losartan-potassium and Acquired-Immunodeficiency-Syndrome

Anemia is common in persons with HIV infection and is associated with poor prognosis. There is a need to assess the effects of anemia treatments, and to determine whether these interventions are beneficial.. To determine the efficacy and safety of treatments for anemia in people with HIV infection and AIDS.. The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 10, 2010), MEDLINE (1980-November 25, 2010), EMBASE (1980-November 25, 2010), LlLACS (1982 to November 25, 2010), Africa Index Medicus (up to November 9, 2010), ISI Web of Knowledge (2005 to October 9, 2010), Scirus (October 9, 2010) reference lists of relevant articles. We asked the Cochrane HIV/AIDS and Pregnancy and Childbirth Groups to check their Specialised Registers. We also checked the reference lists of all trials identified by the above methods.. Randomized trials assessing the effects of treatments for anemia in people diagnosed with HIV infection. There were no age restrictions.. Two authors independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by two authors and checked by the other two authors.. Six trials with a high risk of bias, including 537 patients, met the inclusion criteria. These trials only covered recombinant Human erythropoietin alfa (rHuEPO). Two of them including adult and paediatric participants (84 participants and 4 events) comparing rHuEPO to placebo did not reduce the risk of mortality with a follow up to 12 weeks (pooled RR 0.56, 95% confidence interval (CI) 0.08 to 4.05, I(2) = 0%). Any trials that compared rHuEPO to placebo did not show any benefit on hematological values response, number of patients transfused, or number of packed red cell transfused. Two trial compared the effects of two rHuEPO dosing regimens on hemoglobin value and quality of life, but the effects are unclear. Three RCT reported high risk of attrition bias; therefore, were not included in a meta-analysis.. This updated Cochrane review provides evidence that rHuEPO compared with placebo does not reduce mortality, does not reduce transfusion requirements, did not increase hemoglobin levels, and did not improve quality of life in HIV-infected patients with anemia. The results are based on six RCTs with high risk of bias. Therefore prescription of this intervention for treating anemia in patients with AIDS is not justified, unless new evidence from a large high quality trial alters this conclusion.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Hematinics; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is a common clinical disease in persons with HIV infection and is associated with poor prognosis. There is a need to assess the effects of anemia treatments, and to determine whether these interventions are beneficial.. To determine the efficacy and safety of treatments for anemia in people with HIV infection and AIDS.. The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1980-July 2005), EMBASE (1980-July 2005), LlLACS (1982 to July 2005), reference lists of relevant articles and contact with authors. See Cochrane HIV/AIDS Group search strategy.. Randomized trials assessing the effects of treatments for anemia in people diagnosed with HIV infection. There were no age restrictions.. Both authors independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by one author and checked by the other author.. We included four trials, but focused on the results based on three trials with acceptable attrition rate. None of the trials reported data on death. The two trials that compared recombinant human erythropoietin (rHuEPO) to placebo did not show any benefit on hematological values response, number of patients transfused, or number of packed red cell transfused. One trial compared the effects of two rHuEPO dosing regimens on hemoglobin value and quality of life, but the effects are unclear.. There is a lack of reliable evidence on interventions for treating anemia in patients with HIV infection. This Cochrane review has found some evidence that rHuEPO reduces transfusion requirements, increases hemoglobin levels, and improves quality of life in HIV-infected patients with anemia. However, this is based on evidence from randomized trials with weak or poor methodological quality. There is a need for randomized trials of high methodological quality to evaluate the effect of interventions on anemia in persons infected with human immunodeficiency virus.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

There is a close association between the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, infection and immunity. Infection with the human immunodeficiency virus (HIV) is often associated with a decrease of the concentrations of IGF-I, IGF-II, IGF-binding protein 3 (IGFBP-3) and an increase of IGFBP-1 and -2. Many investigators have studied the relationship between the GH-IGF-I system and some of the most common characteristics of disease progression, such as decreased CD4 cell counts, weight loss and fat redistribution. Although conditions for restoration of thymic function and lymphopoiesis with GH or IGF-I are still not well defined, many studies led to the development of clinical trials on the therapeutic use of GH, IGF-I and GHRH for the treatment of weight loss or fat redistribution, two problems which persist despite the introduction of highly active antiretroviral therapy. Monitoring IGF-I concentrations during treatment with GH and GHRH is likely to become an essential component of their therapeutic use. IGF-I levels are the first indicator of treatment efficacy and can be used to monitor compliance. High levels of IGF-I are a warning sign for the increased risk of potential adverse effects, such as acromegalic-like symptoms or malignancy. This could lead to a reduction of the therapeutic dose or the temporary interruption of treatment until IGF levels reach a safe range. IGF-I levels are also likely to increase with other hormones used in HIV patients, such as erythropoietin for the treatment of anemia or anabolic androgens in HIV-infected women.

Topics: Acquired Immunodeficiency Syndrome; Androgens; Erythropoietin; HIV Infections; Humans; Somatomedins

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Bone marrow suppression is a substantial problem in patients infected with HIV. Contributing factors include the underlying HIV infection, alterations in the marrow microenvironment (resulting in abnormal cytokine regulation of hematopoiesis), and opportunistic infections and their associated medical treatments. Hematopoietic stimulants offer the promise of correcting peripheral blood cytopenias, augmenting host immune function, and permitting the continued use of potentially beneficial myelosuppressive therapies, which would otherwise result in dose-limiting side effects. The bone marrow abnormalities and mechanisms that contribute to alterations in hematopoiesis in HIV infection are briefly reviewed. Attention is then focused on the expanding clinical role of myeloid colony-stimulating factors (CSFs) and recombinant human erythropoietin (rHuEPO [Epogen, Procrit]) in the treatment of patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Bone Marrow; Bone Marrow Diseases; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Humans; Neutropenia; Neutrophils; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Erythropoietin; Humans; Hypertension; Neoplasms

The anaemia of chronic disease is the second most common anaemia in the world and is an underproduction anaemia with relatively low erythropoietin (EPO) values for the degree of the anaemia. This anaemia occurs with inflammation, infection, or malignancy and a principle question has been whether it would respond to recombinant human EPO (r-HuEPO). Several studies are now available to answer this question. In one study 12 of 16 patients with rheumatoid arthritis receiving r-HuEPO increased their haematocrits 6 percentage points or more and 11 of 12 reached normal haematocrits. Investigations of the effect of r-HuEPO on the anaemia of AIDS showed that patients with EPO levels of 500 U/L or less had an increase in the mean haematocrit of 4.6 percentage points with a decrease in red cell transfusions from 5.3 to 3.2 units per patient. Quality of life indices significantly improved in responders. When 413 patients with anaemia due to a wide variety of malignancies were randomized to r-HuEPO treatment, 58% of those receiving chemotherapy increased their haematocrits by at least 6 points over 12 weeks. Quality of life parameters of responders also significantly improved. Anaemia in three patients with inflammatory bowel disease also responded in 8-14 weeks to r-HuEPO and two of the three reached normal haemoglobin levels. It is clear that r-HuEPO can correct the anaemia of chronic disease and can improve the quality of life of responders.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Erythropoietin; Humans; Inflammatory Bowel Diseases; Neoplasms; Recombinant Proteins

