Clinical Trial: Immune Reconstitution Syndrome in HIV-Infected Patients Taking Antiretroviral Therapy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: A Cohort Observational Study Evaluating Predictors, Incidence and Immunopathogenesis of Immune Reconstitution Syndrome (IRIS) in HIV-1 Infected Patients With CD4 Count Les

Brief Summary:

This study will investigate what factors may lead to the development of immune reconstitution syndrome (IRIS) in HIV-infected patients and what the outcome is after IRIS. It will also seek to better define and describe the syndrome. IRIS is a condition that can occur in HIV-infected people following the start of antiretroviral therapy. The sudden improvement of immune function with this therapy can cause an unexpected worsening of diseases the patient already has, such as tuberculosis or fungal infections, and development of fever, enlarged lymph nodes or other complications, or even uncover a previously silent disease.

HIV-infected people who are at least 18 years old, whose CD4+T cell count is 100 cells per microliter or less, and who have not previously been treated with combination antiretroviral therapy or have taken the drugs for less than 3 months and more than 6 months before screening for this study may be eligible to participate. Candindates must also live within the wider DC area so that acute problems after therapy initiation will be evaluated at NIH. Candidates are evaluated before starting therapy with a medical history and physical examination, blood and urine tests, electrocardiogram, chest x-ray and CT scan of the chest, tuberculin skin testing, apheresis, and possibly an intestinal (gut) and lymph node biopsy (surgical removal of a small piece of tissue for microscopic examination). For apheresis, blood is collected through a needle in an arm vein and spun in a machine that separates the blood components. The white blood cells and plasma are removed, and the red cells and platelets are returned through the same needle or through a needle in a vein in the other arm.

Participants have a complete history and physical examination and additional blood tests, including genetic studies, upon entering the study.

Detailed Summary:

A cohort observational study evaluating the predictors, incidence, clinical presentation and immunopathogenesis of Immune Reconstitution Syndrome (IRIS) in human immunodeficiency virus (HIV-1) infected patients with CD4 Count less than or equal to 100 cells/microL who are initiating antiretroviral therapy.

Immune reconstitution syndrome (IRIS) is a clinical syndrome that has been described in HIV infected patients after initiation of highly active anti-retroviral therapy (HAART), and is characterized by paradoxical acute worsening of an underlying opportunistic infection or AIDS-defining illness. There is no widely accepted syndromic definition, the pathogenesis of the syndrome is unclear and there is no specific therapy. The syndrome is more common in patients with low CD4+ T cell counts (less than 50 cells/microL) and in those with certain underlying infections (e.g. mycobacterial or cryptococcal infection) and is typically observed when there is evidence of response to HAART and while patients are still at risk for other opportunistic infections (OIs) or AIDS defining illnesses (e.g. pneumocystis jirovecii pneumonia or cytomegalovirus [CMV] retinitis). The incidence of IRIS varies depending on the studied population and is very frequent in developing countries creating significant diagnostic and therapeutic challenges as well as utilization of limited health resources.

DESIGN: International observational cohort study. Participants will be evaluated at baseline and followed according to the protocol follow up schedule after initiation of antiretroviral therapy for a total of two years. Acute symptoms that may be representing manifestations of IRIS will also be evaluated at additional acute care visits if necessary.

DURATION: Enrollment is ongoing. Each volunteer will be f
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • To identify baseline predictors of IRIS within 6 months of HAART initiation prospectively in a group of HIV-1 infected patients with advanced disease who are starting antiretroviral therapy. [ Time Frame: During the data analysis phase at the end of the study ]
  • To evaluate the immunopathogenesis of IRIS with the goal to identify more appropriate targets for future therapeutic interventions. [ Time Frame: During the data analysis phase at the end of the study ]


Original Primary Outcome:

Current Secondary Outcome:

  • Evaluate the baseline clinical and immunological characteristics ofindividuals who develop IRIS and compare them with those who do not. [ Time Frame: During the data analysis phase at the end of the study ]
  • To study the incidence and clinical manifestations of IRIS prospectively in a group of HIV-1 infected patients with advanced disease who are initiating antiretroviral therapy. [ Time Frame: During the data analysis phase at the end of the study ]
  • To evaluate the impact of IRIS on the risk of subsequent death (attributable mortality). [ Time Frame: During the data analysis phase at the end of the study ]


Original Secondary Outcome:

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

Dates:
Date Received: February 3, 2006
Date Started: January 30, 2006
Date Completion:
Last Updated: April 21, 2017
Last Verified: December 7, 2016