losartan-potassium and HIV-Infections

Recombinant human erythropoietin (rHuEpo) has become the most widely used cytokine in the world. Following the success of its use in patients with end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias was assessed, including pediatric patients and newborn infants. The treatment or prevention of anemia of prematurity with rHuEpo resulted in a significant reduction in the number of transfusions and donor exposure. A clear definition of which premature babies must receive therapy needs yet to be established. Other indications in neonatal period include hyporegenerative and hemolytic anemias. With the exception of chronic renal failure, in older children the efficacy of rHuEpo has not been evaluated as in adults. While an impressive amount of studies were carried out during the last years in adult patients with cancer-related or HIV-infection-related anemias, allowing to establish clear conclusions on its efficacy, only a few trials with small number of patients have been reported in children. Up to date, results in pediatric patients suggest that rHuEpo therapy is as useful as in adult patients, but prospective, randomized trials including large number of patients are essential to achieve definitive conclusions. Results of studies designed to evaluate the efficacy of rHuEpo for sustaining an adequate dose of ribavirin in patients receiving treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic effects of rHuEpo in newborn infants is a novel and exciting issue. The role of rHuEpo as a tissue protective factor for central nervous system and intestinal mucosa is under exhaustive investigation.

Topics: Adult; Anemia; Anemia, Neonatal; Child; Child, Preschool; Erythropoietin; Hepatitis C; HIV Infections; Humans; Infant; Infant, Newborn; Infant, Postmature; Neoplasms; Recombinant Proteins; Renal Dialysis; Renal Insufficiency

Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant. Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response. Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.

Topics: Algorithms; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Quality of Life; Recombinant Proteins; Ribavirin

Preoperative autologous blood donation (PABD) with no risk of blood-borne infection transmission has been considered the supreme blood transfusion therapy, and it has been reported to decrease incidence of postoperative deep-vein thrombosis. However, the need for PABD has decreased in the USA, because 1) risk of blood-borne infection transmission through allogeneic blood transfusion (ABT) has decreased after introduction of nucleic acid amplification test (NAT), and 2) blood collection-induced anemia has been found in many cases due to inapplicability of erythropoietin (rEPO). ABT risks are decreasing in Japan as in the USA, however, ABT has several issues proper to Japan, such as, outpacing of blood demand over supply in the near future and increase of HIV positive donors. Also, as rEPO can be used in Japan, PABD-induced anemia risks are low. Accordingly, necessity of PABD should increase in Japan. However, as those who usually perform PABD in Japan are surgeons, big issues arise such as bacterial contamination during blood collection and ABO incompatibility during transfusion. Underutilization of PABD in gastrointestinal cancer surgery should also be addressed. Appropriate technique and methodology must be established to increase the safety of PABD and to spread PABD in cancer surgery.

Topics: Anemia; Blood Donors; Blood Group Incompatibility; Blood Transfusion, Autologous; Cost-Benefit Analysis; Erythropoietin; HIV Infections; Humans; Japan; Medical Errors; Postoperative Complications; Preoperative Care; Recombinant Proteins; Safety; Venous Thrombosis

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

In patients with human immunodeficiency virus (HIV), anemia is a commonly encountered hematologic abnormality that has a significant impact on clinical outcomes and quality of life (QOL). This review describes the prevalence of anemia in several populations of patients with HIV and the effects of anemia on survival, morbidity, disease progression, transfusion requirements, and QOL. The prevalence of anemia in HIV disease varies considerably, ranging from 1.3% to 95%: it depends on several factors, including the stage of HIV disease, sex, age, pregnancy status, and injection-drug use as well as the definition of anemia used. In general, as HIV disease progresses, the prevalence and severity of anemia increase. Anemia is also more prevalent in HIV-positive women, children, and injection-drug users than in HIV-negative women, children, and injection-drug users. Anemia has been shown to be a statistically significant predictor of progression to the acquired immunodeficiency syndrome and is independently associated with an increased risk of death in patients with HIV. Treatment of anemia with epoetin-alpha has resulted in significantly fewer patients requiring transfusion as well as decreases in the mean number of units of blood transfused. Resolution of HIV-related anemia has been shown to improve QOL, physical functioning, energy, and fatigue in individuals with HIV. More recently, the use of highly active antiretroviral therapy has also been associated with a significant increase in hemoglobin concentrations and a decrease in the prevalence of anemia.

Topics: Activities of Daily Living; Adult; Anemia; Anti-HIV Agents; Blood Transfusion; CD4 Lymphocyte Count; Child; Comorbidity; Disease Progression; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; HIV Infections; Humans; Infant; Male; Outcome Assessment, Health Care; Pregnancy; Prevalence; Quality of Life; Recombinant Proteins; Severity of Illness Index; Substance Abuse, Intravenous; Survival Analysis

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.

Topics: Adult; Anemia; Anemia, Neonatal; Blood Transfusion, Autologous; Child; Clinical Trials as Topic; Erythropoietin; Female; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Male; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Despite the availability of highly active antiretroviral therapy and the resulting reduction in severe anemia associated with HIV infection, epoetin alfa has continued to play an important role in the management of HIV-infected patients. Mild-to-moderate anemia remains common, and its correction with epoetin alfa has resulted in significant improvements in quality of life, physical functioning, and possibly prolongation of survival. New research has demonstrated that epoetin alfa may have therapeutic potential beyond its ability to stimulate erythropoiesis due to its neuroprotective and antiapoptotic properties. Current and future research will further clarify the role of epoetin alfa in the clinical management of the HIV-infected population.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; HIV Infections; Humans; Recombinant Proteins; Treatment Outcome

Certain populations with chronic hepatitis C face special challenges in attaining optimal adherence to antiviral therapy, including patients coinfected with human immunodeficiency virus, patients undergoing dialysis for end-stage renal disease, and liver transplant recipients. These patient groups may stand to gain particular benefit from the expanding use of hematopoietic growth factors to manage the cytopenic effects of antiviral therapy for hepatitis C. This article reviews the rationale, current evidence, and future prospects for the adjunctive use of growth factors in these special populations with hepatitis C.

Topics: Anemia; Antiviral Agents; Clinical Trials as Topic; Comorbidity; Drug Therapy, Combination; Erythropoietin; Forecasting; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; HIV Infections; Humans; Interferons; Kidney Failure, Chronic; Liver Transplantation; Neutropenia; Patient Compliance; Recombinant Proteins; Recurrence; Renal Dialysis; Ribavirin

Anemia is a significant adverse effect of current hepatitis C treatment and may be a particular problem for HIV-infected patients, in whom there is a high prevalence of disease- or drug-related anemia at baseline. Hepatitis C treatment-induced anemia in HIV-HCV-coinfected patients can lead to ribavirin dose reduction or premature discontinuation of hepatitis C therapy, limiting sustained virologic response rates. Mean decreases in hemoglobin levels during hepatitis C treatment appear to be less in HIV-HCV-coinfected patients than in HCV-monoinfected patients, but any decrease in hemoglobin level may be more of a problem for coinfected patients. Thus, close monitoring of the hemoglobin level and appropriate management of the anemia that may develop in HIV-infected patients during hepatitis C therapy is essential.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

The oxygen-dependent, renal cytokine eythropoietin (Epo) is well known to increase red cell production. Binding of Epo to the Epo receptor (EpoR) represses apoptosis of erythroid progenitor cells, thereby allowing their final maturation. We and others showed that Epo and its receptor are expressed in many other tissues, including brain, spinal cord, retina and testis. The presence of a blood barrier suggests that Epo plays a local role in these organs. Indeed, therapeutically applied or hypoxically induced Epo has been shown to reduce the infarct volume in various stroke animal models, to prevent retinal degeneration, and to ameliorate spinal cord injury. In a study conducted by Ehrenreich and colleagues, stroke patients treated with Epo showed reduced infarct volume, fast neurological recovery and improved clinical outcome. In analogy to its function on erythroid progenitor cells, this neuroprotective effect of Epo might be explained by repression of programmed cell death. Apart from neuroprotection, there is an assumption that Epo present in breast milk has the potential to protect against mother-to-infant transmission of HIV. When using Epo at high doses for longer time periods; however, care has to be taken to control the resulting chronic polycythemia that most probably caused enlarged cerebral infarct volumes in a transgenic mouse model that due to Epo-overexpression reached hematocrit levels of about 0.8. Overall, these data strongly support the notion that Epo will soon find new applications in the clinic.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Injuries; Erythropoietin; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Ischemia; Male; Polycythemia; Pregnancy; Receptors, Erythropoietin; Recombinant Proteins; Retinal Vessels; Spinal Cord Ischemia; Stroke

Anemia management programs typically strive to maintain hemoglobin (Hb) levels in the target range of 11 to 12 g/dL recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Although nephrology clinicians are constantly alert for conditions that cause hyporesponse to Epoetin alfa therapy, management protocols generally focus on assessing and managing acute disorders that affect the production of red blood cells. A more difficult clinical challenge is how to systematically manage patients with conditions that chronically affect the erythropoietic response and are intractable to routine therapies. This article addresses the etiology and management of chronic conditions that require a specialized anemia management approach to ensure that patients can achieve targeted Hb levels and associated clinical and quality of life benefits. Examples include chronic inflammatory disorders, severe secondary hyperparathyroidism, malignancies, human immunodeficiency virus (HIV), and kidney transplant failure.

