Phair J P, Abels R I, McNeill M V, Sullivan D J
Comprehensive AIDS Center, Northwestern University Medical School, Chicago, IL.
Arch Intern Med. 1993 Dec 13;153(23):2669-75.
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.
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.
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.
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.
与人类免疫缺陷病毒感染相关的贫血可能是由于疾病本身或同时使用的药物（如齐多夫定）导致红细胞生成减少。临床研究表明，重组人促红细胞生成素（r-HuEPO）可有效纠正基线血清促红细胞生成素水平为500 U/L或更低的接受齐多夫定治疗的人类免疫缺陷病毒感染患者的贫血。一项治疗性研究新药方案对1943例获得性免疫缺陷综合征贫血患者给予了r-HuEPO，并进行了研究。
入选标准包括获得性免疫缺陷综合征的临床诊断、血清促红细胞生成素水平为500 U/L或更低、血细胞比容小于0.300以及年龄在12岁或以上。初始r-HuEPO剂量为皮下注射4000 U，每周6天。根据反应情况，r-HuEPO剂量可依次增加至皮下注射8000 U，每周6天。这是一项开放标签的多中心治疗方案。共有1943例患者由510名研究人员进行治疗。疗效评估基于r-HuEPO相对于基线对血细胞比容水平和输血需求的影响。收集研究人员认为可能与r-HuEPO治疗相关的不良事件以评估安全性。
r-HuEPO治疗使平均血细胞比容从基线的0.280在第12周时升至0.331，在第24周时升至0.338。在整个研究过程中直至第54周，这种升高一直持续。总体而言，40%的患者（769/1943）在研究入组前紧挨着的6周间隔期（基线）至少需要一次输血。在r-HuEPO治疗12周和24周后，相应的百分比分别为22%（311/1387）和18%（119/650）。44%的患者出现了对治疗的反应，定义为血细胞比容较基线升高0.060，且在达到该血细胞比容之前的28天内未输血。11%的患者报告了与获得性免疫缺陷综合征无明确关联的不良事件。
在1943例接受r-HuEPO治疗的获得性免疫缺陷综合征贫血患者的研究人群中，血细胞比容升高，输血需求减少。r-HuEPO治疗耐受性良好。
