PHARMACOKINETICS AND ANTIRETROVIRAL RESISTANCE TESTING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。近年来，监测艾滋病毒感染者体内抗逆转录病毒药物浓度的概念得到了加强。然而，对实施药物水平监测的最佳方法仍然存在合理的关切。此外，在抗逆转录病毒药物给药时，必须考虑病毒药物敏感性，特别是在挽救治疗中。一种监测药物治疗的新方法描述了一种整合药代动力学（PK）和表型信息的方法，以帮助临床医生为挽救治疗患者选择最佳方案。这种称为概率估计的方法可以潜在地确定各种抗逆转录病毒药物达到高于IC 50的谷水平的概率。本申请的目的是：1）收集新型抗逆转录病毒治疗方案的PK数据; 2）使用这些数据模拟必要的浓度-时间曲线，3）前瞻性评价这种新型概率估计方法。为此，将在接受挽救治疗的患者中评价选定新型治疗方案（6-8例受试者/治疗方案）的PK。所有受试者将接受PK评价，随后将根据这些PK数据推导出模拟浓度-时间曲线。然后将这些模拟浓度和病毒易感性信息结合起来，以前瞻性地探索概率估计。这项工作的长期目标是为临床医生提供一个额外的工具来管理有治疗经验的患者。

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. The concept of monitoring antiretroviral concentrations in patients with HIV-infection has gained momentum over recent years. However, valid concerns remain regarding optimal methods for implementing drug level monitoring. In addition, viral drug susceptibility must be taken into consideration when dosing antiretrovirals, especially in salvage therapy. A novel approach for monitoring drug therapy describes a method of integrating pharmacokinetic (PK) and phenotypic information to assist clinicians in choosing optimal regimens for salvage therapy patients. This approach, termed probability estimations, can potentially determine the probability of achieving trough levels above the IC50 for various antiretrovirals. The goals of this application are: 1) to collect PK data on novel antiretroviral regimens; 2) use these data to simulate the necessary concentration time curves, and 3) prospectively evaluate this novel probability estimations approach. To accomplish this, PK of select novel regimens (6-8 subjects/regimen) will be evaluated in patients receiving salvage therapy. All subjects will undergo PK evaluations, and simulated concentration-time curves will be subsequently derived from these PK data. These simulated concentrations and viral susceptibility information will then be combined to prospectively explore probability estimations. The long-term goal of this work is to provide clinicians with an additional tool to manage treatment experienced patients.