Topics: Aged; Anemia; Chronic Disease; Erythropoiesis; Erythropoietin; Female; HIV Infections; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neoplasms

Anemia is the most commonly encountered hematologic abnormality in human immunodeficiency virus (HIV)-positive patients, occurring with increasing frequency as the disease progresses. Several factors play a role in the development of anemia in patients with HIV, including chronic disease, opportunistic infections, and certain nutritional deficiencies. Despite the high prevalence of anemia in this population, the symptoms of anemia are frequently overlooked, although anemia can significantly affect a patient's ability to carry on even normal activities of daily living. Therefore, approaches--including the treatment of causative infections, discontinuation of certain drugs, or use of recombinant human erythropoietin (epoetin alfa)--aimed at increasing hemoglobin levels to normal or near-normal levels would be expected to improve quality of life (QOL). The purpose of this article is to describe the effects of anemia on QOL and to provide an overview of several studies showing that QOL improves with the alleviation of anemia.

Topics: Anemia; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Proteins; Ribavirin

Three large observational cohort studies suggest that, after controlling for virus load and CD4 cell count, anemia is related to disease progression and survival in patients with human immunodeficiency virus (HIV) infection. Recovery from anemia has been linked to improved survival outcomes. Blood transfusion has been associated with accelerated disease progression and mortality in patients with HIV infection, and review of related literature suggests that the mechanism for negative transfusion-associated outcomes may be transfusion-related immunosuppression. Therefore, the use of transfusion should be restricted to patients with acute or severe anemia. Prescription of epoetin alfa has been associated with increased survival in an observational cohort among patients with HIV infection and anemia. In the absence of data from a clinical trial documenting the effect of treating anemia on survival, clinicians should consider non-transfusion options for management of anemia on the basis of clinical status and patient functional ability.

Topics: Anemia; Blood Transfusion; Disease Progression; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; HIV Infections; Humans; Quality of Life; Recombinant Proteins; Survival Analysis

The recombinant human cytokines granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and interleukin-2 (IL-2) have been manufactured and licensed. Studies have been carried out that investigate the use of G-CSF and GM-CSF to reverse leukopenia, as adjunctive therapy for HIV-associated infections and for novel approaches to treat HIV infection, including stem cell mobilization. In addition, studies that identified the role of erythropoietin in the management of anemia have been performed. Furthermore, the abilities of G-CSF and erythropoietin to permit the continued use of marrow suppressive agents that are key in managing HIV infection have been assessed. The aim of this review is to summarize these studies and to describe the reports that evaluate the use of IL-2 to enhance elevation of CD4 cell counts mediated by highly active antiretroviral therapy. This summary is important to the treating clinician in that it identifies the optimal use of these cytokines in current clinical practice as well as their potential future roles.

Topics: Anemia; Colony-Stimulating Factors; Erythropoietin; HIV Infections; Humans; Interleukin-2; Neutropenia; Recombinant Proteins

Anemia, a common complication of HIV infection, is associated with morbidity and shortened survival. HIV-associated anemia can often be corrected with erythropoietin (EPO) therapy, which is safer than blood transfusion. Because the response to erythropoietin may be impaired by a number of treatable factors, all HIV patients with anemia should undergo careful evaluation for these factors. This article reviews evaluation and treatment strategies to maximize response to EPO and thus limit the need for blood transfusion.

Topics: Anemia; Erythropoietin; HIV Infections; Humans; Recombinant Proteins

The use of hematopoietic growth factors has increased rapidly during the last decade. Among the growth factors available, erythropoietin (EPO) was the first growth factor to be used clinically. To date, EPO has shown activity in the treatment of the tumor-associated anemia and for correction of tumor hypoxia, however, when compared with transfusion of erythrocytes EPO treatment did not significantly prolong survival in cancer patients in any published study so far. Recently, novel extramedullary EPO receptors have been identified leading to a better understanding of the molecular mechanisms of action of EPO. Results from these experiments and from several clinical studies suggest that EPO treatment may be beneficial for patients with (chronic) infections (HIV, inflammatory bowel disease, septic episodes) and for treatment of the fatigue syndrome following cancer chemotherapy. In addition, EPO may also improve stem cell engraftment following high-dose chemotherapy and can increase survival rates of patients with aplastic anemia and myelodysplastic syndrome. Currently, new EPO derivatives, synthetic fusion proteins and gene therapeutic studies are under clinical investigation suggesting that the EPO-induced effects may be increased significantly by these agents in the future.

Topics: Anemia, Aplastic; Chronic Disease; Erythropoietin; Fatigue; Genetic Therapy; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; HIV Infections; Humans; Infections; Myelodysplastic Syndromes; Receptors, Erythropoietin; Recombinant Proteins

Despite important advances in antiretroviral therapy, anemia remains a problem in many HIV-infected patients. Although the incidence of anemia in these patients has decreased, its prevalence appears to have stabilized or decreased only slightly. Anemia has a deleterious effect on both functional capacity and quality of life, and has been associated with shortened survival.. The Anemia in HIV Working Group, an expert panel of physicians and researchers involved in the care of HIV-infected patients, met to determine the impact of anemia in this patient population; to develop practice strategies for the clinician treating HIV-infected patients with anemia; and to identify future research directions.. The proposed practice strategies are based on results of the available clinical trials (as identified through a MEDLINE search), a review of the literature, and the clinical experience and expert opinion of the panel. The present report is based on meetings held in February and June of 1998; as further experience with various treatment options accumulates and the impact of highly active antiretroviral therapy becomes clearer, the panel will reconvene to develop evidence-based guidelines.. The working group considers HIV-associated anemia to be an important contributor to the morbidity and mortality of this infection. Recent reports indicate that recovery from anemia is associated with improved quality of life and survival.. As HIV-infected persons live longer, maintaining quality of life becomes an increasingly important goal of treatment. When planning treatment strategies, clinicians should consider the quality-of-life decrement caused by anemia. Transfusions should be used when rapid recovery is required, and underlying conditions causing anemia should be treated, if possible. Recombinant human erythropoietin (rHuEPO) therapy is appropriate in certain HIV-infected persons and should be considered to maintain hemoglobin concentrations. The target hemoglobin level is 12 g/dL for men and 11 g/dL for women. Weekly rHuEPO dosing is suggested, initiated at 40,000 U, as has been established in patients with cancer.

Topics: Anemia; Erythropoietin; Female; HIV Infections; Humans; Male; Practice Patterns, Physicians'; Quality of Life; Recombinant Proteins

Anemia, a common hematologic complication in human immunodeficiency virus (HIV)-infected patients, can be caused by mechanisms including infections, neoplasms, or drug treatment. Studies have consistently found anemia to be associated with reduced survival, even when potentially confounding factors were controlled for. Importantly, recovery from anemia has been shown to reduce this risk to approximately the same level as seen among patients never having had anemia. Although anemia traditionally has been treated with blood transfusions, recent studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in elevating hematocrit values and reducing transfusion requirements in HIV-infected patients who have endogenous erythropoietin levels of < or = 500 IU/L. Therapy with r-HuEPO has been shown to be safe and well tolerated. In a recent study, moreover, receipt of erythropoietin was associated with a decreased risk of death, whereas transfusion was associated with an increased risk. If these results are confirmed, the link between r-HuEPO and decreased risk of death in HIV-infected patients with anemia will be further strengthened.

Topics: Anemia; Blood Transfusion; Erythropoietin; HIV Infections; Humans; Recombinant Proteins; Risk Factors; Survivors

Topics: Blood Banks; Blood Loss, Surgical; Blood Transfusion, Autologous; Contraindications; Erythropoietin; HIV Infections; HIV Seropositivity; Humans; Medical Errors; Recombinant Proteins; Risk Assessment; Safety

Topics: Anemia; Anti-HIV Agents; Erythropoietin; HIV Infections; Humans; Recombinant Proteins; Time Factors; Zidovudine

Multilineage hematopoietic defects occur in patients with human immunodeficiency virus (HIV) infection and affect therapy of the disease and of associated opportunistic infections and neoplasms. Anemia and neutropenia are common in HIV patients, and can occur as a result of HIV-related myelosuppression or complications or may be secondary effects of antiretroviral or other agents used in management of the disease. With the advent of combination drug therapy for the treatment of HIV infection and prophylaxis and treatment of infectious complications, myelosuppression is frequently encountered and may be treated with synthetic hematopoietic growth factors. Erythropoietin has been shown to increase mean hematocrit levels and to reduce transfusion requirements in anemic HIV-infected patients receiving zidovudine. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor have been shown to increase neutrophil counts in patients with AIDS-related bone marrow failure and those receiving zidovudine, interferon-alpha, or ganciclovir. Although recent research using interleukin-2 (IL-2) has shown that use of this cytokine in AIDS patients can lead to increases in CD4 cell counts that appear to be functional, further study is needed to determine whether cytokines can play a role other than palliation in HIV-infected patients.

