epoetin-alfa and HIV-Infections

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

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

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

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

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

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

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

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

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

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

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