RECOMBINANT-HUMAN-ERYTHROPOIETIN IN THE TREATMENT OF ANEMIA ASSOCIATED WITH HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION AND ZIDOVUDINE THERAPY - OVERVIEW OF 4 CLINICAL-TRIALS

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