Topics: Cytokines; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Diseases; HIV; HIV Infections; Humans; Interleukin-2; Interleukin-3; Virus Replication

The anaemia that is a common complication of human immunodeficiency virus (HIV) infection bears many similarities to the anaemia of chronic disease. These similarities include an impaired erythropoietin (EPO) response to anaemia, reduced concentrations of marrow progenitors giving rise to erythroid colonies, abnormalities of reticuloendothelial iron metabolism, and correction of anaemia with recombinant human EPO. A model has been developed in which the pathophysiologic processes producing the anaemia of chronic disease may be attributed to actions of the cytokines that mediate the immune response, such as interleukin-1, tumor necrosis factor and the interferons. These cytokines are also implicated in HIV-related anaemia. In this review, the applicability of this cytokine-mediated anaemia model to the anaemia of HIV infection is explored.

Topics: Anemia; Cytokines; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; HIV Infections; Humans; Interferons; Interleukin-1; Iron; Tumor Necrosis Factor-alpha

During the course of HIV disease a broad spectrum of hematologic disorders develop including abnormalities in blood cell generation, survival, and function Alterations in coagulation parameters may evolve associated with disruption of immunoglobulin or factor production. This article reviews the manifestations and pathophysiology of these abnormalities and discusses the role for growth factor support.

Topics: Blood Coagulation Disorders; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Hematologic Diseases; HIV Infections; Humans; Lymphopenia

Neutropenia and anaemia are common problems in patients with HIV infection. Neutropenia can lead to a reduction in drug doses or to withdrawal of important myelosuppressive agents such as ganciclovir, zidovudine, cotrimoxazole and pyrimethamine, while anaemia may require the administration of blood transfusions.. Haematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are effective in the treatment of AIDS-related neutropenia. G-CSF appears to be better tolerated than GM-CSF. Moreover, GM-CSF can stimulate HIV replication in the absence of antiretroviral treatment. Thus G-CSF may offer a better treatment option in some patients. Doses of up to 300 micrograms G-CSF (filgrastim) per day rapidly reverse neutropenia in most HIV-infected patients. Subsequently, normal neutrophil counts can be maintained with intermittent doses (1-7 days a week). This allows greater use of myelosuppressive agents. Recombinant human erythropoietin is well tolerated and effective in the treatment of anaemia due to zidovudine when endogenous erythropoietin levels are < or = 500 IU/l. Recombinant human erythropoietin combined with CSF also appears to be well tolerated and effective in the treatment of combined cytopenias. Other haematopoietic growth factor combinations are currently being explored.. CSF and recombinant human erythropoietin, used alone or in combination, appear to be well tolerated and effective in the treatment of neutropenia and anaemia, respectively, in patients with HIV infection. G-CSF may be preferable to GM-CSF in some patients. However, the advantages of therapy with haematopoietic growth factors have to be balanced against the disadvantages of cost, inconvenience and discomfort associated with repeated subcutaneous injections. At present there is no clear evidence that CSF prolongs the survival of AIDS patients.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Filgrastim; Ganciclovir; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV Infections; Humans; Immunosuppression Therapy; Neutropenia; Recombinant Proteins

Recombinant human erythropoietin has been available for clinical use since 1985. It was an immediate success in treating the anemia of chronic renal failure and has also enjoyed some objective success in the treatment of other anemias in either a therapeutic or prophylactic setting, but the issues of appropriate patient selection and cost-benefit ratios are still unresolved. This review discusses the most recent literature concerning the use of recombinant human erythropoietin for the anemia associated with cancer, HIV infection, myelodysplasia, prematurity, autologous blood transfusion, bone marrow transplantation, and chronic renal failure.

Topics: Anemia; Blood Transfusion, Autologous; Erythropoietin; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

Human immunodeficiency virus infection causes multilineage hematopoietic defects. Defects in the production and function of CD4+ helper cells have been the focus of the majority of HIV research, but anemia, neutropenia, and thrombocytopenia are significant clinical problems as well. Bone marrow suppression is the dose-limiting toxicity for a number of antiviral and prophylactic medications. Hematopoietic growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor are used to optimize the delivery of antiretroviral and prophylactic therapy. Because of the expense involved, the most appropriate use of these hematopoietic growth factors remains a subject of intense investigation. This review focuses on recent experimental results.

Topics: AIDS-Related Opportunistic Infections; Bone Marrow Diseases; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Neutropenia; Virus Replication

Patients with HIV infection frequently develop clinically significant anemia, either as a manifestation of the HIV or as a result of therapy with medications such as zidovudine. Therapy with recombinant human erythropoietin can increase hemoglobin levels in these patients, decreasing transfusion requirements and improving some aspects of the quality of life. Once erythropoietin therapy is started, it is important to monitor patients carefully for the development of iron deficiency and erythrocytosis.

Topics: Anemia; Clinical Trials as Topic; Cost-Benefit Analysis; Erythropoietin; HIV Infections; Humans; Recombinant Proteins

Topics: AIDS-Related Opportunistic Infections; Anemia; Anemia, Hemolytic, Autoimmune; Antiviral Agents; Bone Marrow Diseases; Erythropoietin; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Knowledge continues to grow on the biology of endogenous erythropoietin (EPO), its effects on red blood cell physiology, and the use of the recombinant form of the hormone. In addition to oxygen delivery, oxygen consumption may be important in stimulating EPO production. This production is likely mediated by an intracellular messenger system other than cAMP. Once released, EPO prevents programmed cell death of BFU-E and CFU-E cells. Recent evidence suggests that lack of EPO, rather than the presence of EPO inhibitors, is the cause of the anemia seen in renal patients. Recombinant EPO has been available clinically since mid 1989. Nearly two thirds of dialysis patients are receiving this agent, although low doses are the rule, with the average hematocrit achieved of only 31%. EPO dosing has been subjected to kinetic modeling that has revealed a wide range in RBC half-life from patient to patient. This accounts in part for the varying maintenance dosing requirements. An additional modulating factor in the response to EPO is severe, secondary hyperparathyroidism with bone marrow fibrosis which may be reversible with medical or surgical parathyroidectomy. Hypertension continues to occur in 20-35% of patients given EPO. This effect may be mediated by endothelin which appears to be stimulated by EPO administration. Treatment of the anemia of renal failure leads to many organ system benefits including improved muscle metabolism, decreased left ventricular hypertrophy, enhanced immune responses to hepatitis vaccine, and improved brain electrophysiology. he optimal target hematocrit to achieve the greatest benefits for the patient at an acceptable cost remains to be determined.

Topics: Adult; Aged; Anemia; Child; Erythropoiesis; Erythropoietin; Female; Hematocrit; HIV Infections; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Pregnancy; Pregnancy Complications; Recombinant Proteins; Renal Dialysis

The human recombinant hematopoietic growth factors have attracted widespread interest because of their potential efficacy in a number of clinical settings. Recombinant human erythropoietin is now an established therapy to treat and prevent the anemia associated with chronic renal failure in children and adults. This agent also shows extraordinary promise to stimulate erythrocyte production and reduce transfusion requirements in premature infants. Granulocyte and granulocyte-macrophage colony-stimulating factors stimulate the production and function of myeloid cells and have provided major clinical benefit to children with congenital disorders of neutrophil production. The myeloid growth factors also show great promise in reducing the duration and severity of neutropenias associated with cytotoxic cancer treatment and in improving granulocyte production in patients with human immunodeficiency virus infections.

Topics: Anemia; Anemia, Aplastic; Antineoplastic Agents; Bone Marrow Transplantation; Child; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Infant, Newborn; Neutropenia; Recombinant Proteins; Stem Cell Factor

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

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

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Leukopenia; Zidovudine

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

Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard treatment for hepatitis C virus (HCV) infection, are frequently associated with neutropenia and anemia, leading to high treatment discontinuation rates in HIV/HCV-coinfected patients. Our objective was to compare the effectiveness of intervening with hematologic growth factors versus dose reductions of standard HCV therapy for the management of treatment-induced hematologic disorders.. Ninety-two HIV/HCV-coinfected, therapy-naive subjects received PEG-IFN alfa-2b 1.5 μg·kg⁻¹·wk⁻¹ and RBV 13 ± 2 mg·kg⁻¹·d⁻¹ for up to 48 weeks. Before treatment initiation, subjects were randomized to subsequently receive growth factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte colony-stimulating factor, or dose reduction (RBV and/or PEG-IFN) for anemia and neutropenia management, respectively. We analyzed the ability of each management strategy to control anemia and neutropenia and the percentage of subjects who achieved a successful treatment outcome according to the different management strategies.. During treatment, 43 subjects developed anemia (human erythropoietin, n = 24; dose reduction, n = 19), whereas 25 subjects developed neutropenia (granulocyte colony-stimulating factor, n = 10; dose reduction, n = 15). After the intervention, the increase in both hemoglobin and absolute neutrophil counts did not differ between the 2 side effect management strategies. Sustained response percentages were similar comparing anemic and neutropenic subjects regardless of management strategy (anemia: recombinant human erythropoietin, 29% versus dose reduction, 21%, P = 0.92; neutropenia: granulocyte colony-stimulating factor, 40% versus dose reduction, 20%, P = 0.46).. Growth factor supplementation and dose reduction do not seem to differ as management strategies for anemia and neutropenia in HIV/HCV-coinfected individuals treated with PEG-IFN/RBV.

