Manion M, Sheikh V, Millo C, Sereti I. Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune Reconstitution Inflammatory Syndrome. Clin Infect Dis. 2019 Jan 7;68(2):229-238. doi: 10.1093/cid/ciy454.

  PMID: 30215671 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Immune Reconstitution Inflammatory Syndrome

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Irini Sereti, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irini Sereti, M.D.

CONTACT

(301) 496-5533; isereti@niaid.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2014
• First Posted: May 26, 2014
• Study Start: May 30, 2014
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-02-18

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)