Erythropoietin (EPO) is a glycoprotein produced primarily by the kidney in response to tissue hypoxia, and is the principal factor regulating red blood cell production. It stimulates erythroid precursors in the bone marrow to proliferate and mature into morphologically identifiable red blood cells. This hormone acts by binding to specific high-affinity receptor on erythroid precursors. Failure to produce adequate quantities of EPO leads to severe anemia, a situation most often encountered in patients with end stage renal disease. With the application of recombinant DNA technology, the gene for this hormone has been molecularly cloned, sequenced and expressed in a biologically active form in mammalian cells. The recombinant EPO has been demonstrated to correct anemia in patients with severe end stage renal disease and alleviate their transfusion requirements. It has also been studied for anemia associated with HIV infection/zidovudine therapy, in cancer, rheumatoid arthritis, and prematurity. In addition it has been studied as a facilitator of autologous blood predeposit in patients scheduled for elective surgery and as a perisurgical adjuvant to hasten hematologic recovery and possibly avoid the need for homologous transfusion after elective surgery. When administered with the current guidelines EPO appears to be safe drug with favorable risk/benefit ratio.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

The anemia of chronic disease may be viewed simply as the anemia that accompanies chronic inflammatory, infectious, or neoplastic disorders. Because these conditions are very common, the anemia of chronic disease is one of the most frequent anemias encountered, and is only second in incidence to iron-deficiency anemia. The anemia of chronic disease is primarily an anemia due to underproduction of red cells, with low reticulocyte production, and is most often a normochromic, normocytic anemia. However, in 30% to 50% of patients, the red cells are hypochromic and microcytic and, most often, the serum iron, total iron-binding capacity, and transferrin saturation are reduced in the presence of adequate iron stores. Although the differential diagnosis includes other underproduction anemias, such as those caused by vitamin and mineral deficiencies, renal failure, endocrinopathies, and myelodysplasia, it generally is easily distinguished from these conditions. Nevertheless, an understanding of the pathogenesis of this condition, as well as a means of alleviating the anemia when the chronic disorder persists, has remained elusive. Recently, major advances have occurred toward understanding the pathogenesis of the anemia of chronic disease and its treatment, and these advances are reviewed.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Anemia, Hypochromic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Cytokines; Erythropoietin; Humans; Incidence; Neoplasms; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Bone Marrow Transplantation; Colony-Stimulating Factors; Erythropoietin; Hematopoietic Cell Growth Factors; Humans; Neoplasms; Neutropenia; Tumor Necrosis Factor-alpha; Zidovudine

Hematopoietic growth factors may mitigate the cytopenias that frequently complicate HIV disease or its treatment. Clinical and in vitro studies have indicated the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) to overcome the myelosuppression of HIV or many of the drug therapies used in the care of HIV-infected individuals. In addition, neutrophil or monocyte functional abnormalities observed in AIDS patients may be improved by the use of GM-CSF. Issues which may distinguish the use of hematopoietic growth factors in AIDS as compared with in other clinical settings include: 1) interaction of the growth factor with other cytokines which are aberrantly expressed, 2) direct effects of the growth factor on the replicative activity of HIV, and 3) potential interactions of the growth factor with other concurrently administered medications. This review focuses on the potential roles and limitations of growth factor use in AIDS and reviews the clinical studies using GM-CSF in HIV-infected individuals.

Topics: Acquired Immunodeficiency Syndrome; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; HIV Infections; Humans; Leukocyte Count; Monocytes; Neutropenia; Neutrophils

Three hematopoietic growth factors, erythropoietin, GM-CSF, and G-CSF, have all been evaluated in the context of HIV infection. Recombinant human Epo is currently licensed for therapy of anemia related to zidovudine and is well tolerated in this patient population. Although myelosuppression can clearly be overcome using recombinant human GM-CSF or G-CSF in HIV-infected hosts, the clinical benefits for such patients are still not determined. It is likely that these growth factor therapies will allow for delivery of certain important myelosuppressive medications that otherwise could not be tolerated. Improvements in virological quantitation in vivo should help settle the controversies regarding modulation of HIV replication caused by cytokine treatment. The clinical use of hematopoietic growth factors in HIV disease requires further study with regard to the optimization of increases in blood cell number and/or modulation of blood cell function.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; Humans; Interleukin-3; Virus Replication

The haemopoietic growth factors are a diverse group of hormones with effects on different haemopoietic cell lineages and at various points in their developmental differentiation. The biology of many of these factors is now well understood. They have entered clinical trials and have demonstrated benefits in particular clinical situations. The thrust of current phase II and III clinical investigations now is to use these factors, alone or in combinations, to modify various disease states and to ameliorate many of the side-effects of other therapeutic agents, particularly cytotoxic anticancer agents. Many other disease states also lend themselves to therapy with these growth factors. Other haemopoietic growth factors have not been as extensively studied in humans but hold great promise. In this chapter, the current status of the haemopoietic growth factors presently under clinical trial has been reviewed. In addition, several factors which have been recently described but which have not yet entered clinical trials have been discussed.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antineoplastic Agents; Bone Marrow Diseases; Bone Marrow Transplantation; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Erythropoietin; Haplorhini; Hematologic Diseases; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Immunologic Factors; Leukemia, Myeloid, Acute; Mice; Neoplastic Stem Cells; Neutropenia; Recombinant Fusion Proteins

The emergence of the acquired immunodeficiency syndrome (AIDS) has fueled concerns of both physicians and their patients about safety of blood transfusions. Although AIDS has generated the most fear, the risk today is extremely remote (1/60.000 units of blood). The risk of transmitting infectious disease by homologous transfusion is decreasing, as more donor screening and testing measures are implemented. The blood supply is safer that at any time, but small transfusion risks exist. The most common problems associated with transfusions are temporary: one in 100-300 recipients will experience fever or rash. The biggest problem is a mismatch of the well-known ABO blood groups and once in every 100-400.000 transfusions the hemolytic reaction is fatal. Viral hepatitis is another serious and important risk. At present hepatitis seems to strike between 1 and 3 percent of transfusion recipients. Most, if not all, of transfusion-associated hepatitis cases are caused by hepatitis C virus. Cytomegalovirus can cause primary infection, reactivation or reinfection by transfusion. Immunosuppressed patients are more likely to develop more severe disease. Epstein-Barr virus does not seem to cause significant post-transfusion disease. Bacterial or protozoal infections are an infrequently encountered adverse effect of transfusion. However, some clinical cases document the potential hazard of blood components as a vector for bacteria or protozoa. Homologous blood transfusion down-regulates some immune functions. Host defences against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Donors; Blood Transfusion, Autologous; Deamino Arginine Vasopressin; Epoprostenol; Erythropoietin; Female; Graft vs Host Disease; Hemodilution; Hepatitis, Viral, Human; Humans; Infant, Newborn; Infections; Male; Pregnancy; Prognosis; Protozoan Infections; Risk Factors; Transfusion Reaction

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Bone Marrow; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Sarcoma, Kaposi; Zidovudine

In the paper the role of interleukin-3, granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), in the proliferation and differentiation of haemopoietic cells and pathogenesis of leukaemia are reviewed. Role of erythropoietin, thrombopoietin and other thrombopoiesis-stimulating factors in the development of hematopoietic is presented. Potential applications of recombinant haemopoietic growth factors in the treatment of myelodysplastic syndromes. AIDS and other haematologic, infections and neoplastic disorders are also discussed.

