Spruance S L, Pavia A T, Mellors J W, Murphy R, Gathe J, Stool E, Jemsek J G, Dellamonica P, Cross A, Dunkle L
Health Sciences AIDS Center, University of Utah School of Medicine, Salt Lake City 84132, USA.
Ann Intern Med. 1997 Mar 1;126(5):355-63. doi: 10.7326/0003-4819-126-5-199703010-00003.
Stavudine is a promising antiretroviral agent, but its clinical efficacy has not been determined.
To evaluate the clinical effect of stavudine (2',3'-didehydro-3'-deoxythymidine) monotherapy in patients with human immunodeficiency virus (HIV) infection.
Randomized, controlled, double-blind trial.
56 outpatient clinics in private practices, universities, and contract research organizations in the United States, France, and Italy.
822 HIV-infected adults who had 50 to 500 CD4+ cells/mm3 and had previously received at least 6 months of zidovudine treatment.
Monotherapy with peroral stavudine capsules or peroral zidovudine capsules.
The primary end point was clinical progression, which was defined as all occurrences of acquired immunodeficiency syndrome (AIDS)-defining events or death.
Patients receiving stavudine reached clinical end points at a rate of 26 per 100 person-years, compared with 32 per 100 person-years for patients receiving zidovudine (relative risk, 0.75 [95% CI, 0.58 to 0.98]; P = 0.03). The risk for death alone was 26% lower in the stavudine group than in the zidovudine group, but the comparison was not statistically significant (relative risk, 0.74 [CI, 0.53 to 1.02]; P = 0.066). The benefit of stavudine therapy was seen in all CD4+ cell strata (< or = 100 cells/mm3, 101 to 300 cells/mm3, and > 300 cells/mm3) and clinical stages of HIV disease (asymptomatic, symptomatic, and AIDS). Four weeks after treatment began, CD4+ cell counts were 30 cells/mm3 higher in the stavudine group than in the zidovudine group; this difference was sustained for 96 weeks (P < 0.001). Nausea and vomiting were more common in patients receiving zidovudine (P < 0.01), and neuropathy occurred more frequently in those receiving stavudine (12% in the stavudine group compared with 4% in the zidovudine group; P < 0.001). Neuropathy resolved completely in many patients (63%) after interruption of stavudine treatment; these patients could resume stavudine therapy at a lower dose.
Stavudine was well tolerated and delayed progression of HIV disease in patients who had previously received 6 or more months of zidovudine treatment. Benefits were apparent in all CD4+ cell strata and clinical stages of HIV disease. Stavudine is an important agent to consider for trials of combination chemotherapy.
司他夫定是一种有前景的抗逆转录病毒药物，但其临床疗效尚未确定。
评估司他夫定（2'，3'-双脱氢-3'-脱氧胸苷）单药治疗人类免疫缺陷病毒（HIV）感染患者的临床效果。
随机、对照、双盲试验。
美国、法国和意大利的56家私人诊所、大学及合同研究机构的门诊。
822例HIV感染的成年人，其CD4 +细胞计数为50至500个/mm³，且此前至少接受过6个月的齐多夫定治疗。
口服司他夫定胶囊或口服齐多夫定胶囊进行单药治疗。
主要终点为临床进展，定义为所有获得性免疫缺陷综合征（AIDS）定义事件或死亡的发生情况。
接受司他夫定治疗的患者达到临床终点的发生率为每100人年26例，而接受齐多夫定治疗的患者为每100人年32例（相对危险度，0.75 [95%可信区间，0.58至0.98]；P = 0.03）。仅死亡风险在司他夫定组比齐多夫定组低26%，但该比较无统计学意义（相对危险度，0.74 [可信区间，0.53至1.02]；P = 0.066）。司他夫定治疗的益处见于所有CD4 +细胞分层（≤100个细胞/mm³、101至300个细胞/mm³和＞300个细胞/mm³）以及HIV疾病的各个临床阶段（无症状、有症状和AIDS）。治疗开始4周后，司他夫定组的CD4 +细胞计数比齐多夫定组高30个细胞/mm³；这种差异持续了96周（P < 0.001）。接受齐多夫定治疗的患者恶心和呕吐更常见（P < 0.01），而接受司他夫定治疗的患者神经病变更频繁（司他夫定组为12%，齐多夫定组为4%；P < 0.001）。许多患者（63%）在中断司他夫定治疗后神经病变完全缓解；这些患者可较低剂量恢复司他夫定治疗。
司他夫定耐受性良好，可延缓此前接受过6个月或更长时间齐多夫定治疗的HIV疾病患者的病情进展。益处见于HIV疾病的所有CD4 +细胞分层和临床阶段。司他夫定是联合化疗试验中值得考虑的重要药物。
