A first-of-its-kind pilot study sponsored by the National Institute of Allergy and Infectious Disease (NIAID) has begun to evaluate the treatment of HIV-infected persons with large numbers of their own HIV-fighting immune cells grown in the laboratory. HIV is the virus that causes AIDS.
The study will assess the safety and feasibility of infusing HIV-infected persons with cytotoxic "killer" T cells that have been taken from their blood, selected for their ability to kill HIV-infected cells and cultured in the laboratory. A similar approach has been used for patients with cancer, but the NIAID trial is the first to administer HIV-specific, laboratory-selected cytotoxic T cells to patients with HIV infection.
"Cytotoxic T cells, sometimes called killer T cell, are important weapons in the body's immune defense against viruses, including HIV, that have infected cells, "explains Anthony S. Fauci, M.D., NIAID Director. "Previous studies suggest that patients who progress to the late stages of HIV infection may lack functional cytotoxic T cells."
Between 15 and 24 patients will take part in the study at the New England Medical Center in Boston, Mass., a site of the Division of AIDS Treatment Research Initiative (DATRI). DATRI is one of NIAID's three AIDS clinical trials networks. The other two NIAID networks are the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).
The study physicians, under the direction of principal investigator Judy Lieberman, M.D., Ph.D., a physician in the Hematology/Oncology Department of the New England Medical Center and assistant professor of medicine at Tufts University School of Medicine, will enroll patients with CD4+ T cell counts in the range of 100 to 400 per cubic millimeter of blood. CD4+ T cells are the crucial immune system cells depleted during HIV infection. Patients in the study will continue to take any prescribed anti-HIV medications and preventive drugs for Pneumocystis carinii pneumonia, a common HIV-related lung infection.
After study doctors evaluate participants' health with physical examinations and laboratory tests, the investigators will test blood samples from eligible patients to determine whether their cytotoxic T cells can kill HIV-infected cells. Selected cells will then be grown in the quantities required for infusion. At a subsequent visit to the hospital, patients will be admitted for the night and receive intravenous infusions of 1 billion, 5 billion or 25 billion cytotoxic T cells derived from their own blood. Study investigators will follow the patients for 24 weeks to determine the effects of the treatment on their infections and to monitor any side effects.
"This is a highly complex and labor-intensive study, " says Daniel F. Hoth, M.D., director of NIAID's of AIDS. " As a result, it likely will not be possible to enroll more than one patient per month. Two years may be required to complete the study, but this study design should provide us with the most definite data to use to assess this therapy."
In previous laboratory studies, the blood from approximately two-thirds of HIV-infected patients have shown the ability to kill HIV-infected cells. The investigators anticipate screening 40 to 64 patients to attain the desired number of eligible patients.
NIAID established the DATRI network in 1991 to rapidly conduct clinical trials, particularly with new therapies and novel treatment approaches, for those with HIV disease. Therapies that show promise in DATRI studies may be considered for larger scale clinical trials in the ACTG or the CPCRA.
"Innovative approaches to treatment, such as that being evaluated in this latest DATRI study, are crucial to our goal of making HIV a manageable disease," says Dr. Hoth. "Currently only AZT, ddI and ddC in combination with AZT have been approved for treating HIV infection. These therapies can slow the progression of HIV disease but have not been shown to control it."
NIAID, a component of the National Institutes of Health, supports research on allergy, immunology and infectious diseases. NIH is an agency of the U.S. Public Health Service, Department of Health and Human Services.
For enrollment information, site location and eligibility requirements for all NIAID clinical trials, please call 1-800- TRIALS-A, Monday through Friday 9 a.m. to 7 p.m., EST.