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Drugs used to treat bacterial infection of the blood and certain types of blood and solid tissue cancers are now being considered for treatment of infection with human immunodeficiency virus type I (HIV-I), which causes AIDS. The combined use of agents with different mechanisms of action, side effects, or patterns of resistance may be effective in eliminating HIV-I infection. If the antiviral actions of drugs are synergistic, or greater when combined than when used alone, it may be possible to administer lower doses of each drug. In addition, optimal doses of drugs with similar mechanisms of actions, but different toxic effects can be used in combined regimens. Viral resistance to a drug may develop less readily with combined regimens than with single drug therapy. The antiviral agent zidovudine interferes with the production of genetic material of HIV-I, whereas interferon-alpha (IFN-alpha) prevents the production of the virus. Zidovudine and IFN-alpha were reported to be synergistic, but cause neutropenia, a severe decrease in the number of neutrophils (a type of white blood cell). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor that can be produced artificially in large amounts using recombinant technology. GM-CSF was shown to improve neutropenia in patients with cancer, AIDS, or bone marrow suppression. The side effects of GM-CSF are mild, related to dosage, and include fever and bone pain. The effectiveness of GM-CSF in treating neutropenia associated with combined zidovudine and IFN-alpha treatment was assessed in 24 HIV-I-infected patients. The blood levels of p24 antigen, a measure of HIV-I infection, decreased by more than 70 percent in five patients with this antigen. Combined treatment with zidovudine, IFN-alpha, and GM-CSF was associated with lymphokine-like side effects: loss of appetite, weight loss, fatigue, and a decrease in red blood cells. However, GM-CSF improved neutropenia without reducing the antiviral action of zidovudine and IFN-alpha. (Consumer Summary produced by Reliance Medical Information, Inc.)

In the presence of a foreign particle, also known as an antigen, immune B cells produce antibodies that specifically bind and destroy the foreign particle. Another type of immune cell, the T helper cell, enhances the production of antibodies by B cells; T suppressor cells decrease the production of antibodies by B cells. Infection by the human immunodeficiency virus (HIV) is associated with a variety of abnormalities of the immune system, the most common of which is a decrease in the number of CD4 helper/inducer T lymphocytes. The destruction of CD4 cells by HIV results in a decrease in antibody production and a reduced ability to fight infection. HIV infection is also associated with abnormalities in the number and activity of CD8 suppressor/ cytotoxic T lymphocytes; defects in ability to recognize an antigen; abnormalities in the activation of B cells to produce antibodies; and reduced ability to kill cells. However, the CD4 cell defect is the most important immune abnormality in the pathogenesis of HIV disease. A better understanding of the relation between CD4 cell defects and the development of clinical symptoms may help in the treatment of HIV infection. (Consumer Summary produced by Reliance Medical Information, Inc.)

Kaposi's sarcoma is the formation of multiple areas of cell overgrowth on the skin and other body sites; these areas develop into sarcomas or cancerous growths arising from connective tissue such as bone or muscle. The disease is thought to result from the weakened immune function associated with acquired immunodeficiency syndrome (AIDS). The effectiveness and toxicity of the combined drug regimen of zidovudine and interferon-alpha was assessed in 39 patients with Kaposi's sarcoma and AIDS. Interferon, a protein produced after exposure of cells to viruses or foreign nucleic acids, is involved in immune and antitumor reactions. The results show that the ability of patients to tolerate interferon-alpha was related to the dose of zidovudine. Toxic effects of the combined zidovudine and interferon-alpha regimen included: neutropenia, a decrease in a type of white blood cells called neutrophils; fatigue; thrombocytopenia, a decrease in the number of platelets, blood cells involved in clotting; and impaired liver function. Among 22 patients who received a stable dose of both drugs over 12 weeks, the combined regimen was completely or partially effective against Kaposi's sarcoma in 11 patients and against infection with the human immunodeficiency virus (HIV) in eight patients. The results show that the combined drug regimen of zidovudine and interferon-alpha can be effective against Kaposi's sarcoma and HIV infection in patients with AIDS; this treatment may have a role in the management of these individuals. (Consumer Summary produced by Reliance Medical Information, Inc.)

Asthma is among the most common chronic diseases in the United States, afflicting greater than 10 million Americans. The most frequent cause of hospital admissions for children, asthma also leads [...]

Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4+ counts of O.2–0.5 × 109 cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-α. Mean neutropenia-inducing doses of interferon-α were 9.4 × 106 and 10.6 × 106 IU/day for groups receiving 100 or 200 mg zidovudine every 4 h, respectively. Mean GM-CSF doses used to reverse neutropenia were 0.64 and 0.63 µg/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30 µg/kg/day. Serum p24 antigen declined >70% in all 5 antigenemic patients. Toxicities included a dose-dependent increase in lymphokine-like side effects (100%), anorexia and weight loss (42%), fatigue (42%), and anemia (50%). While toxicities of the combination can be significant, low-dose GM-CSF readily ameliorated neutropenia associated with zidovudine and interferon-α therapy without adversely affecting the antiviral properties of the combination.