Gatell J M, González-Lahoz J, Clotet B, Antunes F, Kasparova L, Gil-Aguado A, Saballs P, Santamaria J M, Podzamczer D, Miro J M, Jou A, Verdejo J, Doroana M, Thomis J
Hospital Clinic, Barcelona, Spain.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul;12(3):249-58. doi: 10.1097/00042560-199607000-00004.
This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).
本研究评估了在接受齐多夫定治疗后仍出现临床或免疫进展的患者中改用去羟肌苷的疗效。这项多中心、开放标签研究纳入了400例获得性免疫缺陷综合征（AIDS）或AIDS相关综合征（ARC）患者，这些患者已耐受齐多夫定至少12周且有临床或免疫疾病进展的迹象。他们被随机分配接受600mg/d的齐多夫定（n = 133）、500mg/d的去羟肌苷（n = 131）或200mg/d的去羟肌苷（n = 136）。主要终点是出现新的AIDS定义事件或死亡。在首次中期分析后，该研究提前终止，主要是由于两项对照研究的结果表明，改用去羟肌苷与晚期HIV-1疾病患者预后改善相关。随访的中位时间为53周。去羟肌苷500mg组、去羟肌苷200mg组和齐多夫定组的主要终点发生率分别为每100人年41、58和59例（齐多夫定与去羟肌苷500mg组相比，相对风险1.28，95%置信区间0.88 - 1.86，p = 0.19；去羟肌苷200mg与500mg组相比，相对风险1.24，95%置信区间0.85 - 1.79，p = 0.26）。在基线CD4细胞计数为100/mm³或更高的受试者中，去羟肌苷500mg组、去羟肌苷200mg组和齐多夫定组的主要终点发生率分别为每100人年8、29和25例（齐多夫定与去羟肌苷500mg组相比，相对风险2.96，95%置信区间0.91 - 9.62，p = 0.07）。生存方面未见差异。在去羟肌苷500mg组，更多患者的CD4细胞增加了50%（齐多夫定组为10%对1%，p = 0.01）且体重增加≥2.5kg（分别为2%对3%）。分配至去羟肌苷500mg组的1例患者和分配至齐多夫定组的1例患者发生了致命性胰腺炎。我们的数据表明，在有临床和实验室疾病进展证据的ARC或AIDS患者中，从齐多夫定改用目前推荐剂量的去羟肌苷可能与临床结局改善以及HIV疾病进展的替代指标改善相关。这种效应在CD4计数较高（>100/mm³）的个体中往往更大。
