Investigating Immune Reconstitution Inflammatory Syndrome in People with HIV

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

This study is trying to understand what causes immune reconstitution inflammatory syndrome (IRIS) in adults with HIV by looking at two groups: those new to treatment and those already on treatment who have symptoms.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT02147405 on ClinicalTrials.gov

What this trial studies

This observational study aims to understand the causes and effects of immune reconstitution inflammatory syndrome (IRIS) in adults with HIV. Participants will be divided into two groups: those who are ART-naive with low CD4 counts and those already on ART showing symptoms of IRIS. The study will involve comprehensive screening, including blood tests, medical history reviews, and imaging, to identify predictors and mechanisms of IRIS. Participants will be followed for up to 96 weeks to monitor their health and response to treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with HIV and low CD4 counts who are about to start HIV medications or those already on treatment with symptoms related to IRIS.

Not a fit: Patients who are not HIV-positive or those with stable CD4 counts and no symptoms of IRIS may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management and prevention strategies for IRIS in HIV patients.

How similar studies have performed: While studies on IRIS have been conducted, this specific approach focusing on comprehensive screening and imaging is relatively novel.

Eligibility criteria

* 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 less than or equal to 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 greater than or equal to 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.

    * 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.

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):

   I. Initiation (reintroduction or change) in antiretroviral therapy/regimen

   II. Evidence of:
   1. an increase in CD4+ cell count defined as greater than or equal to 50cell/mm(3) or a greater than or equal to 2 fold rise in CD4+ cell count, and/or
   2. decrease in the HIV-1 viral load of greater than or equal to 0.5 log10

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

   IV. Theses 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.

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

   \*Criteria IV or V 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 greater than or equal to 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.

   * In the event of an estimated reversible inability to consent, patients may enroll using a legally authorized representative (DPA) if they have the ability to assign a DPA. lymph node biopsy will not be performed in these occasions. If a subject permanently loses the ability to consent during participation, they will be withdrawn from the study.

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.

Where this trial is running

Bethesda, Maryland

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

Study contacts

• Principal investigator: Irini Sereti, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Irini Sereti, M.D.

Conditions Immune Reconstitution Inflammatory Syndrome; FDG PET/CT Scan; Lymph Node Biopsy; Apheresis; Natural History