Immune Reconstitution Syndrome in HIV-Infected Patients Taking Antiretroviral Therapy

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Feb 2, 2006

Keywords

ClinConnect 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 i...

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Eligibility criteria

• * INCLUSION CRITERIA:
• • 1. For the National Institutes of Health (NIH)/US site: HIV-1 infection, as documented by OraQuick rapid test using venipuncture whole blood, or fingerstick whole blood done at screening; or by reactive enzyme-linked immunosorbent assay (ELISA) and Western Blot as determined by NIH Clinical Pathology Laboratory or Leidos Biomedical Research, Inc. Monitoring Laboratory. HIV infection as determined by an outside Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory facility" will be accepted for enrollment and verified by a standard HIV-1 ELISA with Western Blot at NIH.
• • For Keny Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP CRC)/Kenya site: HIV-1 infection will initially be diagnosed based upon two, serial rapid HIV tests according to Kenya Ministry of Health (MOH) guidelines. Volunteers entering this study will have HIV infection confirmed by two serial rapid HIV test in accordance with Kenya MOH guidelines and testing algorithm followed by a confirmation with a Western Blot using FDA approved-kits. Samples from participants with discrepant results (between the results from other institution and KEMRI/WRP-CRC laboratory) and/or indeterminate/negative Western Blot will be subjected to a nucleic acid assay i.e. DNA or RNA PCR. For Thailand, HIV-1 screening and confirmatory testing will be based on 3, HIV tests according to the Thai Ministry of Public Health guidelines. The subjects will initially be tested with a chemiluminescent microparticle immunoassay (CMIA) method that detects both HIV antigen and antibody. Confirmatory testing of HIV reactive samples by two different antibody detection methods will follow. Positive results by all three methods confirm HIV diagnosis. Discrepancy between the tests will require a nucleic acid detection method to confirm HIV diagnosis.
• • 2. No previous treatment with potent combination anti-retroviral therapy (ART), defined as any protease inhibitor (PI)-based or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, or even triple nucleoside reverse transcriptase inhibitors (NRTI)-based regimen, consisting of at least three antiretroviral drugs (including a boosted PI with NNRTI combination). Patients with limited use of ART (less than 12 weeks duration) more than 24 weeks before screening will be eligible for study participation.
• • 3. Screening CD4+ cell count less than or equal to 100 cells/mm(3). \* Note: CD4 \< 100 cells/microL from an outside or the site s laboratory within 8 weeks prior to screening can be accepted as the screening value.
• • 4. Residence within the wider Washington D.C. area (approximately within a 120-mile radius from the NIH Bethesda campus) for the National Institutes of Health/US site and residents of the Kericho District Hospital catchment area, an approximate 93-mile (150 kilometers) radius, for the KEMRI/WRP CRC/Kenya site. Residence within the Bangkok Metropolitan area and nearby provinces are allowed to participate (approximately 120-mile radius from each of the clinical sites)
• • 5. Men and 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. Be willing to allow storage of blood or tissue samples for future research. (For Thailand: storage of blood or tissue samples is an optional procedure and therefore not a inclusion criteria)
• • 8. Be willing to have HLA testing. (For Thailand: HLA testing is an optional procedure and therefore not an inclusion criteria)
• • 9. For the NIH/US site: Participants should have a primary care physician or will need to agree to find one during the first 24-48 weeks on study. For the KEMRI/WRP/Kenya site: Participants must be enrolled in the Kericho District Hospital HIV Clinic. For the two Thailand clinical sites: participants must be enrolled in the HIV clinic at either of the sites.
• 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, diagnostic testing, and follow-up.