Topics: Acquired Immunodeficiency Syndrome; Erythropoietin; GPI-Linked Proteins; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Diseases; Hematopoiesis; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Interleukin-3; Membrane Glycoproteins; Mesothelin; Proteins

The last few years have seen an enormous increase in our knowledge on the haematopoietic growth factor erythropoietin (Epo), firstly with its purification and determination of its primary amino acid sequence, and more recently with the isolation of the Epo gene and its expression in mammalian cell lines. This review article summarizes the crucial biological features of Epo and critically examines the main results obtained in clinical trials on humans.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Animals; Erythropoietin; Humans; Kidney Diseases; Neoplasms; Recombinant Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Drug Evaluation; Erythropoiesis; Erythropoietin; Forecasting; Hematopoietic Cell Growth Factors; Humans; Immunologic Factors; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neutropenia; Radiation Injuries; Recombinant Fusion Proteins

I have reviewed areas of development in the use of blood and blood products, placing emphasis on the complications of transfusion, particularly transmission of infection. Alloimmunization in relation to transfusion of red cells and platelets has been covered and suggestions for reducing this problem assessed. The potential methods of avoiding the infective complications have been discussed including the screening of blood for infective agents, the virucidal treatment of blood products during the manufacturing process and white cell depletion. The use of recombinant DNA technology to produce coagulation factors offers the possibility of further reducing infective risks. An area of clinical promise is the use of haematopoietic growth factors to treat bone marrow failure, either congenital or acquired, such as the myelosuppressive effects of cancer chemotherapy, and reduce reliance on blood products. The aim of the chapter is to encourage the rational use of a limited resource by considering the risks inherent in transfusion and alternative strategies. In doing this it is important to audit current and future practice, and it is suggested that reference is made to the suggestions of Hume (1989) for quality assessment and assurance in paediatric transfusion medicine.

Topics: Acquired Immunodeficiency Syndrome; Blood Coagulation Factors; Blood Group Antigens; Blood Platelets; Blood Specimen Collection; Blood Transfusion; Blood Transfusion, Intrauterine; Child; Child, Preschool; Colony-Stimulating Factors; Erythrocyte Transfusion; Erythropoietin; Female; Fetal Blood; Fetal Diseases; Hemoglobinopathies; Humans; Immunization; Immunization, Passive; Incidence; Infant; Neoplasm Recurrence, Local; Platelet Transfusion; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Diagnosis; Thrombocytopenia; Transfusion Reaction; Virus Diseases

The development and widespread availability of recombinant products will effect blood centers through reduced product use, replacement of current products, and novel applications of new products. The greatest amount of clinical experience to date has dealt with the use of recombinant human erythropoietin (r-HuEPO) in the treatment of anemia in end-stage renal failure. Data also support its use in anemia associated with acquired immune deficiency syndrome (AIDS), cancer, and chronic inflammatory diseases. This article will focus on the effect of erythropoietin on the demand for erythrocyte use.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Hepatitis; Humans; Recombinant Proteins; Transfusion Reaction

Three hematopoietic stimulants have been used in patients with HIV infection and a variety of AIDS-related complications. Both G-CSF and GM-CSF have demonstrated the ability to correct leukopenia related to HIV infection and ameliorate the drug-related myelosuppressive effects of zidovudine, trimethoprim/sulfamethoxazole, ganciclovir, and, in the case of GM-CSF, alpha-interferon, and cancer chemotherapies. Erythropoietin has been successfully used to ameliorate the anemia associated with HIV infection and zidovudine therapy. Treatment with these hematopoietic stimulants is very well tolerated with minimal toxicity. Of the granulocyte stimulants, G-CSF appears to induce fewer side effects than GM-CSF in trials conducted to date. Future trials demonstrating that the amelioration of hematopoietic suppression by the colony-stimulating factors results in increased clinical response rates and improved survival are necessary to fully assess the value of this approach in the care of HIV-infected patients.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Lymphoma, Non-Hodgkin; Sarcoma, Kaposi; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Growth Substances; HIV Infections; Humans

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Erythropoiesis; Erythropoietin; Evaluation Studies as Topic; Female; Humans; Male; Postoperative Care; Preoperative Care; Recombinant Fusion Proteins; Surgical Procedures, Operative; Transfusion Reaction; Treatment Refusal

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Blood Transfusion, Autologous; Erythropoietin; Humans; Hypertension; Inflammation; Iron; Kidney Failure, Chronic; Recombinant Proteins; Vascular Resistance

Recombinant human erythropoietin (rHuEpo) has now been in clinical trials for over four years. rHuEpo has been shown to be nearly uniformly effective in correcting the anaemia of patients on haemodialysis or patients with progressive chronic renal failure not yet on dialysis. rHuEpo has been shown to be effective in increasing the ability of individuals to donate blood for self-use and to increase the haematocrit in patients with rheumatoid arthritis. Preliminary results indicate that rHuEpo will decrease transfusion requirements of patients with the acquired immune deficiency syndrome who are anaemic. Trials in patients with anaemia associated with cancer or myelodysplastic syndromes are in early stages. rHuEpo will have a major impact as a therapeutic agent, particularly in patients with renal disease.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Anemia, Aplastic; Colony-Stimulating Factors; Erythropoietin; Hematologic Diseases; Hematopoiesis; Humans; Myelodysplastic Syndromes; Recombinant Proteins

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

To evaluate the effect of recombinant human erythropoietin on anemia and health-related quality of life in patients with acquired immunodeficiency syndrome (AIDS), we initiated an observational study with an open-label multicenter treatment protocol that involved multiple academic and community physicians in the United States. Our subjects comprised 251 anemic (i.e., hematocrit < 30%) patients with a clinical diagnosis of AIDS using 1987 CDC criteria, age > or = 12 years, and serum erythropoietin level < or = 500 IU/L. The initial dosage of recombinant human erythropoietin was 4,000 units subcutaneously for 6 days each week. Based on the patient's response to therapy, the dosage was increased sequentially to 8,000 units subcutaneously for 6 days per week. Our measurements included changes in mean hematocrit and health-related quality of life. The interview included measures of energy/fatigue; physical, social, role and cognitive function; depression; health perceptions; and life satisfaction. Adverse experiences were also documented to assess safety. Changes in mean hematocrit level from a baseline of 27.9% to 33.6% at week 12 (p < .0001) and 34.5% at week 24 (p < .0001) were observed in patients treated with recombinant human erythropoietin. Adverse experiences, not clearly associated with AIDS, were reported by 10% of patients. Increases in energy (p < .05) were observed after 12 and 24 weeks of drug therapy, and increases in health perceptions were seen after 24 weeks (p < .05). No statistically significant increases or decreases were observed on measures of physical functioning, cognitive functioning, depression, social functioning, or home management activities over the 24-week follow-up. Anemia correctors (defined as hematocrit > or = 38%) showed greater improvement in energy, health perceptions, home management, and role function than noncorrectors. Study dropouts and those who died had significantly worse scores for health-related quality of life at baseline compared to study completers. Thus, the AIDS patients with anemia and serum erythropoietin levels < or = 500 IU/L treated with recombinant human erythropoietin showed increased mean hematocrit and improved health perceptions and energy levels. The drug therapy was associated with increased feelings of energy, but it was not associated with other changes in health status and well-being in the AIDS patients completing the study. These observations need to be confirmed in randomized clinical tria

