Immune Reconstitution Syndrome in HIV-Infected Patients Taking Antiretroviral Therapy
|First Received Date ICMJE||February 3, 2006|
|Last Updated Date||March 14, 2014|
|Start Date ICMJE||January 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00286767 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Immune Reconstitution Syndrome in HIV-Infected Patients Taking Antiretroviral Therapy|
|Official Title ICMJE||A Cohort Observational Study Evaluating Predictors, Incidence and Immunopathogenesis of Immune Reconstitution Syndrome (IRIS) in HIV-1 Infected Patients With CD4 Count Less Than or Equal to 100 Cells/microL Who Are Initiating Antiretroviral Therapy|
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. They start taking anti-HIV medications, prescribed according to the current standard of care, as well as medications to treat other infections, and treatment of IRIS, if needed. The study lasts about 4 years. Patients return to the clinic at 2, 4, 8 and 12 weeks after the entry visit, then every 12 weeks (about every 3 months) until week 48 (the first year), and then every 16 weeks (about every 4 months) until the end of the study. At most visits, patients have a medical history, physical examination and blood and urine tests, including CD4+T cell count and HIV plasma viral load measurement. Apheresis is also done at weeks 24 and 48 and then once every 48 weeks. Intestinal and lymph node biopsies (optional) are also done at weeks 24 and 48. A syphilis test and PAP smear (for women) are done yearly. and plasma, cells and serum are stored at almost every visit for immunologic studies.
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 followed for at least two years. Total duration of the study will be approximately 8 years (including the optional extension phase in US).
SAMPLE SIZE: Approximately 600 patients will be enrolled, 200 in Kenya, 100 in Thailand and 300 in US. (enrollment is US will continue until approximately the other sites are full). Based on the incidence of IRIS in patients with low CD4 counts (approximately 20-40 percent), we anticipate strong power (approximately 90 percent) to identify baseline factors predictive of IRIS.
POPULATION: HIV-l-infected men and women, age greater than or equal to 18 years, antiretroviral therapy (ART)-naive with CD4+ T cell counts less than or equal to 100 cells/mm(3). Participants will be recruited and followed at three sites: the broader Washington DC, Kericho, Kenya and Bangkok, Thailand areas.
REGIMEN: Participants will be initiated on ART according to the clinical standard of care. If an OI or other AIDS defining illness is identified prior to or during screening or at any point during the study, they will also be treated according to standard of care.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||HIV Infections|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||600|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States, Kenya, Thailand|
|NCT Number ICMJE||NCT00286767|
|Other Study ID Numbers ICMJE||060086, 06-I-0086|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP