Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Interferon (IFN alpha) blocks replication of human immunodeficiency virus (HIV)-1 in vitro by interfering with the release of mature virions. Clinical trials have addressed the in vivo effects of IFN alpha, both alone and in combination with other agents, in a variety of patients at all stages of HIV-1 infection. Patients with late stages of HIV-1 infection (CD4 counts under 100) show few positive results following treatment with IFN alpha. Patients with earlier stages of HIV infection, however, may benefit from treatment with this agent. Several clinical trials have demonstrated the activity of interferon in the treatment of patients with acquired immunodeficiency syndrome, Kaposi's sarcoma, and CD4 counts over 200. In these trials, response rates of approximately 40% have been reported, with the probability of response directly correlated with the level of CD4 cells. These antitumor effects have been associated with declines in the circulating levels of the HIV-1 core antigen p24. alpha-Interferon activity has also been studied in patients concomitantly receiving zidovudine. In these studies, neutropenia, reversible with the concomitant administration of granulocyte macrophage colony-stimulating factor, has been the most common dose-limiting toxicity. Both the antitumor and antiviral activities of combination therapy appear to be at least as good as those observed when single agents are used. Controlled clinical trials are currently under way to evaluate the role of interferon therapy, both alone and in combination with zidovudine, in patients with early HIV infection.
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PMID:The role of alpha-interferon in patients with human immunodeficiency virus infection. 194 29

Eighteen asymptomatic men with persistent human immunodeficiency virus type 1 (HIV-1) p24 antigenemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and thereafter with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 92 weeks. Six additional HIV-1 p24 antigenemic subjects were treated with zidovudine 500 mg 12-hourly for 76 weeks. Disease progression occurred in 4 subjects, despite sustained reduction of serum HIV-1 p24 antigen levels: Pneumocystis carinii pneumonia was diagnosed after 60, 80, 90 and 93 weeks, respectively. The median CD4+ cell count of these 4 men at study entry was 0.2 x 10(9)/l, and it declined to 0.07 x 10(9)/l at the moment AIDS was diagnosed. In 20 subjects no disease progression occurred. The median CD4+ cell count of these 20 men at study entry was 0.4 x 10(9)/l and it was 0.45 x 10(9)/l at the end of the study period. Median serum HIV-1 p24 antigen levels at the end of the study period were 42% lower than at study entry in these 20 subjects. In 5/20 men, an initial decline was followed by a rise in antigen levels to above pretreatment value. Treatment with zidovudine was well tolerated. Anemia caused symptoms in 3/24 men, but prolonged leucopenia or neutropenia did not occur. None developed clinical or convincing biochemical evidence of zidovudine-associated myopathy.
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PMID:Long-term zidovudine treatment of asymptomatic HIV-1-infected subjects. 197 21

Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.
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PMID:GM-CSF as an alternative to dose modification of the combination zidovudine and interferon-alpha in the treatment of AIDS-associated Kaposi's sarcoma. 204 63

Zidovudine was used in an open uncontrolled study for treatment of 145 human immunodeficiency virus (HIV) patients, 102 with acquired immune deficiency syndrome (AIDS) and 43 with symptomatic HIV disease (acquired immune deficiency syndrome related-complex, ARC). The mean period of follow-up was 6 +/- 2.5 months. The median survival time of AIDS patients on zidovudine was 4.5 times longer when compared to a historical zidovudine untreated AIDS group (1657 vs. 370 days). This should be interpreted with reserve regarding improvements in treatment of all aspects of HIV infection and heightened awareness of AIDS which may have led to earlier diagnosis in the zidovudine treated groups. Pneumocystis carinii pneumonia (PCP) was very rarely a cause of death in zidovudine-treated patients (4.8%), while it was responsible for the death in 46.2% of historical controls (P less than 0.001). Extensive Kaposi's sarcoma was equally the cause of death in treated as well as in historical patients. Median T4 cell counts increased on zidovudine reaching a peak at the end of the fourth month of therapy in the ARC group and at the end of the first month in the AIDS group with a subsequent fall. Sixty per cent (53 of 87) patients were p24 viral antigen positive at the start of treatment and 19% of them had a fall of more than 50% in antigen level in three months while 32% became antigen negative within 2.5 months. Survival in patients where the antigen disappeared or in whom there was a major (greater than 50%) fall in antigen level was significantly higher than in those for whom there was no change in antigen level or in whom the antigen was negative at the start of the study (P less than 0.05). Forty-seven of the 145 zidovudine treated patients needed to be transfused because of anaemia. The mortality was significantly higher in this group of patients, particularly in those transfused prior to zidovudine therapy. Neutropenia occurred in four subjects. Platelets rose after the start of zidovudine but subsequently fell to thrombocytopenic levels in eight patients.
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PMID:Zidovudine treatment of patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex: St Stephen's Hospital experience. 249 85