Topics: Adult; Aged; Anemia; Antiviral Agents; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; HIV Infections; Humans; Intercellular Signaling Peptides and Proteins; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Multicenter Studies as Topic; Polyethylene Glycols; Recombinant Proteins; Ribavirin

Chronic hepatitis C affects one-third of HIV(+) patients worldwide. High ribavirin (RBV) exposure is crucial to maximize the response to hepatitis C therapy in this population, although it may increase the risk for hemolytic anemia. PERICO is a prospective multicenter trial in which HIV/HCV-coinfected patients are randomized to receive peginterferon (pegIFN) alfa-2a 180 microg/week plus either weight-based RBV (1000-1200 mg/day) or RBV 2000 mg/day, the latest along with erythropoietin alfa (EPO) 30,000 IU/week from the first day until week 4. A total of 149 patients were assessed in a planned interim analysis at week 4. In both arms, 22% of patients achieved negative HCV-RNA (rapid virological response, RVR). Multivariate analysis [OR (IC 95%), p] showed that factors associated with RVR were HCV genotypes 2/3 vs. 1/4 [20 (5-100), <0.01] and baseline HCV-RNA [0.16 (0.07-0.37) per log IU/ml, <0.01]. The occurrence of severe anemia (hemoglobin <10 g/dl) did not differ when comparing RBV vs. high RBV + EPO (7% vs. 3%; p = 0.4). Moreover, RBV plasma trough levels were comparable at week 4 (1.9 vs. 2.4 microg/ml; p = 0.2). Use of high RBV doses with preemptive EPO during the first 4 weeks of hepatitis C therapy is safe, but fails to enhance significantly RBV plasma exposure and RVR rates. Extensive intraerythrocyte accumulation of RBV following boosted production of red blood cells by EPO could explain these findings.

Topics: Adult; Anemia, Hemolytic; Antiviral Agents; Epoetin Alfa; Erythrocytes; Erythropoietin; Female; Hematinics; Hepacivirus; Hepatitis C, Chronic; HIV; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome

Anemia, a common hematological abnormality in HIV, contributes to decreased quality of life (QOL). This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin (Hb) in anemic HIV-infected patients in a 24-week, open-label, multicenter study. HIV-infected patients (Hb < or =12 g/dl) received epoetin alfa 40,000 units subcutaneously once weekly, until reaching Hb > or =13 g/dl. Patients then entered a maintenance phase (MP), in which epoetin alfa was administered every other week or at longer intervals. The trial objectives were to determine if QOL, as measured by the Medical Outcomes Study-HIV (MOS-HIV) general health perceptions (GHP) domain and Hb, was maintained. Safety was also assessed. A total of 292 patients were enrolled (72% on HAART). Mean baseline laboratory values were Hb = 10.8 g/dl, CD4(+) count = 280 cells/microl, and HIV RNA = 51,867 copies/ml. In all, 81% of patients reached Hb > or =13 g/dl and 92% reached Hb > or =12 g/dl. QOL was maintained from the beginning (GHP = 44.2 points) to the end of MP (GHP = 43.4 points) with every other week or longer dosing. Mean Hb at the beginning of MP was 13.4 +/- 0.5 g/dl and was 12.8 +/- 1.4 g/dl at study end. Epoetin alfa was well tolerated; adverse events were consistent with those reported in previous studies of epoetin alfa in HIV-infected patients. Although the clinical approach tested in this study is not consistent with current prescribing recommendations, the results confirm the efficacy of prolonged dosing intervals (every 2-4 weeks) in maintaining optimal Hb levels and QOL in anemic HIV-infected patients.

Topics: Adult; Aged; Anemia; CD4 Lymphocyte Count; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Injections, Subcutaneous; Male; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome; Viral Load

HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750 cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received filgrastim, and 12 (40%) received darbepoetin. Seven (23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients.

Topics: Adult; Antiviral Agents; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin

Topics: Adolescent; Adult; Aged; Anemia; Antiviral Agents; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hepatitis C; HIV Infections; Humans; Interferons; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin

This prospective, open-label, multicenter trial evaluated the effects of once-weekly (qw) epoetin alfa on quality of life (QOL) and hemoglobin (Hb) levels in anemic human immunodeficiency virus (HIV)-infected adult receiving antiretroviral therapy. A total of 650 patients with Hb < or = 11 g/dl received epoetin alfa 40,000 U qw subcutaneously, with dose escalation to 60,000 qw if Hb increase was <1 g/dl after 4 weeks. The linear Analog Scale Assessment (LASA) overall QOL score, LASA energy score, and LASA activity score each significantly improved from baseline to final measurement (p < 0.0001 for each parameter). Improvements in the Medical Outcomes Study (MOS)-HIV physical and mental health summary scores were also significant (p < 0.0001), and coincided with Hb increases. Mean Hb increased from baseline to final measurement by 2.5 g/dl (95% CI: 2.3, 2.6 g/dl; p < 0.0001). Objective hematological response rate, defined as a > or = 1 g/dl Hb increase from baseline to week 8, was 86%. Hemoglobin increased significantly in all subgroups of race, zidovudine use, CD4+ cell count, and viral load. Once-weekly epoetin alfa was well tolerated. Once-weekly epoetin alfa is effective in improving QOL and Hb measures.

Topics: Adult; Aged; Anemia; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia is prevalent in HIV-positive patients despite lower doses of zidovudine used in highly active antiretroviral therapy. Previously, epoetin alfa has been administered 3 times weekly (TIW). We compared the hematologic and quality of life (QOL) effects and tolerability of the more convenient once-weekly (QW) regimen with TIW epoetin alfa in anemic HIV-positive patients.. Two hundred eighty-five anemic (hemoglobin [Hb] <12 g/dL) HIV-positive adults receiving stable antiretroviral therapy were enrolled in this 16-week, randomized, multicenter study. Enrolled patients were randomized to receive epoetin alfa doses of 40,000 to 60,000 U QW or 100 to 300 U/kg TIW.. Two hundred seventy-two patients were evaluable for efficacy. Both epoetin alfa dosing schedules produced significant Hb level increases by week 2 (mean Hb increase of 1.3 g/dL [QW] and 1.0 g/dL [TIW]; P < 0.0001) that continued to increase until week 8 and were maintained until study completion, with no significant difference between treatment groups at final Hb measurement (mean Hb increase of 2.9 g/dL [QW] and 2.5 g/dL [TIW]). All QOL parameters improved significantly (P < 0.05) from baseline by week 8 in both groups, with no significant differences between groups at week 16. Both dosing schedules were well tolerated.. QW dosing of epoetin alfa is as effective as TIW dosing in increasing Hb levels, which was associated with improved QOL in anemic HIV-positive patients. QW dosing should also offer added convenience for patients and caregivers.

Topics: Adult; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; HIV-1; Humans; Male; Prospective Studies; Quality of Life; Recombinant Proteins

To evaluate the effect of epoetin alfa on the quality of life (QOL) of HIV-infected patients in the community setting, 221 anaemic (haemoglobin < or = 11 g/dl) HIV-positive patients from community-based treatment centres and physicians' offices were treated with epoetin alfa (100-300 units/kg subcutaneously 3 times a week) in a 4-month, open-label, non-randomized, phase IV trial. Epoetin alfa therapy significantly (P<0.01) increased and maintained haemoglobin levels (mean increase=2.5 g/dl; n=207); the improvement in haemoglobin levels was independent of changes in CD4+ cell counts. Transfusion requirements were also significantly reduced from 20% to 5% of patients (P<0.01). Mean total QOL score measured by the Functional Assessment of HIV Infection (FAHI) scale and Physical Well-Being subscale score improved significantly (P<0.05). QOL improvements associated with increases in haemoglobin were independent of changes in CD4+ counts and baseline anaemia severity. Adverse events observed during epoetin alfa therapy were consistent with HIV disease and not likely due to the drug. Epoetin alfa therapy should be considered a treatment option for HIV-infected patients with mild-to-moderate anaemia.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Male; Quality of Life; Recombinant Proteins

Topics: Adult; Anemia; Erythropoietin; Female; Hematocrit; Hemoglobins; HIV Infections; Humans; Longitudinal Studies; Male; Prospective Studies; Recombinant Proteins

Topics: Adolescent; Anemia; Child; Child, Preschool; Erythropoietin; Female; HIV Infections; Humans; Infant; Male; Recombinant Proteins

The aim of this randomized, comparative, double-blind study was to determine the efficacy of zidovudine (ZVD) either alone or in combination with recombinant granulocyte-colony stimulating factors (rG-CSF) and erythropoietin (Epo) in asymptomatic HIV-infected subjects with a CD4+ cell count < 500/mm3, classified as CDC II stage. We recruited 20 HIV Ab+ asymptomatic patients who were randomized into two groups: A and B. Group A was treated with ZVD at the dosage of 500 mg daily in combination with rG-CSF (10 micrograms/Kg/biweekly) and Epo (50 IU/Kg/biweekly). Group B was treated with ZVD (500 mg/day) alone. The primary end-point was progression to an AIDS-defining event and the secondary end-point included changes in the CD4+ cell count, p24 Ag status, beta-2-microglobulin, and ferritin levels. The patients of Group A showed no significant changes in transaminase, ferritin and beta-2-microglobulin levels while CD4 cells, Hb and neutrophil levels increased significantly compared to Group B (p < 0.001) and baseline values (p < 0.05). Conversely, 5 patients in Group B showed a significant decrease in CD4 cells (p < 0.01), Hb and neutrophil levels (p < 0.01) compared to baseline values, while beta-2-microglobulin increased (p < 0.05) compared to initial values. Our preliminary study may indicate that the combination of zidovudine with these hematopoietic growth factors could reduce the possibility of virus-related hematologic toxicity and could be more efficacious than zidovudine alone in prolonged therapy.

