Volberding P A, Lagakos S W, Grimes J M, Stein D S, Rooney J, Meng T C, Fischl M A, Collier A C, Phair J P, Hirsch M S
University of California, San Francisco, USA.
N Engl J Med. 1995 Aug 17;333(7):401-7. doi: 10.1056/NEJM199508173330701.
The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine therapy given immediately with deferred therapy in such subjects.
Beginning in 1987, subjects with asymptomatic HIV infection and 500 or more CD4 cells per cubic millimeter were randomly assigned to receive placebo or zidovudine (either 500 or 1500 mg per day, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, survival free of the acquired immunodeficiency syndrome (AIDS), toxic effects, and changes in CD4 cell counts.
There were 1637 subjects who could be evaluated: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed for up to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to AIDS or death vs. 81 and 74, respectively; P = 0.95 and P = 0.13) or in overall survival (51 deaths vs. 47 and 46; P = 0.25 and P = 0.16). The decline in CD4 cells was slower in both immediate-therapy groups than in the deferred-therapy group (P < 0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P < 0.001).
In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.
对于无症状的人类免疫缺陷病毒（HIV）感染者，当CD4细胞计数超过每立方毫米500个时，齐多夫定的临床益处尚未得到证实。我们比较了在此类受试者中立即给予齐多夫定治疗与延迟治疗的效果。
从1987年开始，将无症状HIV感染且CD4细胞计数每立方毫米500个或更多的受试者随机分配接受安慰剂或齐多夫定（每天500毫克或1500毫克，立即开始）。1989年，研究进行了修改，当CD4细胞计数降至每立方毫米500个以下时，提供每天500毫克齐多夫定的开放标签治疗（延迟治疗）。研究终点包括总生存期、无获得性免疫缺陷综合征（AIDS）生存期、毒性作用以及CD4细胞计数的变化。
共有1637名受试者可进行评估：延迟治疗组547名，立即接受500毫克齐多夫定治疗组549名，1500毫克组541名。受试者随访长达6.5年（各组中位数分别为4.8年、4.8年和4.9年）。延迟治疗组与低剂量组或高剂量组相比，无AIDS生存期无显著差异（进展为AIDS或死亡的病例分别为81例、81例和74例；P = 0.95和P = 0.13），总生存期也无显著差异（死亡病例分别为51例、47例和46例；P = 0.25和P = 0.16）。两个立即治疗组的CD4细胞下降速度均比延迟治疗组慢（两者P均<0.001）。不良反应不常见，在研究修改之前，各治疗组的发生率相似，但1500毫克组严重贫血和粒细胞减少症的发生率高于延迟治疗组（P < 0.001）。
对于每立方毫米CD4细胞计数500个或更多的无症状HIV感染成年人，齐多夫定治疗可减缓CD4细胞计数下降，但不能显著延长无AIDS生存期或总生存期。这些结果不支持在此人群中常规使用齐多夫定单药治疗。
