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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

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:

<TAB><TAB>- review of medical history<TAB>

<TAB><TAB>- physical and eye exams

<TAB><TAB>- blood, urine, and tuberculosis (TB) tests

<TAB><TAB>- electrocardiogram (EKG)

<TAB><TAB>- chest x-ray

  • apheresis: a blood drawing procedure where blood is removed from a vein, white blood cells are separated and

    Detailed Summary:

    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). A ART Naive arm will enroll 100 patients who are ART-naive 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 20 participants who are ART-treated and meet criteria suspicious for IRIS (Appendix D), 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.


    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome:

    • Correlate LN inflammation (by FDG-PET) and degree of fibrosis as assessed by immunohistochemistry (IHC) with development of IRIS and degree of immune reconstitution after 1 year of ART. [ Time Frame: After completion of enrollment of all participants ]
    • Pathogenesis studies to evaluate role of myeloid cells in periphery and LN in IRIS. [ 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. [ Time Frame: After completion of enrollment of all participants ]


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: May 22, 2014
    Date Started: May 20, 2014
    Date Completion: December 1, 2019
    Last Updated: April 21, 2017
    Last Verified: March 16, 2017