Topics: Adult; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Double-Blind Method; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; HIV Infections; HIV Seropositivity; Humans; Male; Recombinant Proteins; Reverse Transcriptase Inhibitors; 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

Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China.. This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann-Whitney U test, and chi-square statistics were applied in SPSS.. The Hgb of HIV-HD and HD groups were 105.70 (95.93-112.08) g/L and 112.00 (93.00-126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38-589.75) ng/ml and 272.70 (205.00-434.00) ng/ml in HIV-HD and HD groups respectively.. A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.

Topics: Adult; Anemia; China; Cross-Sectional Studies; Erythropoietin; Female; Ferritins; Hemoglobins; HIV Infections; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Serum Albumin

Anemia is the most common hematological abnormality in human immunodeficiency virus (HIV)-infected patients. Besides chronic disease, opportunistic infections, nutritional deficiencies and antiretroviral drug toxicity, the direct role of HIV in the development of anemia has not yet been fully investigated. To explore the HIV-related mechanisms involved in the genesis of anemia, we used two experimental designs. In the first, HPCs purified from cord blood were challenged with HIV-1IIIb or recombinant gp120 (rgp120) and then committed to erythrocyte differentiation (EPO-post-treated HPCs). In the second, HPCs were first committed to differentiate towards the erythroid lineage and only afterwards challenged with HIV-1IIIb or rgp120 (EPO-pre-treated HPCs). Our results showed that HPCs and EPO-induced HPCs were not susceptible to HIV-1 infection. In addition, the two experimental designs (EPO post or pre-treated HPCs) independently showed that HIV-1IIIb or rgp120 were able to induce the impairment of survival, proliferation, and differentiation albeit differing in kinetics and extent. Interestingly, the gp120 interaction with CD4 and CXCR4 played a pivotal role in the impairment of erythrocyte differentiation by inducing TGF-b1 expression. These observations reveal an important additional mechanism involved in the genesis of anemia suggesting a complex competition between EPO-positive regulation and HIV-negative priming regarding erythrocyte survival, proliferation and maturation.

Topics: Anemia; Antigens, CD34; CD4 Antigens; Cell Differentiation; Cell Proliferation; Cell Survival; Erythrocytes; Erythroid Cells; Erythropoietin; Fetal Blood; Gene Expression Regulation; Glycophorins; Hematopoietic Stem Cells; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Receptors, CXCR4; Recombinant Proteins

Hyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism.. We present the case of a 58-year-old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR).. The patient was ABO group B and had a previously identified anti-Fy(b) alloantibody. After transfusion of Fy(b)--RBCs, she developed a DHTR and was found to have anti-E, anti-C(w), anti-s, and an additional antibody to an unrecognized high-frequency RBC alloantigen. Subsequent transfusion of ABO-compatible RBCs that were negative for Fy(b), E, C(w), and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high-frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. The Hct and clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without a Hb disorder, the development of an antibody to an unknown RBC antigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion.. Hyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due to RBC alloantibodies remains uncertain.

Topics: Acute Disease; Adrenal Cortex Hormones; Anemia, Hemolytic; Antibodies, Monoclonal, Humanized; Blood Group Incompatibility; Cholecystitis; Coombs Test; Drug Resistance; Duffy Blood-Group System; Dyspnea; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Hepatitis C, Chronic; HIV Infections; Humans; Isoantibodies; Middle Aged; Oxygen Inhalation Therapy; Premedication; Pulmonary Disease, Chronic Obstructive; Receptors, Cell Surface; Syndrome; Transfusion Reaction

Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-α (IFN-α), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS) was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24), matrix (p17), envelope (gp41), and reverse transcriptase (RT) were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.

Topics: Antibody Formation; Autoantibodies; Demography; Erythropoietin; Female; HIV Infections; HLA-DR Antigens; Humans; Immunoglobulin lambda-Chains; Interferon-alpha; Interleukin-2; Male; Molecular Mimicry; Viral Proteins

The effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in 'real world', clinical practice is unclear.. To determine the rates and predictors of sustained virological response (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and ribavirin in HIV/HCV co-infected patients.. We identified all HIV/HCV co-infected patients who received anti-viral treatment with PEG-IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n = 665).. Sustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1 HCV (n = 491) and 44% among patients with genotype 2 or 3 HCV (n = 116). Among genotype 1-infected patients, characteristics that were negatively associated with SVR independently included baseline HCV viral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI 0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)], baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio ≥1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR 0.41 (0.2-0.9)]; characteristics positively associated with SVR included a starting dose of ribavirin ≥1000-1200 mg/day [AOR 2.0 (1.1-3.7)] and erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor of SVR [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800 mg/day was not associated with SVR.. Sustained virological response rates achieved with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated with SVR.

Topics: Antiviral Agents; CD4 Lymphocyte Count; Coinfection; Erythropoietin; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Interferon-alpha; Male; Middle Aged; Ribavirin; RNA, Viral; Treatment Outcome; Viral Load

Circulating autoantibodies to endogenous erythropoietin (anti-Epo) are detected in human immunodeficiency virus type 1 (HIV-1)-infected patients and represent a risk factor for anemia. The aim of this study was to map the B-cell epitopes on the Epo molecule.. Serum samples from HIV-1-positive patients and healthy individuals were tested against overlapping peptides covering the entire sequence of Epo.. Serum samples from anti-Epo-positive patients exhibited significant binding to Epo epitopes spanning the following sequences: amino acids 1-20 (Ep1), amino acids 54-72 (Ep5), and amino acids 147-166 (Ep12). Structural analysis of erythropoietin revealed that the immunodominant epitopes, Ep1 and Ep12, comprise the interaction interface with Epo receptor (EpoR). Autoantibodies binding to this specific region are anticipated to inhibit the Epo-EpoR interaction, resulting in blunted erythropoiesis; this phenomenon is indicated by the significantly higher Epo levels and lower hemoglobin levels of anti-Ep1-positive patients compared with anti-Ep1-negative individuals. The region corresponding to the Ep1 epitope exhibited a 63% sequence homology with the ³⁴LVCASRELERFAVNPGLLE⁵² fragment of the HIV-1 p17 matrix protein.. These results suggest that the main body of anti-Epo is directed against a functional domain of Epo, and that the presence of anti-Epo can be considered to be a result of a molecular mimicry mechanism, which is caused by the similarity between the Ep1 region and the p17 protein.

Topics: Adult; Anemia; Epitope Mapping; Epitopes, B-Lymphocyte; Erythropoietin; Female; gag Gene Products, Human Immunodeficiency Virus; HIV Antigens; HIV Infections; HIV-1; Humans; Male; Middle Aged; Molecular Mimicry

In a previous retrospective study we have shown that circulating antibodies to endogenous erythropoietin (anti-EPO) are associated with HIV-1-related anemia. The present longitudinal cohort study was conducted to examine the effect of anti-EPO on the risk of developing anemia over time.. The study population consisted of 113 HIV-1 seropositive patients, who were screened for the presence of anti-EPO, with a mean+/-SD follow up of 105+/-40 months, for a total of 2190 visits. Anti-EPO were detected with an ELISA assay.. Anti-EPO were detected in 41% (46/113) at enrollment and 29% (320/1094) for all visits, and were associated with higher EPO levels for all visits (45.7+/-60.4 vs. 31.8+/-31.7 IU/ml, p<0.001). After adjusting for other significant confounders, anti-EPO has been associated with increased risk of anemia both at enrollment (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.25-20.49) as well as for all visits ([OR], 2.15; 95% [CI]: 1.29-3.56). During follow up, a decline in prevalence of both anti-EPO and anemia was observed as the percentage of patients receiving HAART was increasing.. Anti-EPO are an independent risk factor for anemia in HIV-1-infected patients. HAART seems to reduce both anti-EPO and anemia prevalence.

Topics: Adult; Anemia; Autoantibodies; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Prognosis

We examined the prospective associations between breast milk concentrations of erythropoietin, a factor with trophic effects on infant gut epithelia, and the risk of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) through breast-feeding in a study of 59 MTCT cases and 116 controls nested within a cohort of antiretroviral-naive HIV-infected Tanzanian women. Controls were matched to cases on the basis of the time from birth when the breast milk sample was collected. The risk of MTCT was inversely related to breast milk erythropoietin concentration (adjusted odds ratio for highest vs lowest erythropoietin concentration tertile, 0.34 [95% confidence interval, 0.14-0.82]; P = .02). These results suggest a protective effect of breast milk erythropoietin against MTCT.

