HIV Infections
Conditions
Keywords
Monocytes, Interferon-gamma, Recombinant, Injections, Subcutaneous, Immune System, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Blood Bactericidal Activity
Brief summary
To find out which of four doses of (recombinant) human interferon gamma (IFN-G) is most effective in stimulating the white blood cells (monocytes) to fight infection and to see if treatment with IFN-G can strengthen the ability of AIDS patients to control infections. This study will also determine how long after a single injection of IFN-G white blood cells remain stimulated. AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best.
Detailed description
AIDS is a disease that progressively destroys that aspect of the body's defense called the immune system. It is particularly harmful to a class of cells called helper T-lymphocytes. The specific opportunistic infections and malignancies associated with AIDS have been treated with therapies that are often poorly tolerated by the patients and are associated with dose-limiting toxicities. The principal focus of AIDS therapy research at present is to control the underlying retroviral infection and to restore immune function with recombinant lymphokines, adoptive immunotherapy, and/or lymphocyte transplants. These treatments include zidovudine (AZT), which has been shown to control the HIV infection, and IFN-G, a lymphokine which activates tumor-destroying and germ-killing functions. Studies are needed to find the dose by which IFN-G works best. Patients, who may participate in all three parts of the study, are maintained on a stable dose of AZT. In part A (optimal dose), five AIDS patients who have had an AIDS related opportunistic infection receive 4 once-weekly increasing doses of IFN-G. Monocyte antimicrobial activity is examined in test tube studies before and after each injection of IFN-G. In part B, five patients receive the optimal dose of IFN-G established in part A. Patients enrolled from part A have completed at least 2 weeks of part A before enrolling in part B. Antimicrobial activity is examined 1, 2, and 3 days after a single injection of the optimal dose of IFN-G (determined in part A). In part C (safety and tolerance of combined treatment of IFN-G and AZT), patients are treated with IFN-G for 4 weeks using the optimal dose and administration schedule derived from parts A and B.
Interventions
DRUGZidovudine
DRUGInterferon gamma-1b
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Concurrent Medication: Allowed: * Prophylactic antibiotics. * Tylenol (650 mg orally every 6 hours as needed for temperature \> 38.5 degrees C). * Meperidine (25 - 50 mg intravenously, once, for severe rigors if systolic blood pressure is \> 90 mmHg). Patients must meet criteria for AIDS classification (CDC) category IV C-1. * Patients must have had one or more prior opportunistic infections identified in surveillance definition of AIDS. Patients whose AIDS-defining illness is Kaposi's sarcoma are also eligible if they have previously had one of the secondary infectious diseases identified in category C-1. Prior Medication: Required: * Patients must have been receiving zidovudine (AZT) on a stable dosage regimen for at least 8 weeks immediately preceding entry into study.
Exclusion criteria
Co-existing Condition: Patients with the following are excluded: * Clinically significant cardiac (= or \> class II, New York Heart Association) or peripheral vascular disease that requires treatment. * Presence of an active opportunistic infection that requires treatment. * Hemorrhagic diathesis or active bleeding disorder. * Clinically apparent vascular disease. Concurrent Medication: Excluded: * Medications required for treatment of active cardiac disease. * Ongoing therapy with anticoagulants or thrombolytic agents. Patients with the following are excluded: * Clinically significant cardiac (= or \> class II, New York Heart Association) or peripheral vascular disease that requires treatment. * Presence of an active opportunistic infection that requires treatment. * Hemorrhagic diathesis or active bleeding disorder. * Clinically apparent vascular disease. Prior Medication: Excluded within 4 weeks of study entry: * Antiviral chemotherapy other than zidovudine. * Excluded within 12 weeks of study entry: * Immunosuppressive or cytotoxic therapy.
Countries
United States
Outcome results
None listed