ACTG 320: A Randomized, Double-Blind, Phase III Study of Indinavir Sulfate (IDV) with Open-Label ZDV or Stavudine (d4T) and Lamivudine (3TC) in Subjects with HIV Infection with < or = 200 CD4 Cell Counts and > or = 3 Months of Prior Zidovudine (ZDV)

Background: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. Methods: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. Stavudine could be substituted for zidovudine. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. Results: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine (or stavudine), and lamivudine (6 percent) than with zidovudine (or stavudine) and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P 0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P 0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. Conclusions: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine. (N Engl J Med 1997;337:725-33.)

研究背景：在两种核苷类似物（nucleoside analogues）治疗方案基础上加用蛋白酶抑制剂（protease inhibitor）治疗人类免疫缺陷病毒1型（HIV-1）感染的疗效与安全性尚未明确。本研究针对既往接受过齐多夫定（zidovudine）治疗的HIV感染成人患者，对比了在齐多夫定（zidovudine）与拉米夫定（lamivudine）基础上加用蛋白酶抑制剂茚地那韦（indinavir），与仅使用两种核苷类药物的治疗方案的差异。
研究方法：共纳入1156例既往未接受过拉米夫定（lamivudine）或蛋白酶抑制剂（protease inhibitor）治疗的患者，按CD4细胞计数进行分层（≤50个/立方毫米 vs. 51~200个/立方毫米），并随机分配至两种每日给药方案之一：方案一为齐多夫定（zidovudine）600mg联合拉米夫定（lamivudine）300mg；方案二为上述核苷类方案基础上加用茚地那韦（indinavir）2400mg。司他夫定（stavudine）可作为齐多夫定（zidovudine）的替代用药。本研究的主要终点为出现获得性免疫缺陷综合征（AIDS）或死亡的时间。
研究结果：联合茚地那韦（indinavir）、齐多夫定（zidovudine）（或司他夫定（stavudine））与拉米夫定（lamivudine）的治疗组中，疾病进展至AIDS或死亡的患者比例（6%）低于仅使用齐多夫定（zidovudine）（或司他夫定（stavudine））与拉米夫定（lamivudine）的对照组（11%；估计风险比0.50，95%置信区间0.33~0.76；P=0.001）。两组的死亡率分别为1.4%与3.1%（估计风险比0.43，95%置信区间0.19~0.99；P=0.04）。两种CD4细胞分层亚组的治疗获益相似。CD4细胞与血浆HIV-1 RNA的应答变化趋势与临床结局一致。
研究结论：对于既往曾接受齐多夫定（zidovudine）治疗、CD4细胞计数≤200个/立方毫米的HIV-1感染患者，相较于仅使用齐多夫定（zidovudine）与拉米夫定（lamivudine）的方案，茚地那韦（indinavir）联合齐多夫定（zidovudine）与拉米夫定（lamivudine）的治疗方案可显著延缓HIV-1疾病进展。（《新英格兰医学杂志（N Engl J Med）》1997；337：725-33.）