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Health Status; Hematocrit; Humans; Injections, Subcutaneous; Male; Quality of Life; Recombinant Proteins; Regression Analysis; Treatment Outcome; Zidovudine

Anemia associated with human immunodeficiency virus infection may be due to reduced erythropoiesis related to the disease itself or to concomitant medications (eg, zidovudine). Clinical studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in correcting the anemia of zidovudine-treated patients infected with human immunodeficiency virus with baseline serum erythropoietin levels of 500 U/L or less. A treatment investigational new drug protocol that provided r-HuEPO to 1943 anemic patients with the acquired immunodeficiency syndrome was studied.. Enrollment criteria included a clinical diagnosis of acquired immunodeficiency syndrome, serum erythropoietin level of 500 U/L or less, hematocrit less than 0.300, and age of 12 years or more. The initial r-HuEPO dosage was 4000 U subcutaneously for 6 days each week. On the basis of response, the r-HuEPO dosage could be increased sequentially to 8000 U subcutaneously for 6 days per week. This was an open-label multicenter treatment protocol. A total of 1943 patients were treated by 510 investigators. Efficacy evaluations were based on the effect of r-HuEPO on hematocrit levels and transfusion requirements relative to baseline. Adverse experiences that were considered by the investigator to be possibly related to r-HuEPO therapy were collected to assess safety.. Therapy with r-HuEPO resulted in an increase in mean hematocrit from a baseline of 0.280 to 0.331 at week 12 and 0.338 at week 24. This increase was sustained throughout the course of the study to week 54. Overall, 40% of patients (769/1943) required at least one transfusion in the 6-week interval immediately preceding study entry (baseline). After 12 and 24 weeks of r-HuEPO treatment, corresponding percentages were 22% (311/1387) and 18% (119/650), respectively. Response to therapy, defined as an increase of 0.060 from baseline in hematocrit, with no transfusions within 28 days before achieving that hematocrit, was observed in 44% of patients. Adverse experiences not clearly related to acquired immunodeficiency syndrome were reported by 11% of patients.. In a study population of 1943 anemic patients with acquired immunodeficiency syndrome treated with r-HuEPO, the hematocrit increased and blood transfusion requirements decreased. Therapy with r-HuEPO was well tolerated.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Anemia; Blood Transfusion; Combined Modality Therapy; Drugs, Investigational; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Recombinant Proteins; Treatment Outcome; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anemia; Erythropoietin; Histoplasmosis; Humans; Recombinant Proteins; Zidovudine

Hematopoietic growth factors may mitigate the cytopenias that frequently complicate HIV disease or its treatment. Clinical and in vitro studies have indicated the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) to overcome the myelosuppression of HIV or many of the drug therapies used in the care of HIV-infected individuals. In addition, neutrophil or monocyte functional abnormalities observed in AIDS patients may be improved by the use of GM-CSF. Issues which may distinguish the use of hematopoietic growth factors in AIDS as compared with in other clinical settings include: 1) interaction of the growth factor with other cytokines which are aberrantly expressed, 2) direct effects of the growth factor on the replicative activity of HIV, and 3) potential interactions of the growth factor with other concurrently administered medications. This review focuses on the potential roles and limitations of growth factor use in AIDS and reviews the clinical studies using GM-CSF in HIV-infected individuals.

Topics: Acquired Immunodeficiency Syndrome; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; HIV Infections; Humans; Leukocyte Count; Monocytes; Neutropenia; Neutrophils

Three hematopoietic growth factors, erythropoietin, GM-CSF, and G-CSF, have all been evaluated in the context of HIV infection. Recombinant human Epo is currently licensed for therapy of anemia related to zidovudine and is well tolerated in this patient population. Although myelosuppression can clearly be overcome using recombinant human GM-CSF or G-CSF in HIV-infected hosts, the clinical benefits for such patients are still not determined. It is likely that these growth factor therapies will allow for delivery of certain important myelosuppressive medications that otherwise could not be tolerated. Improvements in virological quantitation in vivo should help settle the controversies regarding modulation of HIV replication caused by cytokine treatment. The clinical use of hematopoietic growth factors in HIV disease requires further study with regard to the optimization of increases in blood cell number and/or modulation of blood cell function.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; Humans; Interleukin-3; Virus Replication

To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy.. Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials.. Multiple centers in the United States.. Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety.. Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks.. Changes in mean hematocrit, transfusion requirement, and quality of life.. Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections.. Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Statistics as Topic; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Double-Blind Method; Erythropoietin; Humans; Multicenter Studies as Topic; Recombinant Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Anemia; Blood Transfusion; Erythropoietin; Female; Humans; Male; Middle Aged; Recombinant Proteins

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia; Blood Transfusion; Bone Marrow; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Double-Blind Method; Erythropoietin; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anemia; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Erythropoietin; Ganciclovir; Humans; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Clinical Trials as Topic; Drug Administration Schedule; Erythropoietin; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Megaloblastic; Danazol; Erythropoietin; Humans; Male; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Anemia, Aplastic; Autoantibodies; Erythropoietin; Heart Transplantation; HIV-1; Humans

Erythropoietin (EPO) is commonly used to treat anemias secondary to renal failure, malignancy, and AIDS. Although therapeutic complications are well described, overdose is rare. A 42-y-o man with AIDS confused his instructions for self-administration of interferon and EPO and began injecting himself daily with 10,000 units of EPO for several weeks. He presented with confusion, pain in his abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin remained between 12-14 g/dL and symptoms resolved. His only sequelae involved skin loss over his toes, which did not require grafting. This rare case of EPO overdose highlights the complications of essential erythrocytosis, with central nervous system, peripheral, and presumed mesenteric ischemia.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cytapheresis; Diagnosis, Differential; Drug Overdose; Emergency Treatment; Erythropoietin; Humans; Male; Sarcoma, Kaposi

We assessed zinc protoporphyrin (ZPP) and the percentage of hypochromic erythrocytes in patients with advanced acquired immunodeficiency syndrome (AIDS) treated with recombinant erythropoietin (rhEPO).. Patients received 150 IU rhEPO subcutaneously every second day for 10 days, and 150 IU rhEPO plus 62.5 mg of intravenous iron every second day for an additional 10 days.. Before rhEPO therapy, ZPP was at 64.3 +/- 27.3 micromol/mol heme and the percentage of hypochromic erythrocytes was elevated at 9.7%, indicating mild functional iron deficiency. Ferritin was 1,002 +/- 956 microg/L, with transferrin saturation of 19.1 +/- 9.7%. Under rhEPO alone, ZPP rose to 80.1 +/- 21.6 micromol/mol heme and the percentage of hypochromic red cells rose to 22.9 +/- 4.7%; ferritin fell to 705 +/- 601 microg/L and transferrin saturation fell to 12 +/- 6.3%. When rhEPO was supplemented with iron, ZPP fell to 70.4 +/- 20.5 micromol/mol heme, the percentage of hypochromic red cells fell to 14.7 +/- 3.4%; ferritin was unchanged at 771 +/- 62 microg/L and transferrin saturation rose to 20.5 +/- 5.5%.. In contrast to ferritin and transferrin saturation, ZPP and the percentage of hypochromic erythrocytes effectively detect the functional iron deficiency under rhEPO therapy in advanced AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Humans; Iron; Male; Metalloporphyrins; Middle Aged; Protoporphyrins; Recombinant Proteins; Severity of Illness Index

