Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials
Henry, D.H.; Beall, G.N.; Benson, C.A.; Carey, J.; Cone, L.A.; Eron, L.J.; Fiala, M.; Fischl, M.A.; Gabin, S.J.; Gottlieb, M.S.
Annals of Internal Medicine 117(9): 739-748
1992
ISSN/ISBN: 0003-4819 PMID: 1416576 Document Number: 392609
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 lt 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 ( ltoreq 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 lt 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 of 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 ( ltoreq 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.