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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.
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PMID:Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection. 127 53

Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.
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PMID:Granulocyte colony-stimulating factor treatment in AIDS patients. 128 Apr 96

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.
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PMID:Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program. 128 56

In an attempt to identify risk factors for Staphylococcus aureus septicemia, 136 consecutive HIV-infected patients were investigated for the presence of nasopharyngeal colonization with Staphylococcus aureus and subsequent Staphylococcus aureus infection. Sixty of 136 (44.1%) HIV-infected patients had staphylococci which were detected in the nasopharynx on initial culture compared to 12 of 39 (30.8%) patients with chronic diseases and 11 of 47 (23.4%) healthy hospital staff. Another 12 HIV-infected subjects proved to be Staphylococcus aureus carriers on follow-up cultures. Patients with full-blown AIDS had a higher carriage rate compared to subjects who were only HIV-positive (p < 0.05), indicating that Staphylococcus aureus colonized patients were more severely ill. Eight patients with Staphylococcus aureus septicemia were observed, all of whom were carriers; no septicemia occurred in the non-colonized patients (p < 0.01). Colonized patients with neutropenia (< 1000/microliters) were significantly more likely to develop septicemia (p < 0.01). Nasopharyngeal colonization with Staphylococcus aureus and the presence of an indwelling catheter were established to be factors that help identify patients at risk of acquiring subsequent Staphylococcus aureus infection.
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PMID:Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus. 129 67

The drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, frequent thrombocytopenia, and overall bone-marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of haematopoietic progenitor stem cells following exposure to anticancer drugs and/or radiation in the treatment of malignant disease. We here report the results of studies designed to evaluate the effectiveness of lithium in reversing and/or protecting against either murine or human bone marrow derived haematopoietic progenitors, i.e. (CFU-GM, CFU-Meg, and BFU-E) when co-cultured in the presence of zidovudine in vitro. Lithium chloride (LiCl) reversed zidovudine toxicity to either murine or human derived CFU-GM and CFU-Meg that was optimal at a concentration of 1 mM (P less than 0.05). However, the addition of lithium failed to influence zidovudine toxicity toward either murine or human BFU-E. In summary, these results support the scant clinical studies that have described the presence of neutrophilia and/or thrombopoiesis in zidovudine-treated AIDS patients receiving lithium. In addition, these data further confirm the need for more detailed evaluation of lithium as an adjuvant agent to reduce the haematopoietic toxicity associated with the use of antiviral therapy in HIV-infected patients.
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PMID:Effective modulation of the haematopoietic toxicity associated with zidovudine exposure to murine and human haematopoietic progenitor stem cells in vitro with lithium chloride. 131 88

The antiviral drug used in the treatment of acquired immunodeficiency syndrome, zidovudine, has proved effective in ameliorating the morbidity and mortality associated with human immunodeficiency virus infection. However, associated with zidovudine is the development of severe bone marrow toxicity manifested by anemia, neutropenia, and occasionally thrombocytopenia. We report the results of studies that demonstrate the ability of basic fibroblast growth factor (B-FGF) to reduce zidovudine toxicity to several classes of hematopoietic progenitors (granulocyte-macrophage, CFU-GM; megakaryocyte. CFU-Meg; and erythroid, BFU-E) from normal murine, human, and murine retrovirus-infected bone marrow cells when cocultured with zidovudine in vitro. Optimal response to B-FGF was observed at a dose concentration of 10 ng/ml. The specificity of B-FGF was demonstrated in the presence of protamine sulfate, an effective inhibitor of B-FGF mitogenic activity. In addition, synergistic activity of B-FGF on zidovudine-induced hematopoietic stem cell toxicity was observed in the presence of interleukin 1 (IL-1) (30 ng/ml). These studies demonstrate that B-FGF is capable of reducing the hematopoietic toxicity associated with zidovudine and that such an effect can be amplified in the presence of IL-1.
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PMID:In vitro modulation of the toxicity associated with the use of zidovudine on normal murine, human, and murine retrovirus-infected hematopoietic progenitor stem cells with basic fibroblast growth factor and synergistic activity with interleukin-1. 131 78

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression. 137 18

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors as adjuncts to antiretroviral therapy. 138 Feb 56

Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing.
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PMID:Delayed recognition of human immunodeficiency virus infection in preadolescent children. 140 40

Standard treatments of HIV-associated Pneumocystis carinii pneumonia (PCP) consist of high dose intravenous or oral cotrimoxazole or intravenous pentamidine. Both treatment modalities are associated with a high incidence of side effects which strengthen the need for alternative therapies. Since April 1987 we have used the combination of dapsone plus trimethoprim (DP+TMP) as primary treatment for PCP in patients who could be managed on an outpatient basis. We report the results of an analysis of the efficacy and toxicity of this treatment in 20 episodes of PCP in 18 patients. PCP was diagnosed by identification of the pathogens in bronchoalveolar lavage specimens. Chest X-ray revealed bilateral involvement in 11 and unilateral in 7 cases and no infiltration in one patient. Treatment over three to four weeks was successful in 14 of 20 PCPs (70%). In six cases (30%) treatment was changed to another regimen after a mean of seven days due to a maculopapular rash (n = 2), haematotoxic side effects (n = 2), persistent fever (n = 1) and for unexplained reasons (n = 1). Less severe side effects not causing a change in treatment were a slight to moderate neutropenia (n = 10), a moderate elevation of liver enzymes (n = 2) and a well tolerated rash (n = 2). The success rate of DP+TMP was in the same range as it is known for the standard regimens, whereas the rate of severe side effects appears to be lower. The results suggest that in AIDS patients DP+TMP may be used as first line treatment of PCP which is not severe enough for hospitalisation.
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PMID:[Successful treatment of HIV-associated pneumocystis carinii pneumonia with dapsone plus trimethoprim]. 141 18


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