The transplantation of polymer encapsulated myoblasts genetically engineered to secrete erythropoietin (Epo) may obviate the need for repeated parenteral administration of recombinant Epo as a treatment for chronic renal failure, cancer or AIDS-associated anemia. To explore this possibility, the human and mouse Epo cDNAs under the control of the housekeeping mouse PGK-1 promoter were transfected into mouse C2C12 myoblasts, which can be terminally differentiated upon exposure to low serum-containing media. Pools releasing 150 IU human Epo per 10(6) cells per day and 390 IU mouse Epo per 10(6) cells per day were selected. Polyether-sulfone (PES) capsules loaded with approximately 200,000 transfected myoblasts from these pools were implanted on the dorsal flank of DBA/2J, C3H and C57BL/6 mice. With human Epo secreting capsules, only a transient increase in the hematocrit occurred in DBA/2J mice, whereas no significant response was detected in C3H or C57BL/6 mice. On the contrary, all mice implanted with capsules releasing mouse Epo increased their hematocrit over 85% as early as 7 days after implantation and sustained these levels for at least 80 days. All retrieved implants released Epo and contained well preserved myoblasts. Moreover most capsules were surrounded by a neovascularization. Mice transplanted with nonencapsulated C2C12 cells releasing mouse Epo showed only a transitory elevation of their hematocrit reflecting the poor engraftment of injected myoblasts. These results indicate that polymer encapsulation of genetically engineered myoblasts is a promising approach for the long-term delivery of bioactive molecules, allowing the resolution of the shortcomings of free myoblast transfer.

Topics: Acquired Immunodeficiency Syndrome; Analysis of Variance; Anemia; Animals; Antibodies, Monoclonal; Capsules; Cell Line; Erythropoietin; Female; Genetic Engineering; Genetic Therapy; Genetic Vectors; Hematocrit; Humans; Injections, Intramuscular; Kidney Failure, Chronic; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Muscle, Skeletal; Neoplasms; Time Factors; Transfection

The underlying theme of the 12th World AIDS Conference in Geneva was that while significant progress has been made in fighting the epidemic worldwide, there are still areas in which the disease is spreading and infection rates are increasing. Some have estimated that 40 million individuals in the developing countries may be infected by the year 2000. The conference was attended by 13,000 people who were briefed on vaccine development, current treatment regimens, promising drugs under development or in testing, treatment of opportunistic infections, advances in understanding and treating AIDS-related dementia, and policy issues.

Topics: Acquired Immunodeficiency Syndrome; AIDS Dementia Complex; AIDS Vaccines; Anemia; Anti-HIV Agents; Drug Therapy, Combination; Erythropoietin; Female; Humans; Male; Recombinant Proteins; Research; Switzerland; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia, Aplastic; Antineoplastic Agents; Erythropoietin; Hematopoietic Cell Growth Factors; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neutropenia; Transplantation

Similar to other lymphoid organs, the bone marrow (BM) is a potential reservoir for HIV-1. Although hematologic abnormalities are common in AIDS patients, the mechanisms by which HIV-1 contributes to these abnormalities are poorly understood. Hemapoietic suppression can be mediated by HIV-1 and some of its associated proteins. We have previously reported that AIDS peripheral blood sera inhibit normal CFU-granulocyte macrophage (GM). In this study, we have found that sera obtained from AIDS BM patients are more inhibitory to CFU-GM than those from peripheral blood (p < 0.05). To determine a candidate suppressor factor, we studied the role of p24 and found that it exerts varying degrees of suppression to CFU-GM, but minimal inhibition on erythroid colonies. We have found that the suppressive levels of p24 in in vitro assays are similar to the average circulating levels in AIDS patients. We have also observed that most of the inhibition caused by p24 is mediated by soluble factor(s) produced by the BM stroma. Cross-linking studies with membrane proteins from normal BM stroma and CD34+ cells indicated a putative 26-kDa p24 receptor, indicating that p24 binds to a receptor present on normal BM cells. These results implicate another HIV-1 protein, p24, in hemapoietic suppression and add another plausible mechanism by which HIV-1 contributes to BM failure in AIDS. Furthermore, these findings suggest a potential risk for similar in vivo suppression in the early phase of HIV-1 infection when viremia is elevated, and also in long-term survivors who have low, although persistent, HIV-1 replication.

Topics: Acquired Immunodeficiency Syndrome; Adipose Tissue; Bone Marrow; Bone Marrow Diseases; Cells, Cultured; Colony-Forming Units Assay; Connective Tissue; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; HIV Core Protein p24; HIV-1; Humans; Immunoglobulin G; Interleukin-3; Recombinant Proteins

A 35-year-old man from Central America with a history of AIDS and numerous opportunistic infections presented with progressive neutropenia and thrombocytopenia despite having been stable for a period of 6 months. Cessation of antiviral medications did not stop his neutropenia, nor did use of folinic acid, G-CSF, or erythropoietin. The failure of these measures required repeated blood transfusions. Although the physical examination was relatively unremarkable, hematology and blood chemistries indicated that the patient needed urgent hospitalization due to fever and neutropenia. Neutropenia within HIV infection can be confusing, since it may be a result of the infection itself, an adverse effect of drug therapy, or from an opportunistic infection or malignancy. If the cause is not evident, it is wise to seek the etiology first rather than immediately use bone marrow stimulants, such as G-CSF. In this case, an infectious disease specialist made a diagnosis of disseminated histoplasmosis, after which the patient was treated with amphotericin B and released on itraconazole maintenance therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Histoplasmosis; Humans; Male; Mucous Membrane; Neutropenia

Topics: Acquired Immunodeficiency Syndrome; Aluminum; Anemia; Drug Resistance; Erythropoietin; Humans; Hyperparathyroidism; Iron; Kidney Transplantation; Uremia

Topics: Acquired Immunodeficiency Syndrome; Anemia; Drug Resistance; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Treatment with zidovudine has been standard therapy for patients with advanced HIV infection, but intolerance is common. Previously, management of intolerance has consisted of symptomatic therapy, dose interruption/discontinuation, and, when appropriate, transfusion. The availability of new antiretroviral agents such as didanosine as well as adjunctive recombinant hematopoietic growth factors makes additional strategies possible for the zidovudine-intolerant patient. Because all of these agents are costly, we evaluated the cost implications of these various strategies for the management of zidovudine-intolerant individuals within a population of persons with advanced HIV disease. We performed a decision analysis using iterative algorithmic models of 1 year of antiretroviral care under various strategies. The real costs providing antiretroviral therapy were estimated by deflating medical center charges by specific Medi-Cal (Medicaid) charge-to-payment ratios. Clinical data were extracted from the medical literature, product package inserts, investigator updates, and personal communications. Sensitivity analysis was used to test the effect of error in the estimation of parameters. The models predict that a strategy of dose interruption and transfusion for zidovudine intolerance will provide an average of 46 weeks of therapy per year to the average patient at a cost of $5,555/year of therapy provided (1991 U.S. dollars). The models predict that a strategy of adding hematopoietic growth factors to the regimen of appropriate patients would increase the average amount of therapy provided to the average patient by 3 weeks (6%) and the costs attributable to therapy by 77% to $9,805/year of therapy provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Agranulocytosis; Algorithms; Anemia; Costs and Cost Analysis; Decision Support Techniques; Didanosine; Erythrocyte Transfusion; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Pancreatitis; Quality of Life; Zidovudine

