Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial
Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial
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DOI：
10.1097/00002030-200310170-00001
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发表时间：
2003-10-17
期刊：
影响因子：
3.8
通讯作者：
Hirschel, B
中科院分区：
文献类型：
--
作者：
Ananworanich, J;Nuesch, R;Hirschel, B
背景：为了降低高效抗逆转录病毒疗法(HAART)的成本和副作用，正在对计划中的治疗中断进行评估。在Staccato研究中，600名成功接受HAART的患者被随机分为继续治疗、CD4引导治疗或一周治疗，或一周治疗，休息一周。结果：在36名可评估的患者中，19名(53%)在结束治疗的一周内连续两次HIV RNA浓度&500拷贝/毫升，被归类为病毒学失败。大多数失败者服用了地达诺辛、司他夫定、沙奎那韦和利托那韦(11名患者)。在这些患者中，没有证据表明存在耐药突变，血浆沙奎那韦水平在预期范围内。三个核苷酸失败的患者中有两个发生了耐药性突变，但仍然对重新引入三核苷酸治疗有反应。两名服用奈韦拉平的患者中有一名和八名服用法韦伦兹的患者中的一名也失败了。两者在失败时都有耐药突变，但都没有基线。结论：Staccato研究中测试的1周开始1周休息计划显示出不可接受的高失败率，因此被终止。(C)2003年，里平科特·威廉姆斯·威尔金斯。
Background: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration.Methods: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm.Results: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline.Conclusions: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated. (C) 2003 Lippincott Williams Wilkins.