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

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.
 ...
PMID:Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. 238 74

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
 ...
PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

The safety and activity of several antiretroviral agents are being evaluated for treatment of acquired immunodeficiency syndrome (AIDS) in infants and children. Intermittent oral and intravenous regimens and continuous intravenous infusion of the dideoxynucleoside, 3'-azido-3'-deoxythymidine (zidovudine, AZT), have been shown to be beneficial in improving neuro-developmental function and growth velocity in pediatric patients with AIDS. AZT, however, is limited by the associated development of neutropenia and anemia, which frequently necessitates transfusions. Another dideoxynucleoside, 2',3'-dideoxycytidine (ddC), also shows theoretical promise in the treatment of the pediatric AIDS population. This agent is not associated with the hematologic toxicity induced by AZT but does produce a painful sensory peripheral neuropathy. Sequential therapy with AZT and ddC may limit the toxic effects associated with the use of these drugs individually. Dideoxyinosine and soluble recombinant CD4 are two newer antiretroviral agents that are under investigation for the management of AIDS in infants and children. The activity of recombinant CD4 in preventing the transplacental transmission of human immunodeficiency virus is also being evaluated.
 ...
PMID:Treatment of human immunodeficiency virus-infected infants and young children with dideoxynucleosides. 215 4

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.
 ...
PMID:Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group. 218 Nov 2

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.
 ...
PMID:Zidovudine update: 1990. 219 18

A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease.
 ...
PMID:[Evaluation of the pharmacovigilance follow-up of zidovudine]. 226 33

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.
 ...
PMID:Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection. 234 66

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.
 ...
PMID:Zidovudine treatment of patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex: St Stephen's Hospital experience. 249 85

AZT is now the standard of care for all persons with AIDS, ARC or T4 helper cell levels less than 200/mm3. Some authorities are cautiously recommending it with full informed consent for patients who have fewer than 400 mm3 T4 cells or who have sustained a rapid fall in helper cells coupled with new symptoms. The optimum dosage remains to be determined. Although the package insert recommends 200mg p.o. q. 4 hours, b.i.d. and Q6 hour dosage regimes have been reported as being as effective with less toxicity. Folate and B12 levels should be measured and replaced when appropriate to avoid undue hematologic toxicity and therapy should be interrupted for hemoglobin less than 7.5 or neutropenia consisting of fewer than 750 leukocytes/cc. For progressive, less severe marrow toxicity the dose may be decreased to avoid a prolonged nadir. A CBC should be obtained every two weeks for at least the first eight weeks and monthly thereafter if counts are stable. Other toxicities to be monitored include elevated transaminases and co-administration with medications that affect hepatic glucuronidation such as probenecid, NSAID's and acetaminophen. In the eight years since this epidemic appeared on the medical horizon much has been learned about the disease and its treatment. More and more physicians are willing and eager to assume primary care responsibilities for their patients with AIDS and it is hoped AZT and other effective therapies will assist them in this process.
 ...
PMID:AIDS in Arkansas. Zidovudine: an overview and rationale for use. 252 34

30 patients with recurrent zidovudine-induced neutropenia were followed up for a total of 493 months of treatment to evaluate their risk of bacterial infection. Zidovudine was temporarily discontinued only when the polymorphonuclear (PMN) cell count fell to less than 500/microliters. The incidence of bacterial infection during periods of severe neutropenia (PMN less than 500/microliters) was 230% higher than when the PMN count was 500-1000/microliters, and 600% higher than when the count was greater than 1000/microliters. The difference between periods when the PMU count was 500-1000/microliters and non-neutropenic periods was not significant. The findings suggest that zidovudine therapy can be continued despite neutropenia without a major increase in the incidence of bacterial infection provided the PMN count does not fall to less than 500/microliters.
 ...
PMID:Zidovudine-induced neutropenia: are we too cautious? 256 82


<< Previous 1 2 3 4 5 6 7 Next >>