The most common hematological abnormality associated with HIV infection is anaemia. The aetiology is multifactorial and may include the HIV virus itself; the anaemia of chronic diseases (ACD); infection with other viruses, mycobacteria and fungi; medications, especially zidovudine; and even B12 deficiency. Erythropoietin insufficiency is present in all anaemic AIDS patients, probably as a result of the mechanism of ACD. The studies, performed in patients with PGL, ARC and AIDS stages of disease demonstrate that rHuEPO is safe, and in dose of 100-200 U/kg b.w. three times a week can alleviate the anemia in AIDS patients taking AZT whose baseline EPO levels are less than 500 mU/ml.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Chronic Disease; Erythropoietin; Humans; Zidovudine

Use of the anti-viral drug zidovudine in the treatment of acquired immunodeficiency syndrome (AIDS) has been associated with the development of hematopoietic toxicity. Several hematopoietic growth factors have been investigated in their ability to modulate such toxicity; however, no single factor has been demonstrated to produce restoration of hematopoiesis following use with zidovudine. We report results describing the effect of combination interleukin-1 (IL-1) and erythropoietin (Epo) in their ability to modulate the hematopoietic toxicity associated with dose-escalation zidovudine administered in normal mice. When administered over a six-week period, IL-1 and Epo raised the packed red cell volume, white blood cell and platelet counts in control mice and mice receiving dose-escalation zidovudine. These effects were attributed in part to the ability of combination IL-1 and Epo to increase erythroid, myeloid and megakaryocyte progenitor stem cells from bone marrow and spleen. These results indicate that use of combined IL-1 and Epo may be efficacious in ameliorating the hematopoietic toxicity associated with the use of zidovudine.

Topics: Acquired Immunodeficiency Syndrome; Analysis of Variance; Animals; Bone Marrow; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Drug Interactions; Erythropoietin; Female; Hematocrit; Hematopoiesis; Hematopoietic Stem Cells; Humans; Interleukin-1; Leukocyte Count; Mice; Mice, Inbred C57BL; Platelet Count; Spleen; Time Factors; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Autoimmune Diseases; Blood Donors; Erythropoietin; Hematologic Diseases; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Cost-Benefit Analysis; Erythropoietin; Humans

Topics: Acquired Immunodeficiency Syndrome; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematocrit; Hematologic Diseases; Humans; Leukocyte Count; Lymphoma, AIDS-Related; Neutrophils; Recombinant Proteins

Epoetin (recombinant human erythropoietin) therapy for patients with AIDS may reduce the need for blood transfusion; however, it is expensive. We conducted a cost-effectiveness analysis of the use of epoetin for AIDS patients from a healthcare system perspective. We constructed a decision analysis model using probability, outcome and cost data from the literature and hospital sources. The incremental cost-effectiveness ratio was measured in dollars per unit of blood saved. In AIDS patients undergoing transfusion with serum epoetin concentrations less than or equal to 500 U/L treatment with epoetin cost $US1007 per unit of blood saved compared with treatment without epoetin. One-way sensitivity analysis revealed that the incremental cost-effectiveness ratio was sensitive to the efficacy and unit price of epoetin, but less sensitive to the current price cap determined by the distributor.

Topics: Acquired Immunodeficiency Syndrome; Cost-Benefit Analysis; Decision Trees; Drug Costs; Erythropoietin; Humans

Topics: Acquired Immunodeficiency Syndrome; Arthritis, Rheumatoid; Erythropoietin; Forecasting; Humans; Neoplasms; Postoperative Care

This study attempts to evaluate the adequacy of the erythropoietin (EPO) response in 42 anaemic patients with advanced human immunodeficiency virus (HIV) infection [30 with acquired immunodeficiency syndrome (AIDS) and 12 with AIDS-related conditions] by comparing their serum EPO levels with those found in a non-HIV reference population consisting of 36 patients with anaemia of chronic disorders (ACD) and 57 with iron deficiency anaemia (IDA). Although the average Hb concentration was similar in the three groups, the EPO level for HIV patients (mean +/- SEM, 64.3 +/- 7.7 mU/ml) did not differ significantly from that in ACD patients (45.3 +/- 8.3 mU/ml, P > 0.1), and both groups had a lower mean EPO level (P < 0.05 and P < 0.01 respectively) than IDA subjects (133.5 +/- 18.7 mU/ml). Thirteen HIV patients on zidovudine therapy showed similar mean Hb and EPO levels to those in the untreated patients. A significant inverse correlation between the log of serum EPO and the Hb values was observed in the three groups. However, this relationship was found to be stronger in IDA patients than in either HIV or ACD subjects (P < 0.001), with no difference between the two latter groups (P > 0.2). These data suggest that the EPO response is blunted in the anaemia associated with advanced HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acute-Phase Reaction; Adolescent; Adult; Aged; Anemia; Anemia, Hypochromic; Child; Chronic Disease; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Male; Middle Aged

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Blood Transfusion, Autologous; Erythropoietin; Evaluation Studies as Topic; Female; Hematocrit; Hemodilution; Humans; Intraoperative Care; Preoperative Care; Recombinant Proteins; Scoliosis

The pathophysiology of anemia in patients with human immunodeficiency virus (HIV) infection is multifactorial. In order to determine the role of erythropoietin (EPO) response as a cause of the anemia, serum levels were determined by direct radioimmunoassay in 110 symptomatic patients with various stages of HIV infection. Symptomatic patients (ARC and AIDS) not receiving zidovudine (ZDV) therapy demonstrated a strong inverse relationship between serum EPO and hemoglobin levels (p = 0.01 and p less than 0.001, respectively). Patients with AIDS who were anemic while receiving ZDV demonstrated serum EPO levels that ranged from normal to markedly elevated (9-3,390 mU/ml). The diversity of serum EPO levels in patients with HIV infection and anemia suggests that the etiology of anemia in these patients and their potential response to recombinant human EPO may not be uniform.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; Anemia; CD4-Positive T-Lymphocytes; Erythropoietin; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Zidovudine

Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex and multilineage hematopoietic defects were treated with recombinant granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) in a phase I/II trial. All patients were neutropenic and anemic after withdrawal of all bone marrow-suppressive drugs. Daily, G-CSF was subcutaneously self-administered until an absolute neutrophil count (ANC) greater than 6,000/microL was achieved and maintained for 2 weeks. Subcutaneous EPO was added to the regimen and the dose increased until an increase of 15 g/L of hemoglobin was observed. Groups of patients were administered increasing doses of zidovudine to determine their tolerance. G-CSF and EPO therapy was continued with dose modification to maintain an ANC greater than 1,500/microL and hemoglobin greater than 100 g/L. The dose of zidovudine was not altered. All 22 patients responded to G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2 weeks. Significant increases in CD4 and CD8 cell number, lymphocyte proliferative response, and bone marrow cellularity were seen. EPO therapy increased hemoglobin in all 20 evaluable patients within 8 weeks. Sixteen patients received 1,000 mg and four patients received 1,500 mg of zidovudine per day. The reinstitution of zidovudine resulted in a decline in reticulocytes and hemoglobin and the reappearance of transfusion requirements in eight of the 20 patients, six of whom had the study medications stopped. No patient had the study medications stopped because of neutropenia or thrombocytopenia. Toxicities were mild and did not require dose modifications. Limiting dilution plasma and lymphocyte co-cultures for HIV as well as serum p24 antigen levels did not change significantly during G-CSF or combined G-CSF and EPO therapy. HIV p24 antigen decreased significantly with zidovudine therapy. Opportunistic infections occurred in 14 patients but were successfully treated with myelosuppressive antimicrobial agents, including ganciclovir, without the development of neutropenia. These results suggest that combined therapy with G-CSF and EPO may improve the neutropenia and anemia of AIDS. Combined therapy may allow the resumption of full-dose zidovudine in most patients intolerant of the hematologic effects of zidovudine without apparent alteration of HIV expression or the efficacy of zidovudine.

Topics: Acquired Immunodeficiency Syndrome; Blood Cell Count; Cell Survival; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy, Combination; Erythropoietin; Ganciclovir; Gene Products, gag; Granulocyte Colony-Stimulating Factor; Hemoglobins; HIV; HIV Core Protein p24; Humans; Injections, Subcutaneous; Neutropenia; Opportunistic Infections; Recombinant Proteins; Viral Core Proteins; Virus Replication; Zidovudine

Hematopoietic dysfunction with peripheral cytopenias is a common complication of human immunodeficiency virus (HIV) infection. Symptomatic anemia is the most common cytopenia and occurs in the presence and absence of myelosuppressive drug therapy such as zidovudine. Drug-induced neutropenia and immune thrombocytopenia are also frequent and occur in up to 50% of acquired immunodeficiency syndrome (AIDS) patients. Attempts to reduce the impact of bone marrow failure have focused on dose reduction of zidovudine, ganciclovir, and chemotherapy, and the use of recombinant hematopoietic hormones such as erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF). Despite these maneuvers, approximately 30% of patients with AIDS receiving zidovudine will become transfusion-dependent. This has led to investigations of other cytokines that may increase blood cell formation. The recent identification of decreased number and proliferation of hematopoietic progenitors in patients with HIV infection suggests that agents which have activity on progenitor cell pools may have clinical utility. We demonstrate that human stem cell factor (HuSCF) increases burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte-monocyte (CFU-GM), and CFU-Mix formation in vitro in normal and HIV-infected individuals. HuSCF also decreases the sensitivity of BFU-E to inhibition by zidovudine without altering HIV replication in lymphocytes or monocytes, altering peripheral blood mononuclear cell proliferation to phytohemagglutinin (PHA) and interleukin-2 (IL-2) or altering the effectiveness of zidovudine or dideoxyinosine in inhibiting HIV replication in lymphocytes or monocytes. These studies suggest that HuSCF may have clinical utility in HIV infection as an adjunctive treatment for HIV-related cytopenias.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Anemia; Colony-Forming Units Assay; Erythroid Precursor Cells; Erythropoietin; Granulocytes; Hematopoietic Cell Growth Factors; HIV; HIV Infections; Humans; Lymphocytes; Macrophages; Monocytes; Neutropenia; Recombinant Proteins; Stem Cell Factor; Thrombocytopenia; Virus Replication; Zidovudine

The ability of peripheral-blood hematopoietic progenitor cells from AIDS patients and normal controls to respond to erythropoietin (Epo) was assessed for burst-forming units-erythroid (BFU-E). BFU-E colony formation from AIDS patients' peripheral blood responded to a wide range of Epo concentrations (0.5-4 U) in a similar manner as erythroid progenitors obtained from normal peripheral blood. The optimum dose response of BFU-E to Epo was 2 U which resulted in generation of 71 +/- 4 BFU-E in AIDS patients (n = 10), as compared to 77 +/- 5 BFU-E in normal donors (n = 3). The optimum concentration range of hemin enhancement of erythroid progenitor BFU-E was 10-50 microM. In all instances, Epo was essential for BFU-E growth. Inclusion of hemin at a concentration of 10 microM in AIDS patients' peripheral-blood erythroid progenitor cells resulted in enhancement of BFU-E by 136-215%. Similarly, inclusion of hemin (10-100 microM) in normal bone marrow erythroid progenitor cell cultures resulted in enhancement of BFU-E. Inclusion of an equivalent amount of iron or tin protoporphyrin to progenitors cells from AIDS patients' peripheral blood had no effect on the number of colonies observed. On the other hand, inclusion of another heme analogue, zinc protoporphyrin, in AIDS or normal cultures resulted in a 50% suppression of BFU-E colony formation. These results demonstrate that peripheral-blood mononuclear cells from AIDS patients retain the capacity to generate erythroid precursors such as BFU-E in the presence of Epo, and that hemin has a specific enhancement effect on growth of BFU-E colony formation obtained from peripheral blood or bone marrow cells.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; Cells, Cultured; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Drug Synergism; Erythroid Precursor Cells; Erythropoietin; Hemin; HIV Infections; Humans; Middle Aged; Opportunistic Infections; Protoporphyrins; Reference Values

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; United States; United States Food and Drug Administration; Zidovudine

Azidothymidine (AZT) induces severe anemia in patients with acquired immune deficiency syndrome (AIDS). To evaluate the mechanism of anemia in immune-suppressed animals, a murine model of AIDS (MAIDS), caused by infection with LP-BM5 murine leukemia virus (LP-BM5 MuLV) was used at early and late stages of the disease. AZT-induced anemia was dose- and time-dependent. An increased percentage of erythroblasts in bone marrow was observed, with an increased ratio of early to late erythroblasts in both disease stages. Increases in splenic erythroid burst-forming units (BFUe) were observed in early-stage AZT-treated mice. Mean plasma erythropoietin (EPO) levels were increased by AZT in both groups in a dose-dependent manner and were inversely proportional to hematocrit values. These data suggest that the anemia induced by AZT stimulated a response by immature erythroid elements, but that the maturation or survival of early erythroblasts may be impaired.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Animals; Bone Marrow; Disease Models, Animal; Dose-Response Relationship, Drug; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Hematocrit; Mice; Mice, Inbred C57BL; Pregnancy; Reticulocytes; Time Factors; Zidovudine

Zidovudine is now used extensively in an effort to control infection with the human immunodeficiency virus (HIV). The drug is associated with major hematologic toxicity, especially anemia and granulocytopenia. Conservative management of hematologic toxicity includes dosage reduction or cessation of therapy, diagnosis and treatment of chronic debilitating diseases, and supportive care, such as blood transfusions. New investigational agents, including hematopoietic growth factors, are being studied to combat the toxicities associated with zidovudine. The efficacy of these agents has yet to be established. Recent advances in drug efficacy at reduced dosage and in combination therapy promise to permit use of zidovudine with markedly reduced toxicity.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Leukopenia; Recombinant Proteins; Zidovudine

