title: Recombinant human erythropoietin treatment: investigational new drug protocol for the anemia of the acquired immunodeficiency syndrome. Overall results.
abstract: BACKGROUND
  Anemia associated with human immunodeficiency virus infection may be due to reduced erythropoiesis related to the disease itself or to concomitant medications (eg, zidovudine). Clinical studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in correcting the anemia of zidovudine-treated patients infected with human immunodeficiency virus with baseline serum erythropoietin levels of 500 U/L or less. A treatment investigational new drug protocol that provided r-HuEPO to 1943 anemic patients with the acquired immunodeficiency syndrome was studied.
  
  
  METHODS
  Enrollment criteria included a clinical diagnosis of acquired immunodeficiency syndrome, serum erythropoietin level of 500 U/L or less, hematocrit less than 0.300, and age of 12 years or more. The initial r-HuEPO dosage was 4000 U subcutaneously for 6 days each week. On the basis of response, the r-HuEPO dosage could be increased sequentially to 8000 U subcutaneously for 6 days per week. This was an open-label multicenter treatment protocol. A total of 1943 patients were treated by 510 investigators. Efficacy evaluations were based on the effect of r-HuEPO on hematocrit levels and transfusion requirements relative to baseline. Adverse experiences that were considered by the investigator to be possibly related to r-HuEPO therapy were collected to assess safety.
  
  
  RESULTS
  Therapy with r-HuEPO resulted in an increase in mean hematocrit from a baseline of 0.280 to 0.331 at week 12 and 0.338 at week 24. This increase was sustained throughout the course of the study to week 54. Overall, 40% of patients (769/1943) required at least one transfusion in the 6-week interval immediately preceding study entry (baseline). After 12 and 24 weeks of r-HuEPO treatment, corresponding percentages were 22% (311/1387) and 18% (119/650), respectively. Response to therapy, defined as an increase of 0.060 from baseline in hematocrit, with no transfusions within 28 days before achieving that hematocrit, was observed in 44% of patients. Adverse experiences not clearly related to acquired immunodeficiency syndrome were reported by 11% of patients.
  
  
  CONCLUSIONS
  In a study population of 1943 anemic patients with acquired immunodeficiency syndrome treated with r-HuEPO, the hematocrit increased and blood transfusion requirements decreased. Therapy with r-HuEPO was well tolerated.
authors.affiliation: Comprehensive AIDS Center, Northwestern University Medical School, Chicago, IL.
authors.forename: J P
authors.initials: JP
authors.lastname: Phair
authors.forename: R I
authors.initials: RI
authors.lastname: Abels
authors.forename: M V
authors.initials: MV
authors.lastname: McNeill
authors.forename: D J
authors.initials: DJ
authors.lastname: Sullivan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D001803:Blood Transfusion; D003131:Combined Modality Therapy; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects*
chemical_list: D015507:Drugs, Investigational; D011994:Recombinant Proteins; D004921:Erythropoietin; D015215:Zidovudine