Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - A randomized, double-blind, placebo-controlled trial
Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - A randomized, double-blind, placebo-controlled trial
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DOI：
10.7326/0003-4819-124-12-199606150-00001
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发表时间：
1996-06-15
影响因子：
39.2
通讯作者：
Pettinelli, C
中科院分区：
文献类型：
--
作者：
DAquila, RT;Hughes, MD;Pettinelli, C
目的：研究在齐多夫定和去羟肌苷的联合治疗中加入第三种人类免疫缺陷病毒1型（HIV-1）逆转录酶抑制剂奈韦拉平。（获得性免疫缺陷综合征）临床试验单位。患者：398名成人HIV-1感染者，CD4（+）T淋巴细胞/mm（3）≤ 350，既往接受核苷类药物治疗6个月以上。1）奈韦拉平或安慰剂（200 mg/d，持续2周，然后400 mg/d）和2）开放标签齐多夫定（600 mg/d）和去羟肌苷（对于体重大于或等于60 kg的患者，400 mg/d）。对所有患者随机抽取的血浆样本中的CD4（+）T淋巴细胞计数、至首次HIV-1疾病进展事件或死亡的时间、不良事件和奈韦拉平水平进行测量。在一半的研究中心，对入组患者的血浆HIV-1 RNA水平、外周血单个核细胞中的HIV-1感染性滴度、血清p24抗原水平以及齐多夫定和去羟肌苷的血浆水平进行了测定。研究治疗48周后，分配至三联治疗方案的患者（奈韦拉平、齐多夫定和去羟肌苷）的平均绝对CD4细胞计数高18（95% CI，7%-29%; P = 0.001），外周血单核细胞中平均感染性HIV-1滴度降低0.32 log（10）（CI，0.05 - 0.59 log（10）感染单位/百万细胞; P = 0.023），平均血浆HIV-1 RNA水平降低0.25 log（10）（CI，0.03至0.48 log（10）RNA拷贝/mL; P = 0.028）比分配到双重组合方案（齐多夫定和去羟肌苷）的患者。严重皮疹在分配接受三联治疗的患者中更常见（9%比2%; P = 0.002）。两组之间的疾病进展风险没有差异（三联用药组的相对危险度为1.24 [CI为0.75 - 2.06]; P> 0.2），尽管该研究仅具有中等的把握度来检测主要差异。在齐多夫定和去羟肌苷的基础上加入奈韦拉平，长期免疫学和病毒学治疗的影响，并与严重皮疹的患者研究，谁有广泛的以前的治疗。这些结果支持1）继续开发两种以上抗逆转录病毒药物的组合，以增加和延长HIV-1抑制; 2）奈韦拉平在联合治疗方案中的潜在效用。
Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine.Design: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units.Patients: 398 adults who had HIV-1 infection, had 350 or fewer CD4(+) T lymphocytes/mm(3), and had had more than 6 months of previous nucleoside therapy.Intervention: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing greater than or equal to 60 kg).Measurements: CD4(+) T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA; HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites.Results: After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% CI, 7% to 29%; P = 0.001), a 0.32 log(10) lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (CI, 0.05 to 0.59 log(10) infectious units per million cells; P = 0.023), and a 0.25 log(10) lower mean plasma HIV-1 RNA level (CI, 0.03 to 0.48 log(10) RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [CI, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference.Conclusions: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens.