the safety and effectiveness of injections of human recombinant interferon-gamma in patients with aids who have taken zidovudine

Conditions: HIV Infections

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.

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.

Eligibility criteria:
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.

Keywords: monocytes interferon-gamma, recombinant injections, subcutaneous immune system drug evaluation drug therapy, combination acquired immunodeficiency syndrome zidovudine blood bactericidal activity