The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial
The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial
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DOI：
10.1097/00002030-200109070-00013
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发表时间：
2001-09-07
期刊：
影响因子：
3.8
通讯作者：
Sampson, J
中科院分区：
文献类型：
--
作者：
Fisher, EJ;Chaloner, K;Sampson, J
目的：在晚期HIV病中添加到背景抗逆转录病毒疗法中的Adefovir Dipivoxil（Adefovir）的功效和安全性。设计：随机，双盲，安慰剂对照的多中心试验。 CD4细胞计数小于或等于100 x 10（6）/L或101-200 x 10（6）/L的前NADIR小于或等于50 x 10（6）/l。干预：每天口服腺或安慰剂120 mg一次。 ，CD4细胞计数，4级药物毒性，由于毒性引起的永久性药物停药。 Adefovir和252个分配的安慰剂分别为17和16死亡（P = 0.88），四个和八种经历了CMV疾病（P = 0.25）。在6个月时，Adefovir和安慰剂组中徽标血浆HIV -RNA的平均变化分别为0.09和-0.03副本/ml（P = 0.22），在12个月时为0.06和-0.02（P = 0.87）。两组之间CD4细胞计数的变化没有差异。在12个月时，Adefovir组近端肾小管功能障碍（PRTD）的累积百分比为17％，安慰剂组为0.4％（p <0.0001，日志等级测试）。在分配的Adefovir的患者中，PRTD分辨率的中位时间为15周，发病后41周没有完全解决患者。与安慰剂组相比，在阿德福维尔组中发生的药物停产更多。判断：当将adefovir添加到晚期HIV疾病中的背景抗逆转录病毒疗法中时，没有观察到病毒学或免疫学益处，并且阿德福韦与相当大的肾毒性相关。这项研究不支持在预处理的患者中使用Adefovir治疗晚期HIV疾病。 （C）2001 Lippincott Williams＆Wilkins。
Objective: Efficacy and safety of adefovir dipivoxil (adefovir) added to background antiretroviral therapy in advanced HIV disease.Design: Randomized, double-blind, placebo-controlled multicenter trial.Setting: Fifteen clinical trial units providing HIV primary care.Participants: Adults with CD4 cell count less than or equal to 100 X 10(6)/l, or 101-200 X 10(6)/l with prior nadir less than or equal to 50 X 10(6)/l.Interventions: Oral adefovir or placebo 120 mg once daily.Main outcome measures: Survival, cytomegalovirus (CMV) disease, plasma HIV-RNA, CD4 cell count, grade 4 drug toxicity, permanent drug discontinuation due to toxicity.Results: Among the 253 patients assigned adefovir and the 252 assigned placebo, respectively, 17 and 16 died (P = 0.88), and four and eight experienced CMV disease (P = 0.25). Mean change in logo plasma HIV-RNA in the adefovir and placebo groups, respectively, was 0.09 and -0.03 copies/ml at 6 months (P = 0.22) and 0.06 and -0.02 at 12 months (P = 0.87). Changes in CD4 cell counts were not different between groups. At 12 months the cumulative percent with proximal renal tubular dysfunction (PRTD) was 17% in the adefovir group and 0.4% in the placebo group (P < 0.0001, log rank test). Median time to resolution of PRTD was 15 weeks among patients assigned adefovir, and 16 lo of patients did not resolve completely 41 weeks after onset. More drug discontinuations occurred in the adefovir group than in the placebo group.Conclusions: No virologic or immunologic benefit was observed when adefovir was added to background antiretroviral therapy in advanced HIV disease, and adefovir was associated with considerable nephrotoxicity. This study does not support the use of adefovir for treatment of advanced HIV disease in pretreated patients. (C) 2001 Lippincott Williams & Wilkins.