Protocol Number: 06-I-0086

Title:

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/micro L Who Are Initiating Antiretroviral Therapy

Number:

06-I-0086

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. 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.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

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 SAIC-Frederick 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 ELISA and Western Blot tests consistent with the KEMRI/WRP laboratory algorithm.

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) obtained within 28 days prior to ART visit.

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 kilometers0 radius, for the KEMRI/WRP CRC/Kenya site.

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.

8. Be willing to have HLA testing.

9. Participants must have primary care physician or will need to agree to find one during the first 24 weeks on study. For the KEMRI/WRP/Kenya site: Participants must be enrolled in the Kericho District Hospital HIV Clinic

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.

Special Instructions:

Currently Not Provided

Keywords:

Opportunistic Infections

Immune Restoration Disease

Mycobacterial Infections

Recruitment Keyword(s):

HIV-1 Infection

HIV

ART Naive

Condition(s):

HIV Infections

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS. 2004 Aug 20;18(12):1615-27. Review.

Shelburne SA 3rd, Hamill RJ. The immune reconstitution inflammatory syndrome. AIDS Rev. 2003 Apr-Jun;5(2):67-79. Review.

Stoll M, Schmidt RE. Immune Restoration Inflammatory Syndromes: The Dark Side of Successful Antiretroviral Treatment. Curr Infect Dis Rep. 2003 Jun;5(3):266-276.

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