Eighteen asymptomatic men with persistent human immunodeficiency virus type I (HIV-I) p24 antigenaemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and subsequently with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 36 weeks. After 24 weeks six additional HIV antigenaemic subjects were entered and treated directly with zidovudine 500 mg 12-hourly. Over the treatment period serum HIV-I p24 (HIV-Ag) levels declined in all 24 subjects; significantly so in 17, and to below cut-off values in five. Mean serum HIV-Ag levels in different treatment groups declined in 68-78%. Initial increases in CD4+ cell counts were not sustained. Over 48 weeks serum HIV-Ag levels rose in three out of five non-treated men with persistent HIV antigenaemia, and they slightly declined in two; the mean serum HIV-Ag level in this group rose 67%. Regression of enlarged lymph nodes was seen in 19 out of 19 of the zidovudine-treated subjects. In the 24 zidovudine-treated subjects no disease progression occurred during follow-up, whereas two out of five non-treated men went on to develop CDC group IV A, and IV C-2 disease, respectively. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in two, but serious leucopenia or neutropenia was not observed. An initial positive effect on thrombocyte numbers was not sustained. These data demonstrate that in asymptomatic HIV-infected subjects zidovudine 500 mg 12-hourly is well tolerated and has a persistent inhibitory effect on viral replication.
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PMID:Markers for progression to acquired immune deficiency syndrome and zidovudine treatment of asymptomatic patients. 249 86

The efficacy and toxicity of oral azidothymidine has been studied in 145 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The median survival time of AIDS patients on azidothymidine was 4.5 times higher when compared to a historical AIDS group who had not received the drug. This result must be interpreted with caution because of changes in treatment of HIV infection and growing awareness of AIDS which may have led to earlier diagnosis in the group treated with azidothymidine. The mortality was significantly higher in those patients who received transfusions and was particularly high in those who were transfused before azidothymidine. There was a significant difference in the occurrence of opportunistic infections in the patients who received transfusions compared with those who did not. AIDS patients treated immediately after an episode of Pneumocystis carinii pneumonia survived significantly longer than those in whom treatment was delayed for three months or more, and longer than those who were treated with azidothymidine because of another opportunistic infection or Kaposi's sarcoma. The T4 cell median counts increased in patients treated with azidothymidine reaching a peak at the end of the fourth month of treatment in the ARC group and at the end of the first month in the AIDS group with a subsequent fall in both groups. Sixty per cent of patients were p24 viral antigen positive at the start of treatment and 19 per cent of these patients had a fall of more than 50 per cent in antigen level while 32 per cent became antigen negative following treatment with azidothymidine. The mortality in the patients where the antigen disappeared or in whom there was a major fall of more than 50 per cent in antigen level was significantly less than in those where there was no change in antigen level. Twenty-nine patients were treated with azidothymidine because of skin Kaposi's sarcoma and in 17 tumour regressed or was stable. Thirty-two per cent of patients treated with azidothymidine became anaemic. Neutropenia occurred in 3 per cent of patients. Platelets increased initially after treatment but subsequently fell to thrombocytopenic levels in eight patients. Nine of 12 patients with thrombocytopenia before azidothymidine was commenced responded with an increased platelet count.
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PMID:The efficacy and toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex (ARC): an open uncontrolled treatment study. 251 92

In this double-blind, placebo-controlled trial of HIV-infected asymptomatic haemophiliacs, the efficacy of 2-year zidovudine therapy (1000 mg daily in two divided doses) in preventing progress of HIV infection was prospectively evaluated. Drug tolerance was also studied. 143 haemophiliacs from five European countries and Australia with p24 antigenaemia and/or CD4 cell counts of 0.1-0.4 x 10(9)/l were enrolled. The main measures of outcome were progression to AIDS, CDC group IV disease, symptomatic HIV-related disease, and a decrease in CD4+ T-lymphocyte count to fewer than 0.2 x 10(9)/l. There were no significant treatment differences in the proportion of patients progressing to AIDS, CDC group IV or symptomatic disease. Analysis of time to CD4+ counts less than 0.2 x 10(9)/l showed a non-significant trend in favour of zidovudine. Haemoglobin concentrations were less than 8 g/dl in 4% of zidovudine recipients; neutropenia was less than 0.75 x 10(9) cells/l in 5% of zidovudine recipients; alanine aminotransferase levels were greater than 10 times the upper normal limit in 3% of zidovudine recipients, but also in 4% of placebo recipients. Hence there was a very low prevalence of side-effects in haemophiliacs, despite the use of a higher zidovudine dosage than is currently widely used.
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PMID:Randomized double-blind, placebo-controlled trial of twice-daily zidovudine in asymptomatic haemophiliacs infected with the human immunodeficiency virus type 1. European-Australian Haemophilia Collaborative Study Group. 791 97

Human immunodeficiency virus (HIV)-infected patients may acquire invasive aspergillosis without previously recognized risk factors, such as neutropenia or corticosteroid therapy. Because neutrophils (PMNL) are an important component of host defense in aspergillosis, the antifungal activity of PMNL against hyphae of Aspergillus fumigatus in 31 HIV-infected children was assessed. Hyphal damage was unaffected in 15 HIV-infected children with age-adjusted CD4 cell counts > or = 25% of the normal median value; it was decreased in 16 with CD4 cell counts < 25% (both vs. 20 healthy controls, P = .001. Incubation with sera from 12 of 14 HIV-infected children but not with the recombinant HIV proteins gp120, gp41, and p24 suppressed antifungal activity of normal PMNL compared with normal serum (P = .002). Pretreatment of defective PMNL from 5 patients with granulocyte colony-stimulating factor (G-CSF) partially corrected the defect (P = .002). These findings suggest that impaired serum-mediated antifungal activity against Aspergillus hyphae exists in PMNL of HIV-infected patients with low CD4 cell counts; G-CSF may improve this activity.
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PMID:Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus. 845 Feb 55

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted.
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PMID:The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. 854 34

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.
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PMID:A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease. 929 87


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