Topics: Adult; Case-Control Studies; Erythropoietin; Female; HIV Infections; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Milk, Human; Pregnancy; Prospective Studies; Risk Assessment; Tanzania

Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) protects against HIV/gp120-mediated neuronal damage in culture and in vivo.. Initially, we tested the neuroprotective effects of various concentrations of EPO, IGF-I, or EPO+IGF-I from gp120-induced damage in vitro. To assess the chronic effects of EPO+IGF-I administration in vivo, we treated HIV/gp120-transgenic or wild-type mice transnasally once a week for 4 months and subsequently conducted immunohistochemical analyses.. Low concentrations of EPO+IGF-I provided neuroprotection from gp120 in vitro in a synergistic fashion. In vivo, EPO+IGF-I treatment prevented gp120-mediated neuronal loss, but did not alter microgliosis or astrocytosis. Strikingly, in the brains of both humans with HAND and gp120-transgenic mice, we found evidence for hyperphosphorylated tau protein (paired helical filament-I tau), which has been associated with neuronal damage and loss. In the mouse brain following transnasal treatment with EPO+IGF-I, in addition to neuroprotection we observed increased phosphorylation/activation of Akt (protein kinase B) and increased phosphorylation/inhibition of glycogen synthase kinase (GSK)-3beta, dramatically decreasing downstream hyperphosphorylation of tau. These results indicate that the peptides affected their cognate signaling pathways within the brain parenchyma.. Our findings suggest that chronic combination therapy with EPO+IGF-I provides neuroprotection in a mouse model of HAND, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling. This combination peptide therapy should therefore be tested in humans with HAND.

Topics: Administration, Intranasal; Adult; Animals; Apoptosis; Cells, Cultured; Cerebral Cortex; Chromones; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Embryo, Mammalian; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; HIV Envelope Protein gp120; HIV Infections; Humans; Immunoprecipitation; Insulin-Like Growth Factor I; Male; Mice; Mice, Transgenic; Middle Aged; Morpholines; Nerve Tissue Proteins; Neuroglia; Neurons; Neuroprotective Agents; Olfactory Bulb; Phosphorylation; Rats; tau Proteins

Anemia is a significant problem in elderly patients. Although many anemic elderly patients can be diagnosed with nutritional deficiency, anemia of chronic inflammation or comorbid diseases that explain their decreased hematocrit, the etiology of anemia in a significant fraction remains obscure. There is evidence to suggest that the hematopoietic stem cell displays increasing erythropoietin (EPO) resistance with age. EPO levels rise in elderly, nonanemic patients, and it is hypothesized that there is an interplay between this rising demand for EPO and the decreasing ability of the aging kidney to produce adequate hormone to meet that need. There is further considerable evidence that aging is associated with increased proinflammatory cytokine expression and that many of these cytokines can contribute to EPO insensitivity. Consequently, genetic variation in the expression of these proinflammatory cytokines may influence the development of anemia in elderly patients, both through induction of hepcidin expression (anemia of inflammation) and through cytokine suppression of erythroid colony formation. The impact of inflammatory mediators, EPO insensitivity, and other factors that may act on the hematopoietic stem cell to decrease erythropoiesis are under active study and should serve to elucidate the pathophysiology of this important cause of morbidity and mortality in elderly individuals. A better understanding of the pathophysiology of anemia in elderly patients should provide critical entry points for interventions that will improve survival and quality of life in the aging population.

Topics: Aged; Aging; Anemia; Biomarkers; Erythropoietin; History, 21st Century; HIV Infections; Humans; Inflammation

The primary cause of anemia in HIV-infected patients with ESRD is diminished production of erythropoietin. Although most patients respond to recombinant erythropoietin, the response may be blunted in patients with ESRD and concomitant viral or bacterial infections. Previous studies demonstrated a response to erythropoietin by HIV-infected ESRD patients, but hematocrit levels on average were only 27-29%. We were interested in determining if KDOQI guidelines could be met in these patients. Hematocrits and epogen doses of all HIV-positive patients who were undergoing hemodialysis at the Nassau University Medical Center Dialysis Unit between September 2002 and March 2003 were compared to matched controls in our hemodialysis unit. The hematocrit levels in our population were higher than those reported in earlier papers. In our patient population, the mean hematocrit was 37.5, whereas the mean hematocrit levels in the HIV group in previous papers were 27-29%. HIV-infected patients did require higher erythropoietin dosages than controls, but similar doses were used as compared to previous studies. HIV patients on hemodialysis can achieve KDOQI target hematocrits. The difference in route of iron administration and iron stores may explain the higher hematocrit levels in our HIV patient population as compared to previous trials.

Topics: Anemia, Hypochromic; Black or African American; Drug Administration Schedule; Erythropoietin; Hematocrit; Hemoglobins; HIV Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; New York; Practice Guidelines as Topic; Renal Dialysis

Impaired erythropoiesis is a key abnormality described in untreated HIV-1 disease. Most of the available data on HIV-associated hematopoietic abnormalities were obtained using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter (and intra)-individual variability in the number of cultured precursors. Aim of this study was to assess the erythropoietic capability of purified CD34+ progenitors through a longitudinal analysis of burst-forming units-erythroid (BFU-E) growth before and after antiretroviral therapy (ART).. Twelve HIV-infected individuals were studied before and after ART; 31 HIV-uninfected individuals were enrolled as controls. CD34+ progenitors were purified from peripheral blood by immunomagnetic sorting and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor, interleukin-3, and erythropoietin. Serum levels of iron, transferrin, transferrin saturation index, soluble transferrin receptor, ferritin, and erythropoietin were also evaluated.. Baseline BFU-E levels were increased in untreated HIV-infected individuals when compared with controls but declined significantly after successful ART. In contrast, serum levels of erythropoietin and soluble transferrin receptor increased significantly after ART.. These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective erythropoiesis and accumulation of erythroid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of BFU-E levels.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cell Differentiation; Cells, Cultured; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Diseases; HIV Infections; HIV-1; Humans; Interleukin-3; Longitudinal Studies; Male; Middle Aged; Stem Cell Factor

The natural history of anemia related to interferon/ribavirin (IFN/RBV) treatment in patients with human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfection is not completely understood. The current 8-week, multicenter, observational study characterized anemia over the course of HCV treatment in patients with HIV/HCV coinfection. Eligible HIV/HCV coinfected patients were receiving care in community-based and academic institutions and were on stable antiretroviral therapy and initiating IFN/RBV therapy. Hb, sEPO, reticulocytes, transfusions, laboratory values (e.g., total bilirubin), and IFN and RBV dosages were monitored weekly. Ninety-one patients were analyzed (mean age, 46 years; 71% on HAART) and 53 patients completed the study. Mean Hb decreased significantly (5.0 g/dl) within 1 week of initiating IFN/RBV therapy (p = 0.0002); Hb nadir occurred at a median of 37 days. Maximum Hb decreases of > or =2.0 g/dl occurred in 56 (62%) patients and > or =3.0 g/dl occurred in 45 (49%) patients. Reticulocyte count increased within the first 2 weeks and sEPO peaked at week 3. Mean increase from baseline to week 2 in reticulocyte count and sEPO, respectively, was 1.3% (n = 74) and 45.0 mIU/ml (n = 80) (p < 0.0001 for each parameter), and from baseline to week 8 was 0.9% (n = 48) and 41.0 mIU/ml (n = 52) (p < or = 0.0001 for each parameter). Adverse events (AEs) were the most common reason for study discontinuation (66% of discontinuing patients). Among the 25 patients who discontinued due to AEs, 84% discontinued due to anemia (n = 21). Significant decreases in Hb were observed in HIV/HCV-coinfected patients within 1 week of initiating IFN/RBV therapy. sEPO and reticulocyte increases were blunted in response to anemia; Hb levels did not return to baseline values and anemia was a frequent reason for discontinuing the study.

Topics: Adolescent; Adult; Aged; Anemia; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; Black People; Cell Count; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Hepatitis C, Chronic; Hispanic or Latino; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Protease Inhibitors; Recombinant Proteins; Reticulocytes; Retrospective Studies; Reverse Transcriptase Inhibitors; Ribavirin; Time Factors; Treatment Outcome; White People; Zidovudine

Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis.. An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point.. Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa.. Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.

Topics: Adult; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; HIV Infections; Humans; Injections, Intravenous; Kidney Diseases; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Conflict of Interest; Drug Industry; Epoetin Alfa; Erythropoietin; Hemoglobins; HIV Infections; Humans; Recombinant Proteins

Topics: Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; HIV Infections; Humans; Recombinant Proteins

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Topics: Anemia; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; Epoetin Alfa; Erythropoietin; Forecasting; Hepatitis C; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Anemia is a common comorbidity with HIV. Before the highly active antiretroviral therapy (HAART) era, anemia was found to be associated with decreased survival. This study examined the prevalence of anemia since HAART's availability and the associations between anemia treatments and survival.. Anemia prevalence in a cohort of HIV-infected persons was described. In a smaller cohort of HIV-infected anemic patients, survival was modeled with a time-dependent proportional hazards regression model adjusting for CD4+ T-lymphocyte count, plasma HIV RNA concentration load, hemoglobin (Hb) level, and other factors.. Anemia (Hb level < 10.5 g/dL, or physician diagnosis) decreased from 13 to 5 percent (p < 0.05) in 1996 through 2001. Anemia prevalence was highest (24-35%) and did not decrease among patients with CD4 count less than 100 cells per mL. In total, 216 severely anemic HIV-infected individuals (mean Hb level, 8.1 g/dL) followed for a median of 13 months had a 37-percent mortality rate. Of these, 22 percent were untreated (13% mortality rate), 42 percent received transfusion alone (52% mortality), 12 percent received epoetin alfa alone (19% mortality), and 24 percent received both (47% mortality). Transfusion was associated with a threefold excess mortality risk, but epoetin alfa prescription was not associated with mortality.. The prevalence of anemia decreased in the HAART era, and transfusion was positively associated with risk of death, suggesting limiting use of transfusions in nonemergency situations.

Topics: Adolescent; Adult; Anemia; Antiretroviral Therapy, Highly Active; Blood Transfusion; CD4 Lymphocyte Count; Cohort Studies; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Prevalence; Proportional Hazards Models; Recombinant Proteins; Survival Analysis; Treatment Outcome; Viral Load; Washington

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. Presently, there are no effective therapies for this painful neuropathy. The pathology of HIV-SN is characterized by 'dying back' sensory axonal degeneration and a more modest loss of dorsal root ganglion (DRG) sensory neurons. It has been hypothesized that HIV-SN results from neurotoxicity by secreted viral proteins, such as the HIV envelope glycoprotein gp120. Furthermore, neurotoxicity by dideoxynucleoside (DDX) agents, results in the observed higher incidence of HIV-SN in HIV-infected patients taking these antiretroviral drugs. In this study we show that administration of picomolar amounts of the hormone erythropoietin (EPO) prevents sensory axonal degeneration and in vitro DRG neuronal death by both gp120 and ddC (a neurotoxic DDX drug). Our results suggest that EPO may be useful in the treatment of HIV-SN.

Topics: Animals; Cells, Cultured; Dose-Response Relationship, Drug; Erythropoietin; Ganglia, Spinal; HIV Infections; HIV-1; Neuroprotective Agents; Polyneuropathies; Rats; Rats, Sprague-Dawley

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Anemia commonly occurs in patients with cancer or human immunodeficiency virus (HIV) infection as a result of the disease, its treatment, or both. The negative impact of anemia on patient quality of life (QOL), functional status, and treatment outcomes underscores the need for its correction in these patients. In anemic patients with cancer or HIV infection, treatment with epoetin alfa increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves QOL. In both settings, the gains in overall QOL have been significantly and directly related to increases in Hb, with maximum QOL gains in the range of Hb levels of 11-13 g/dL, supporting the need to achieve and maintain Hb levels > or =12 g/dL in an effort to preserve and maximize QOL benefits. A potential survival benefit has also been associated with correction of anemia in patients with HIV infection--and possibly in those with cancer as well.

Topics: Anemia; Clinical Trials as Topic; Disease Progression; Epoetin Alfa; Erythropoietin; HIV; HIV Infections; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Hepatitis C virus (HCV) infection is a significant worldwide health care problem. Nearly one-third of all patients infected with human immunodeficiency virus (HIV) are coinfected with HCV. Compared with HIV-monoinfected persons, coinfected individuals experience more rapid progression of fibrosis and higher incidence of cirrhosis and death as a result of liver disease. Treatment for HCV infection includes ribavirin (RBV) plus interferon alfa (IFN-alpha) or pegylated IFN, a combination treatment associated with anemia that may require RBV dose reduction or discontinuation. IFN-RBV-associated anemia is more profound among coinfected patients, who have a high prevalence of pretreatment anemia and may also be taking other medications causing anemia. Epoetin alfa administration to HCV-infected patients with IFN-RBV-related anemia can significantly increase hemoglobin levels and maintain significantly higher RBV doses compared with patients treated with RBV dose reduction alone. Higher RBV doses and adherence to HCV therapy have been associated with higher sustained virologic response (SVR) rates. Maintenance of RBV dose with epoetin alfa may improve adherence, thereby affecting SVR.

Topics: Anemia; Antiviral Agents; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

Topics: Adenine; Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Resistance, Microbial; Drug Therapy; Epoetin Alfa; Erythropoietin; Hepatitis C; HIV Infections; Humans; Lamivudine; Organophosphonates; Organophosphorus Compounds; Recombinant Proteins; Saquinavir; Tenofovir; Zidovudine

A third to a half the 1.5 million HIV-positive children in the world today acquired their infection via breastfeeding. However, what protects the 85% of breastfed babies of HIV-infected mothers who do not become infected? We postulate that erythropoietin (EPO), a hormone in human milk, has a role in the prevention of HIV transmission during breastfeeding. EPO might maintain mammary epithelium integrity, thereby reducing viral loads in milk, or maintain intestinal epithelial integrity in the breastfed neonate, and thus preventing ingested milk-borne virus being infective. This hypothesis could be tested by administration of recombinant human EPO parenterally to HIV-infected mothers or enterally to breastfed babies, or both, and assessment of the effect on mammary permeability, viral load in milk, and intestinal permeability in babies. If our hypothesis is correct, EPO treatment for mother or baby, or both might help prevent transmission of HIV.

Topics: Breast Feeding; Erythropoietin; Female; Global Health; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Milk, Human

Topics: Anemia; Drug Labeling; Epoetin Alfa; Erythropoietin; Fraud; HIV Infections; Humans; Recombinant Proteins; United States; United States Food and Drug Administration

Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-alpha (TNF-alpha), neopterin, CD4(+) lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 microg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log(10) plasma erythropoietin = 2.86 - 0.016.hemoglobin, and log(10) plasma erythropoietin = 4.11 - 0.028.hemoglobin, respectively, with a difference in the slope of the regression lines between log(10) erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.

Topics: Anemia, Iron-Deficiency; CD4 Lymphocyte Count; Erythropoietin; Female; Ferritins; Hemoglobins; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Infant; Iron; Male; Nutritional Status; Tumor Necrosis Factor-alpha; Uganda

Topics: Blood Donors; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Fees, Pharmaceutical; Hematinics; HIV Infections; Hypertension, Renal; Neoplasms; Premedication; Preoperative Care; Recombinant Proteins; Renal Insufficiency

Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting.. For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied.. Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869.. Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Brachytherapy; Cisplatin; Costs and Cost Analysis; Erythrocyte Transfusion; Erythropoietin; Female; Hepatitis B; Hepatitis C; HIV Infections; Humans; Middle Aged; Probability; Radiation-Sensitizing Agents; Retrospective Studies; Uterine Cervical Neoplasms

Topics: Anemia; Erythropoietin; Female; HIV Infections; Humans; Infant; Malawi; Male; Regression Analysis

Topics: Adult; Anemia, Hypochromic; Biomarkers; Erythropoietin; Female; Ferritins; HIV Infections; Humans; Iron; Iron Deficiencies; Male; Predictive Value of Tests; Protoporphyrins; Receptors, Transferrin; Recombinant Proteins; Sensitivity and Specificity; Transferrin

In a cohort of 204 unselected consecutive human immunodeficiency virus type 1 (HIV-1)-infected patients, the association of circulating autoantibodies to endogenous erythropoietin (EPO) with HIV-1-related anemia was studied. Circulating autoantibodies to EPO were present in 48 (23.5%) of the 204 patients studied. Circulating autoantibodies were an independent predictor of anemia (odds ratio [OR]=5.0; 95% confidence interval [CI], 2.5-9.9), as strong as other known causes of anemia. The association of anti-EPO antibodies with anemia became stronger when the analysis was limited to the group of patients without any medical condition causing anemia (OR=10.4; 95% CI, 3.2-33.9). Moreover, the effect on hemoglobin levels remained significant even after adjusting for other anemia parameters. Anti-EPO autoantibodies were associated with higher EPO levels (r=.25, P=.012) and with a more prominent EPO response to anemia. Our findings suggest that autoimmunity, among other factors, may contribute to the pathogenesis of HIV-1-related anemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Autoantibodies; Cohort Studies; Erythropoietin; Female; Hemoglobins; HIV Infections; HIV-1; Humans; Male; Middle Aged

Several clinical studies have suggested that anemia is an independent risk factor for dying in patients with HIV disease. We analyzed data from a large urban HIV clinical practice in Baltimore to assess the annual incidence of anemia, the risk of dying in patients who develop anemia, and the association between recombinant human erythropoietin use to treat anemia and subsequent survival. In 2348 patients observed between 1989 and 1996, 498 (21%) developed at least grade 1 anemia (hemoglobin <9.4 g/dl); 95 (4%) developed grade 4 anemia (hemoglobin <6.9 g/dl). Development of anemia was associated with decreased survival, independent of other prognostic factors. Use of erythropoietin was more likely in patients of nonminority race, those who did not inject drugs, those with a lower CD4 count or AIDS, and those being treated for cytomegalovirus disease (p < .05). Adjusting for these factors as well as severity of anemia, age, diagnosis of opportunistic disease, blood transfusion, and antiretroviral therapy in a time-dependent Cox proportional hazards analysis, erythropoietin use (n=91) was associated with a decreased hazard of dying (relative hazard [RH]=0.57; 95% confidence interval [CII, 0.40-0.81; p=.002). Although we cannot rule out a treatment selection bias, adjusting for available prognostic factors and factors potentially associated with a decision to use erythropoietin suggests that erythropoietin for treatment of anemia is associated with improved survival in HIV disease.

Topics: Adult; Anemia; Anti-HIV Agents; Anti-Infective Agents; Blood Transfusion; Erythropoietin; Female; Ganciclovir; Hemoglobins; HIV Infections; Humans; Incidence; Longitudinal Studies; Male; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged < 13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels.. A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres.. Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radioimmunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network.. The study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/l, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.01 for ZDV-treated and ZDV-naive subjects).. SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.

