A CONTROLLED TRIAL COMPARING CONTINUED ZIDOVUDINE WITH DIDANOSINE IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
A CONTROLLED TRIAL COMPARING CONTINUED ZIDOVUDINE WITH DIDANOSINE IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
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DOI：
10.1056/nejm199208273270901
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发表时间：
1992-08-27
影响因子：
158.5
通讯作者：
DOLIN, R
中科院分区：
文献类型：
--
作者：
KAHN, JO;LAGAKOS, SW;DOLIN, R
背景：尽管齐多夫定对人类免疫缺陷病毒（HIV）感染患者有效，但其疗效可能会随着长期使用而下降。去羟肌苷是另一种HIV逆转录酶抑制剂。我们评估了将抗HIV治疗从齐多夫定改为去羟肌苷的有效性。
方法：这项多中心、双盲研究涉及913名至少耐受齐多夫定16周的患者。这些患者患有获得性免疫缺陷综合征（AIDS）、每立方毫米CD4细胞数≤300的艾滋病相关综合征，或每立方毫米CD4细胞数≤200的无症状HIV感染。他们被随机分配接受每天600毫克齐多夫定、每天750毫克去羟肌苷或每天500毫克去羟肌苷。
结果：在被分配接受每天500毫克去羟肌苷的298名受试者中，新的艾滋病定义事件和死亡人数明显少于继续接受齐多夫定的受试者（相对风险，1.39；95%置信区间，1.06 - 1.82；P = 0.015）。使用750毫克去羟肌苷时，相较于齐多夫定没有明显益处（相对风险，1.10；95%置信区间，0.86 - 1.42）。去羟肌苷的疗效与先前齐多夫定治疗的持续时间无关。在两个去羟肌苷组中，CD4细胞数量有所改善（P<0.001），但在齐多夫定组中没有改善。去羟肌苷的主要不良反应是周围神经病变，在接受每天750毫克去羟肌苷的患者中发生率为34%，在接受每天500毫克去羟肌苷的患者中发生率为27%，在接受齐多夫定的患者中发生率为19%。
结论：对于先前接受齐多夫定治疗的HIV感染患者，每天500毫克去羟肌苷比继续使用齐多夫定更有效，且能改善免疫功能，但周围神经病变的风险增加。每天750毫克去羟肌苷并不比齐多夫定更有效。
Background, Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine.Methods. This multicenter, double-blind study involved 913 patients who had tolerated zidovudine for at least 16 weeks. The patients had the acquired immunodeficiency syndrome (AIDS), AIDS-related complex with less-than-or-equal-to 300 CD4 cells per cubic millimeter, or asymptomatic HIV infection with less-than-or-equal-to 200 CD4 cells per cubic millimeter. They were randomly assigned to receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per day of didanosine.Results. There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95 percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was unrelated to the duration of previous zidovudine treatment. In the two didanosine groups, there were improvements in the number of CD4 cells (P