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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2026
  • participants needed
    300
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Send
Updated on 28 October 2022
See if I qualify

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.

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.

Details
Condition Immune Reconstitution Inflammatory Syndrome
Clinical Study IdentifierNCT02147405
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on28 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
IRIS ARM INCLUSION CRITERIA
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)
Initiation (reintroduction or change) in antiretroviral therapy/regimen
II. Evidence of
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
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
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
Men or women age greater than or equal to 18 years
Ability and willingness of subject 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
an optional FDG-PET/CT, and lymph node biopsy)
Willingness to have genetic testing
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

Exclusion Criteria

Active drug or alcohol use or dependence that, in the opinion of the investigator
Women who are breastfeeding
would interfere with adherence to study requirements
Pregnancy will be an exclusion criterion for study entry given the intense nature of
An inability to consent that is estimated by the study team to be irreversible
the protocol regarding blood draws, apheresis, biopsies and FDG-PET/CT imaging
Inadequate venous access for phlebotomy and apheresis procedures as assessed by the
study team
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
History of significant medical non-adherence which would, in the opinion of the
investigator, interfere with study participation
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name
Edit Delete

Added by • 

 • 

Private

Edit Delete

Reply by • • Private
Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note