Topics: Anemia; Anti-HIV Agents; Bahamas; Canada; Child; Child, Preschool; Cross-Sectional Studies; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Infant; Male; Renal Insufficiency; Zidovudine

HIV infection is associated with a number of blood abnormalities. Anemia is a frequent consequence, affecting 15 percent of asymptomatic HIV-positive individuals and 85 percent of those with AIDS. Anemia is defined by a decreased number of red blood cells. Individuals with anemia have a diminished capacity to carry oxygen in their blood and suffer from fatigue, difficulty breathing, increased heart rate, pallor, and occasionally heart murmurs. Treatment depends on the underlying cause of anemia.

Topics: Anemia; Anti-HIV Agents; Bone Marrow; Erythropoiesis; Erythropoietin; HIV Infections; Humans; Kidney; Recombinant Proteins; Zidovudine

Lisa Capaldini, a physician who treats patients with HIV-related fatigue, discusses symptoms, diagnosis techniques, and treatments of depression, anemia, and various other roots of fatigue in HIV-positive patients. Biochemical depression, caused by abnormal levels of serotonin and norepinephrine in the brain, is easily misdiagnosed or overlooked. Physical and emotional symptoms of depression mirror common effects of HIV such as exhaustion, anger, and irritability. Knowing the history of depression prior to HIV infection, including previous drug abuse and family history of depression, will help to diagnose fatigue. Dr. Capaldini recommends antidepressants provided the condition is properly diagnosed and the side effects are not harmful to the patient. Selective serotonin reuptake inhibitors (SSRI), the most frequently prescribed antidepressants, can cause short term sexual dysfunction. Bupropion and Wellbutrin can be prescribed to avoid this side effect. Psychotherapy can be effective if therapists are familiar with HIV disease and can distinguish between symptoms brought on by behavior, addictive habits, or pre-existing depression. Consideration also must be given to drug interactions, particularly with the antiretrovirals ritonavir and delavirdine, which can cause seizures or disturb cardiac rhythm. Anemia is most noticeable after physical exertion, and symptoms are more evident based on the increased rate that red blood cells move out of the normal range. To determine the course of treatment, physicians need to clarify the cause of anemia. Anemia can be caused by drugs, vitamin deficiencies, or other nutritional problems. Adrenal insufficiency, methemoglobinemia, and malnutrition are also causes of fatigue. Diagnosing fatigue due to hepatitis B or C, rather than HIV, can be achieved by measuring hepatitis levels and observing T cell counts and viral load. Dr. Capaldini suggests that proper diet and exercise prevent fatigue from getting worse.

Topics: Adrenal Insufficiency; Anemia; Anti-HIV Agents; Antidepressive Agents; Depression; Drug Interactions; Erythropoietin; Fatigue; Female; Hepatitis, Viral, Human; HIV Infections; Humans; Male; Methemoglobinemia; Nutrition Disorders

Epoietin alfa (EPO) is a synthetic version of erythropoietin. Initially approved by the Food and Drug Administration (FDA) for treating anemia in patients on kidney dialysis, the approval was later expanded to include people with AZT-related anemia, those undergoing chemotherapy, and those undergoing surgery that requires blood transfusions. In clinical studies, EPO raised hematocrit, which indicates increased red blood cells, and therefore decreased the number of blood transfusions needed. For patients with high blood pressure, or for patients who have anemia from iron or folate insufficiency, EPO should not be used.

Topics: Anemia; Anti-HIV Agents; Clinical Trials as Topic; Erythropoietin; Female; HIV Infections; Humans; Male; Pregnancy; Recombinant Proteins; Zidovudine

People with advanced HIV infection and anemia are at greater risk of complications from red blood cell transfusions than those who are not HIV-positive. The advent of synthetic hematopoietic growth factors has provided an alternative for managing anemia. Epoetin alfa is a recombinant human erythropoietin (rHuEpo), which is an example of a hematopoietic growth factor, and it was approved for treatment of anemia in HIV-positive patients in 1991. The origin and makeup of rHuEpo are examined, as are the effects of regulating its levels with different drug treatments. Because the effects of blood transfusions to raise hematocrit levels are short-lived, fewer transfusions are being performed in favor of using rHuEpo. Also, side effects of anemia, as well as statistics of survival are somewhat improved by this treatment. Several possible causes for anemia in HIV-infected patients are cited, including atypical mycobacteria, toxoplasma gondii, and side effects resulting from drug therapy. Additional studies are examined.

Topics: Anemia; Erythropoietin; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P < 0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = -0.29; P < 0.01). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II (P < 0.01). The results of this study suggest that similar to its action in vitro, activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly reflected by elevations of soluble TNF receptor levels.

Topics: Adult; Aged; Anemia; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Interleukin-6; Male; Middle Aged; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha

To determine the factors that govern their response to erythropoietin (EPO), we conducted a cross-sectional study of all patients in four outpatient hemodialysis facilities in Brooklyn, NY, who had end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection and were receiving recombinant EPO. We also compared the hematocrit and EPO requirements of these patients to those of a control group of hemodialysis patients without HIV infection. We documented known duration of HIV infection, and total CD4 count was measured once. In both groups, hematocrit was measured weekly for 5 weeks and a mean value calculated for each subject. Transferrin saturation was measured twice and a mean value calculated for each subject. Intensity of hemodialysis was assessed by measuring both percent reduction of urea and serum albumin concentration twice; mean values were calculated for each subject. Twenty-nine (88%) of 33 study subjects had acquired immunodeficiency syndrome. Mean known duration of HIV infection was 49 +/- 32.5 months (median, 48 months), and mean total CD4 count was 143 +/- 152.4 cells/mm3 (median, 72 cells/mm3). Mean hematocrit in the study subjects was 27.4% +/- 4.7% compared with 27.6% +/- 3.7% in the controls (P = 0.69). Mean thrice-weekly EPO dose was higher in the study subjects (90 +/- 52 U/kg body weight) than in the controls (62 +/- 36 U/Kg body weight) (P = 0.001). Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55). There was an inverse correlation between hematocrit and dose of EPO (r = -0.5; P = 0.003). Multiple regression analysis showed that transferrin saturation (P = 0.01) and percent reduction of urea (P = 0.003) had direct correlations with hematocrit after adjustment for other factors. There was an inverse relationship between hematocrit and dose of EPO (P = 0.0006). We conclude that in patients with ESRD and HIV infection receiving hemodialysis, the response to EPO (hematocrit) is modulated by the dose of EPO, quantity of hemodialysis, and transferrin saturation, but not by the severity of HIV disease. Hemodialysis patients infected with HIV receive a higher dose of EPO than those without HIV infection.

Topics: Adult; CD4 Lymphocyte Count; Cross-Sectional Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; HIV Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Renal Dialysis; Serum Albumin; Severity of Illness Index; Transferrin; Treatment Outcome

The objectives of this study were to compare the costs and benefits of recombinant human erythropoietin (r-HuEPO) relative to repeated transfusions in the treatment of zidovudine (AZT)-related anemia among HIV-infected children. The study was based on a tertiary care Canadian Pediatric Hospital Model. A decision analytic structure was used for the evaluation of cost-effectiveness. The decision tree involved two options. In option A:r-HuEPO, subjects receive r-HuEPO three times weekly at home for 1 year, whereas in B:no r-HuEPO, transfusions are given on a monthly basis in a medical short-stay unit over a 1-year period. Probabilities of various outcomes and downstream events were obtained from a literature review. The analysis was conducted from the perspective of the health-care system and utilized standard cost-effectiveness methodology. The results indicated that for every child receiving r-HuEPO, the total cost is Can $11,245 for 1 year compared with $3,130 per year for those in B:no r-HuEPO. The incremental cost effectiveness of A:r-HuEPO relative to B:no r-HuEPO is $1,373 per transfusion episode averted. The order of magnitude of the results was not significantly affected by changes in any of the assumptions used for the cost estimates or baseline probability values.

Topics: Anemia; Anti-HIV Agents; Blood Transfusion; Child; Cost-Benefit Analysis; Decision Trees; Erythropoietin; Health Care Costs; HIV Infections; Humans; Outcome Assessment, Health Care; Sensitivity and Specificity; Zidovudine

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

Topics: Anemia; Biomarkers; Biopterins; Erythropoietin; Ferritins; Hemoglobins; HIV Infections; Humans; Interferon-gamma; Leukemia; Neoplasms; Neopterin; Reference Values

The authors gave recombinant human erythropoietin to four anaemic patients with HIV-infection treated with zidovudine. After erythropoietin administration an increase in haemoglobin, erythrocytes and haematocrit was observed and patients could continue AZT therapy.

Topics: Adult; Anemia; Erythropoietin; HIV Infections; Humans; Recombinant Proteins; Zidovudine

Topics: Anemia; Erythropoietin; HIV Infections; HIV-1; Humans; Kidney Failure, Chronic

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: Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; HIV Infections; Humans

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: Adult; Ambulatory Care; Catheters, Indwelling; Combined Modality Therapy; Erythropoietin; Female; HIV Infections; Humans; Male; Opportunistic Infections; Physician's Role; Terminal Care; Zidovudine

Topics: Anemia; Erythropoietin; HIV Infections; HIV-1; Humans; United States; United States Food and Drug Administration; Zidovudine