Erythropoietin (EPO) is a major regulatory factor controlling red blood cell (RBC) production in humans. Although other humoral factors can alter the proliferation of committed early erythroid progenitors in vitro, no factor other than EPO has been clearly shown to induce proliferation of these cells in vivo. In a clinical trail of recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant EPO in patients with advanced human immunodeficiency virus (HIV) infection, we noted reticulocytosis and increases in hemoglobin when G-CSF was administered before the administration of EPO. Subsequent studies demonstrated a significant increase in circulating burst forming unit-erythron (BFU-E) during daily recombinant G-CSF therapy. This increase was both time- and dose-dependent. The magnitude of increase in BFU-E correlated with the magnitude of increase in neutrophils and was associated with a mean increase in reticulocytes of 32,363/microL and a significant increase in mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a significant increase in iron binding capacity and decreases in iron saturation and ferritin levels. In patients who were not recently transfused, there was an associated fall in endogenous erythropoietin levels. The increase in RBC production was most marked in patients who were severely anemic, transfusion-dependent, and who had elevated pretreatment EPO levels. There was no correlation between the increase in BFU-E and endogenous EPO levels or the time since last dose of zidovudine. The addition of recombinant EPO therapy three times weekly to patients did not result in further significant increases in BFU-E but did significantly increase hemoglobin. Our data suggest that recombinant G-CSF may be one of the hematopoietic factors that influences production of BFU-E and RBCs in humans.

Topics: Acquired Immunodeficiency Syndrome; Cell Count; Colony-Stimulating Factors; Erythrocytes; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Injections, Subcutaneous; Recombinant Proteins; Reticulocytes

We investigated the in vitro growth of circulating progenitors from mononuclear nonadherent cells (MNAC) and T-depleted MNAC (non-T-MNAC) in the peripheral blood (PB) of 20 human immunodeficiency virus type 1 (HIV-1) seropositive subjects, compared with 12 normal adult volunteers, in order to clarify whether the loss of hemopoietic progenitors described in the bone marrow (BM) of AIDS-related complex (ARC)/AIDS patients could occur in PB before the AIDS stage, only those patients at the early stages of the disease who had never undergone cytotoxic therapy were considered in the study. We found a significant reduction in the number of granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM; p less than 0.001), megakaryocytic progenitors (megakaryocyte colony-forming units, CFU-MK; p less than 0.001) and erythroid progenitors (erythroid burst-forming units, BFU-E; p less than 0.05) in non-T-MNAC cultures of PB from HIV-1 seropositive subjects compared with normal PB control cultures. Although most of our patients had an inverted CD4/CD8 ratio and a marked reduction in the absolute number of CD4+ cells, there was no correlation with the absolute number of CD4+ cells or with the CD4/CD8 ratio. The loss of hemopoietic progenitors in PB seemed to occur earlier than in BM, because the hemograms of the patients considered in the study were normal in most cases.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; CD4-Positive T-Lymphocytes; Cell Count; Colony-Forming Units Assay; Colony-Stimulating Factors; Erythroid Precursor Cells; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Growth Substances; Hematopoietic Stem Cells; HIV Seropositivity; HIV-1; Humans; Interleukin-3; Macrophages; Male; Megakaryocytes; Recombinant Proteins; T-Lymphocytes, Regulatory

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Recombinant Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Erythropoietin; Federal Government; Ganciclovir; Government; Government Regulation; Human Experimentation; Humans; Patient Care; Pharmaceutical Preparations; Social Control, Formal; United States; United States Food and Drug Administration

Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Neutropenia; Recombinant Proteins; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Recombinant Proteins

Serum immunoreactive erythropoietin (SIE) and hemoglobin levels were measured in 152 patients infected with the human immunodeficiency virus. Anemia was present in 18% of asymptomatic patients who tested positive for the human immunodeficiency virus, 50% of patients with a condition related to the acquired immunodeficiency syndrome (AIDS), and 75% of patients with AIDS. The mean SIE level for untreated AIDS patients (26.2 +/- 2.4 mU/mL) was greater than for patients who tested positive for human immunodeficiency virus or patients with an AIDS-related condition but not outside the normal range for SIE (4 to 26 mU/mL), and the incremental increase in SIE level for a given decline in hemoglobin level was much less in AIDS patients than in patients with uncomplicated iron deficiency anemia. Forty-two patients were treated with zidovudine, and the hemoglobin level fell 10 g/L or more in 48%. In contrast to the untreated patients, however, the mean SIE level rose 10-fold to 214 mU/mL, and the incremental change in SIE level for a given decline in hemoglobin level was markedly increased. In the zidovudine-treated patients, erythrocyte mean corpuscular volume also rose significantly from a mean of 88.1 fL to 102 fL. However, in only 1 patient was there a corresponding increase in reticulocytes and in none was there amelioration of anemia. The data indicate that SIE level is inappropriately low in anemic AIDS patients. The ability of these patients to produce erythropoietin is intact and can be expressed with zidovudine therapy. However, even very high levels of SIE fail to stimulate erythropoiesis adequately.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Complex; Anemia; Blood Cell Count; Erythropoietin; Female; Hemoglobins; HIV Seropositivity; Humans; Longitudinal Studies; Male; Radioimmunoassay; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Anemia; Biological Products; Erythropoietin; Humans; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Erythropoietin; Ganciclovir; HIV-2; Humans; New York City

Topics: Acquired Immunodeficiency Syndrome; Clinical Protocols; Drugs, Investigational; Erythropoietin; Humans

The accurate radioimmunological measurement of serum erythropoietin (EPO) levels has only been possible since the development of highly specific antibodies directed against recombinant human EPO. In the present study, we determined the serum EPO levels in 100 healthy volunteers and in over 300 patients with anemias and hyperglobulinemia of various causes. In the healthy group, the females had levels of 11.3 +/- 3.4 mU/ml, while the males had levels of 8 +/- 3.2 mU/ml. The serum EPO concentrations were inversely related to the degree of anemia in patients with nonrenal anemias, while predialysis patients with renal anemias showed only partially such a tendency. Hemodialysis patients exhibited EPO-levels that were inadequately low relative to the degree of anemia. Patients with hyperglobulinemia had significantly higher serum EPO-levels than healthy individuals and polycythemia vera patients, the latter having particularly low serum EPO levels. Our results show that the determination of serum EPO levels can be of value in the differential diagnosis of hyperglobulinemia. Finally, sequential measurements document fluctuating serum EPO-levels after gastrointestinal hemorrhages and in patients with iron deficiency anemias receiving iron substitution. The probable reason for this phenomenon seems to be the intermittent utilisation of the hormone by EPO-sensitive erythropoietic precursor cells.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Anemia, Hypochromic; Erythropoietin; Female; Gastrointestinal Diseases; Hemoglobins; Humans; Hypergammaglobulinemia; Kidney Diseases; Male; Myelodysplastic Syndromes; Polycythemia Vera; Renal Dialysis