Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Filgrastim induces lymphocytosis, including all T cell subsets, and increased ex vivo interleukin (IL)-2 release as well as lymphocyte proliferation. Since Filgrastim is increasingly used in patients with human immunodeficiency virus (HIV) infection, the effect of Filgrastim on ex vivo cytokine production was determined. Whole blood from 8 healthy volunteers, 5 high-risk volunteers, and 31 HIV-infected outpatients was assayed for cytokine production in response to endotoxin (LPS) or staphylococcal enterotoxin B (SEB) in the presence or absence of 100 ng/mL Filgrastim. LPS-inducible blood cytokine release of HIV-infected patients was not different from that of normal or high-risk volunteers. The suppressive effect of Filgrastim on LPS-inducible blood tumor necrosis factor-alpha and interferon-gamma formation in normal volunteers was not found in HIV-infected patients. Patients with advanced HIV infection showed reduced IL-2 and IL-4 release in the presence of SEB. In the presence of Filgrastim, IL-2 production was partially restored.
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PMID:Filgrastim restores interleukin-2 production in blood from patients with advanced human immunodeficiency virus infection. 972 36

Hematopoietic growth factors are well known to increase neutrophil counts and support the administration of myelotoxic and myelosuppressive therapies, especially chemotherapies. Filgrastim (r-metHuG-CSF) has been used in the setting of HIV disease to treat neutropenia and HIV-associated neutrophil defects. This article reviews the biology, product characteristics, and preclinical and clinical development of Filgrastim. Emphasis is given on the use of Filgrastim in the setting of HIV infection and AIDS.
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PMID:Biopharmaceutical drug development: Filgrastim (r-metHuG-CSF) use in patients with HIV infection. 1059 29

Neutropenic individuals are at high risk for bacterial and fungal infections. Filgrastim (r-metHuG-CSF, NEUPOGEN) has been shown to improve chemotherapy-induced neutropenia significantly. Because a high incidence of HIV-infected patients have neutropenia, often associated with myelosuppressive antiretroviral medication, Filgrastim is frequently used as a treatment strategy for this HIV-associated neutropenia. This review summarizes published work related to the use of Filgrastim in HIV-infected patients. Literature bases (EMBASE, MEDLINE, Int. Pharm. Abs., SciSearch, and Aidsline) from 1970 to 1998 were searched for articles describing the relationship of Filgrastim and ANC to bacterial infection rates, bacterial infection outcome, and overall survival. Thirty-five related articles were identified during this search. Filgrastim appears to have a significant role in increasing peripheral ANC and enhancing neutrophil function in patients with HIV infection and AIDS. This may translate into a clinical benefit of delivery of full-dose myelosuppressive antiretroviral therapy and decreased susceptibility to infections and increased survival in this patient population.
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PMID:The use of Filgrastim in AIDS-related neutropenia. 1059 30

Data have shown that neutropenia is a risk factor for severe bacterial infections. Two trials were done in HIV-infected patients to study the effect of Filgrastim on neutropenia and the incidence of severe bacterial infections. The incidence of Mycobacterium avium complex (MAC) infection in this setting was also evaluated. This paper reviews the results of these two studies, which suggest that Filgrastim is safe and effective in preventing severe neutropenia in patients with advanced HIV infection.
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PMID:Clinical experience with Filgrastim in AIDS. 1059 31

G-CSF has immunomodulatory effects of neutrophilic granulocytes and monocytes/macrophages. Two studies were done: one in normal volunteers and the other in HIV-infected patients plus their respective control donors to evaluate the effect of Filgrastim on cytokine responses. Filgrastim treatment of volunteers resulted in an anti-inflammatory cytokine response, when blood was stimulated ex vivo with the endotoxin lipopolysaccharide (LPS). Similarly, in the presence of Filgrastim in vitro, the LPS-inducible release of proinflammatory cytokines was attenuated. Blood from HIV-infected patients at advanced stages of disease showed reduced interleukin (IL)-2 formation in response to staphylococcal exotoxin B (SEB), which was restored in the presence of Filgrastim.
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PMID:Anti-inflammatory aspects of Filgrastim and impact on IL-2 release. 1059 32

In a study of 258 moderately neutropenic HIV-infected patients, Filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) treatment significantly reduced the incidence of severe neutropenia and bacterial infections. Filgrastim-treated patients also had 54% fewer severe bacterial infections and 45% fewer days in hospital for any bacterial infections. No unexpected or new adverse events were observed and there were no differences in plasma HIV-1 RNA levels between the groups.
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PMID:Prevention of bacterial infections in patients with advanced HIV infection. 1059 77

The effect of Filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) treatment on neutrophil function was studied in HIV-infected patients. Filgrastim therapy significantly increased oxidative capacity of neutrophils, increased bacterial killing, and reduced accelerated apoptosis of neutrophils observed in this patient population.
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PMID:Filgrastim treatment of HIV-infected patients improves neutrophil function. 1059 78

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)
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PMID:Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team. 1060 83

Neutropenia frequently complicates infection due to human immunodeficiency virus (HIV). The etiology of neutropenia in this setting includes bone marrow infection or infiltration, myelosuppressive therapies, the presence of antibodies to HIV, and accelerated apoptosis. Protection against microbial invaders by neutrophils is further compromised by impaired chemotaxis and phagocytosis, production of toxic oxygen species, and expression of cellular adhesion molecules. Neutropenia is a significant risk factor for bacterial infection in HIV-infected patients. Endogenous cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, regulate neutrophil count and function. Treatment with recombinant human methionyl G-CSF (filgrastim) has lessened neutropenia in patients with HIV infection. Clinical trials have shown that the incidence of bacterial infections and the number of consequent days of hospitalization for HIV-infected patients receiving filgrastim therapy are lower. Filgrastim treatment also allows administration of larger doses of myelosuppressive agents.
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PMID:Neutropenia, neutrophil dysfunction, and bacterial infection in patients with human immunodeficiency virus disease: the role of granulocyte colony-stimulating factor. 1067 24

Topotecan, a drug typically used to treat cancer, has shown promising in vitro results against the JC virus. The JC virus causes progressive multifocal leukoencephalopathy (PML). SmithKline Beecham is planning to announce phase II placebo-controlled trials for PML. There is currently no known treatment for PML, although it sometimes responds to anti-HIV drugs, alpha-interferon, and peptide T. AIDS advocates are questioning why SmithKline Beecham did not perform animal and pre-clinical studies to see if topotecan would be effective and tolerable among HIV/AIDS patients. Topotecan treatment has resulted in minimum success fighting ovarian cancer, however, its toxic effects are dangerous and powerful. Advocates advise that any patient considering a trial of topotecan have their blood monitored very carefully, particularly for neutropenia. Participants should consider pre- and post-treatment with G-CSF (Neupogen) to boost white blood cells.
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PMID:Topotecan and PML: the limits of pharmaceutical industry research. 1136 13


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