THE SAFETY AND EFFICACY OF ZIDOVUDINE (AZT) IN THE TREATMENT OF SUBJECTS WITH MILDLY SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV) INFECTION - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
THE SAFETY AND EFFICACY OF ZIDOVUDINE (AZT) IN THE TREATMENT OF SUBJECTS WITH MILDLY SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV) INFECTION - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
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DOI：
10.7326/0003-4819-112-10-727
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发表时间：
1990-05-15
影响因子：
39.2
通讯作者：
ANDERSON, J
中科院分区：
文献类型：
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作者：
FISCHL, MA;RICHMAN, DD;ANDERSON, J
本研究的目的是评估齐多夫定早期治疗人类免疫缺陷病毒 1 型 (HIV) 感染的有效性和安全性。该设计是一项双盲、随机、安慰剂对照试验，通过治疗前 CD4 T 淋巴细胞计数对受试者进行分层。这是艾滋病临床试验单位的一项多中心试验，纳入了 711 名患有轻度艾滋病毒感染症状的受试者。 351 名受试者被分配到安慰剂组，360 名受试者被分配到齐多夫定，每 4 小时口服 200 毫克。中位随访时间为 11 个月。测量和主要结果是，51 名受试者出现了获得性免疫缺陷综合症 (AIDS)、晚期艾滋病相关综合症或死亡作为第一个严重事件。对于治疗前 CD4 T 淋巴细胞超过 200 个但低于 500 个/mm3 的受试者分层，安慰剂接受者发生 34 起事件，齐多夫定接受者发生 12 起事件（P = 0.0002；相对风险 [RR] 估计，3.23 [95% CI，1.67 至 6.24]）。对于治疗前具有 500 至 799 个 CD4 T 淋巴细胞/mm3 的受试者阶层，安慰剂接受者发生 2 起事件，齐多夫定接受者发生 3 起事件。研究开始时的念珠菌病独立增加发生事件的风险（P = 0.005；RR 估计，2.3 [95% CI，1.29 至 4.12]）；研究开始时的 HIV 抗原血症也增加了这种风险（P = 0.01；RR 估计，2.1 [95% CI，1.2 至 3.8]）。治疗 4 周后，治疗组之间 CD4 T 淋巴细胞计数超过 200 个但低于 500 个 CD4 T 淋巴细胞/mm3 的受试者存在显着差异（P = 0.002）。差异持续到第 52 周。CD4 T 淋巴细胞/mm3 为 500 或更多的受试者中发生的变化不太显着。齐多夫定接受者的 HIV 抗原血清水平显着下降。齐多夫定接受者中分别有 5% 和 4% 发生严重贫血和中性粒细胞减少症，安慰剂接受者中分别有 0% 和 1% 发生严重贫血和中性粒细胞减少症。总之，齐多夫定可延缓 HIV 疾病的进展，并且对患有轻度 HIV 疾病且 CD4 T 淋巴细胞低于 500 个/mm3 的受试者产生很小的毒性。
The objective of this study was to evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. The design was a double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. This was a multicenter trial at AIDS Clinical Trials units, and seven hundred eleven subjects with mildly symptomatic HIV infection were included. Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. The measurements and main results were fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the teratment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. In conclusion zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.