Kahn J O, Lagakos S W, Richman D D, Cross A, Pettinelli C, Liou S H, Brown M, Volberding P A, Crumpacker C S, Beall G
San Francisco General Hospital, Calif. 94110.
N Engl J Med. 1992 Aug 27;327(9):581-7. doi: 10.1056/NEJM199208273270901.
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.
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 milliliter, or asymptomatic HIV infection with less than or equal to 200 CD4 cells per cubic milliliter. 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.
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 less than 0.001 for both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005 in the 750-mg group), as compared with the zidovudine group.
Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease.
虽然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。
这项多中心、双盲研究纳入了913名对齐多夫定耐受至少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细胞少于或等于300个的AIDS相关综合征，或每立方毫米CD4细胞少于或等于200个的无症状HIV感染。他们被随机分配接受每日600毫克齐多夫定、每日750毫克去羟肌苷或每日500毫克去羟肌苷治疗。
在分配接受每日500毫克去羟肌苷治疗的298名受试者中，新的AIDS定义事件和死亡人数明显少于继续接受齐多夫定治疗的受试者（相对风险，1.39；95%置信区间，1.06至1.82；P = 0.015）。使用750毫克去羟肌苷时，与齐多夫定相比没有明显益处（相对风险，1.10；95%置信区间，0.86至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。与齐多夫定组相比，在两个去羟肌苷组中，CD4细胞数量（两组P均小于0.001）和p24抗原水平（500毫克组P = 0.03；750毫克组P = 0.005）均有所改善。
将治疗从齐多夫定改为每日500毫克去羟肌苷似乎能减缓HIV疾病的进展。
