Fischl M A, Stanley K, Collier A C, Arduino J M, Stein D S, Feinberg J E, Allan J D, Goldsmith J C, Powderly W G
University of Miami School of Medicine, Department of Medicine, FL 33101.
Ann Intern Med. 1995 Jan 1;122(1):24-32. doi: 10.7326/0003-4819-122-1-199501010-00004.
To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together.
A randomized, double-blind, controlled trial.
AIDS Clinical Trials units and National Hemophilia Foundation sites.
1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more.
Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d.
The primary end point was time to disease progression or death.
The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3.
We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.
比较继续使用齐多夫定治疗与单独使用扎西他滨或扎西他滨与齐多夫定联合使用的安全性和疗效。
一项随机、双盲、对照试验。
艾滋病临床试验单位和国家血友病基金会站点。
1001例有症状的人类免疫缺陷病毒（HIV）病患者且CD4细胞计数≤300个/mm³，或无症状HIV病患者且CD4细胞计数≤200个/mm³，这些患者已接受齐多夫定治疗6个月或更长时间。
患者被随机分配接受齐多夫定，600mg/天；扎西他滨，2.25mg/天；或齐多夫定，600mg/天加扎西他滨，2.25mg/天。
主要终点是疾病进展或死亡时间。
中位随访时间为17.7个月。齐多夫定组、扎西他滨组和联合治疗组的估计12个月无事件发生率分别为70%、67%和73%（P = 0.26）。趋势分析显示，随着预处理CD4细胞计数增加，联合治疗组的进展率显著低于齐多夫定治疗组（P = 0.027）。对于CD4细胞计数≥150个/mm³的患者，接受联合治疗的患者发生疾病进展或死亡的可能性低于接受齐多夫定治疗的患者（相对危险度，0.51；95%可信区间，0.28至0.93；P = 0.029）。我们观察到扎西他滨组和齐多夫定组之间无差异（相对危险度，0.74；可信区间，0.40至1.36；P = 0.33）。对于CD4细胞计数为50至150个/mm³或＜50个/mm³的患者，我们发现各治疗组之间无差异（分别为P = 0.69和P = 0.57）。严重毒性作用在CD4细胞计数≥150个/mm³的患者中发生频率较低。
我们发现单独使用扎西他滨或与齐多夫定联合使用没有总体益处。然而，趋势分析表明，随着预处理CD4细胞计数增加，联合治疗与齐多夫定相比有更好的结果。
