AMD11070 IN HIV-POSITIVE SUBJECTS (A5210)

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。A5210是AMD11070的剂量递增、开放标签、安全性和活性研究。受试者在服药期间被允许进入GCRC。治疗将持续10天。受试者将被允许在第4、6、7、8和9天白天离开GCRC。从最后一剂AMD11070开始，将在稳定状态下获得36小时的药代动力学(PK)曲线(密集的24小时PK和30-38小时的低谷水平)，并将包括最终的PK消除曲线。根据治疗组的不同，将在第6天或第7天采集PK样本，以评估CXCR4受体饱和度并确定药物累积的特征。HIV-1RNA水平将在第0、1、2、5、7、10、14、17、30和90天进行评估。安全实验室将在0、5、10、17、30和90天获得。没有重新开始抗逆转录病毒药物治疗的受试者也将在第21天接受安全性和有效性评估。主要目标：1.确定AMD11070的几个剂量水平(起始剂量由A5191的结果确定)在10天内对携带X4嗜性病毒的HIV感染者的安全性。2.确定在AMD11070治疗10天内或在停止治疗后7天内，每个队列中具有X4嗜性病毒1log10 RLU减少的受试者的比例，并描述与X4嗜性病毒相对应的log10 RLU从基线到第10天的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A5210 is a dose escalating, open-label, safety and activity study of AMD11070. Subjects are admitted to the GCRC for the dosing period. Treatment will continue for 10 consecutive days. Subjects will be allowed daytime passes away from the GCRC on days 4,6,7,8, and 9. Thirty-six-hour pharmacokinetic (PK) profiles (intensive 24-hour PK and a trough level at Hour 30-38) will be obtained at steady state, beginning with the last dose of AMD11070, and will include terminal PK elimination profiles. Trough PK collections will be drawn on day 6 or 7, depending on the treatment group, to assess CXCR4 receptor saturation and characterize drug accumulation. HIV-1 RNA levels will be assessed on Days 0, 1, 2, 5, 7, 10, 14, 17, 30 and 90. Safety labs will bevobtained at Days 0, 5, 10, 17, 30, and 90. Subjects who have not restarted antiretroviral medications will also be assessed for safety and efficacy on Day 21. Primary Objectives: 1. To determine the safety of several dose levels of AMD11070 (with the starting dose determined by the results of A5191) administered over 10 days to HIV-infected subjects who harbor X4-tropic virus. 2. To determine the proportion of subjects per cohort who have a >1 log10 rlu reduction in X4-tropic virus during 10 days of AMD11070 treatment or in the 7 days following treatment discontinuation, and to describe changes from baseline to Day 10 in log10 rlu corresponding to X4-tropic virus.