Lymphocyte Infusions for the Treatment of HIV-Infected Patients Failing Anti-HIV Therapy
Some HIV-infected individuals have a white blood cell marker known as HLA-B*57 that appears to help control the progress of the disease; however, not all who have the HLA-B*57 marker are able to control the infection. This study will examine the effects of giving white blood cells with HLA-B*57 from an individual who controls HIV infection to an individual who cannot control HIV infection, as a form of HIV treatment. All candidates will be screened with a medical history, physical examination, and blood and urine tests.
Both donor and recipient volunteers must be HIV-positive individuals 18 years of age or older who have the HLA-B*57 marker and are receiving care. Donor candidates must have positive HIV antibody tests for at least seven years with a recent CD4 cell count greater than 400 cells/mm?, HIV viral load less than 50 copies/mL, and no previous HIV viral load greater than 1,000 copies/mL. Recipient candidates must have positive HIV antibody tests with a recent CD4 cell count less than 400 cells/mm? and HIV viral load greater than 10,000 copies/mL, and must have failed at least two prior combination antiretroviral regimes and are willing to receive or resume combination antiretroviral therapy. Donor volunteers will be excluded if they have taken certain antiretrovirals drugs, have a medical history of cancer or of other blood-borne illnesses, or have other medical conditions that might interfere with the study. Recipient volunteers will be excluded if they have a medical history of malignant cancer or other medical conditions that might possibly interfere with the study.
Donors will undergo apheresis to separate white blood cells from circulating blood before the red blood cells and plasma are returned to the bloodstream. The procedure will take up to five hours, and donors will be required to return for additional tests. Donors may be asked to return for further white blood cell donations, a maximum of six procedures per year.
Recipients will undergo apheresis to obtain stem cells for possible use in the study, and will be admitted to an NIH Clinical Center inpatient unit to receive an infusion of white blood cells and undergo a series of blood tests both before and after the infusion. The infusion process will take two hours. After being discharged, recipients will be asked to return to the Clinical Center for monitoring and follow-up tests, and may receive further infusions....
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Immunologic and Virologic Response in HIV Infected Progressors After Infusion of Lymphocytes From HIV Infected "Elite" Long-Term Non-Progressors|
- Safety, survival of transferred cells.
- Changes in immune and viral parameters (CD4, Plasma HIV levels)
|Study Start Date:||November 2007|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Improvements in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatments in the United States have made the disease in many cases a chronic illness. However, many individuals have failed multiple lines of standard therapy, and thus, development of new modes of salvage treatment is crucial. Restriction of viral replication, mediated by CD8+ cells, appears to play an important role in control of HIV replication. A subset of individuals, many of whom possess human leukocyte antigen (HLA) B*57 exhibit restriction of HIV type 1 viral replication to less than 50 copies/mL, presumably by a mechanism that is CD8+ T-cell mediated, and become elite long-term non-progressors (LTNP), who have no evidence of progressive immunodeficiency and no development of opportunistic complications during many years of follow-up. Other individuals, including those with HLA-B*57 show no evidence of control of HIV replication, and without antiretroviral therapy will develop progressive immunodeficiency and HIV-related opportunistic complications. In this exploratory study, we are investigating a novel cell transfer strategy: up to 3 patients with HIV infection have failed at least 2 standard regimens of antiretroviral therapy, have a CD4+ count under 200 cells/mm (3), and a plasma HIV viral load of greater than 10,000 copies/mL, will be administered 10 (10) peripheral blood mononuclear cells obtained by lymphapheresis from an "elite" LTNP matched to the recipient on at least one HLA-B allele. Up to 70 patients may be enrolled for screening to identify 3 donors and 3 recipients. Up to 3 infusions may be administered per patient, with each infusion occurring no more frequently than every 3 months. The primary endpoints will be the safety of the infusions and the survival of donor cells in the recipient. Changes in the recipient s CD4+ and CD8+ cell number, other immune parameters, and plasma HIV viral load will also be monitored closely for evidence of anti-HIV activity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00559416
|Contact: Cheryl L. Chairez||(301) email@example.com|
|Contact: Joseph A Kovacs, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Joseph A Kovacs, M.D.||National Institutes of Health Clinical Center (CC)|