PHARMACOKINETICS AND ANTIRETROVIRAL RESISTANCE TESTING

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。近年来，监测艾滋病毒感染患者体内抗逆转录病毒浓度的概念得到了广泛关注。然而，关于实施药物水平监测的最佳方法仍然存在有效的担忧。此外，在给药时必须考虑病毒的药物敏感性，特别是在挽救性治疗中。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，以帮助临床医生为抢救治疗患者选择最佳方案。这种方法称为概率估计，可以潜在地确定各种抗逆转录病毒药物达到IC50以上低谷水平的概率。本应用程序的目标是：1)收集新型抗逆转录病毒治疗方案的PK数据；2)利用这些数据模拟必要的浓度时间曲线；3)前瞻性地评估这种新的概率估计方法。为了实现这一目标，将在接受挽救性治疗的患者中评估选择新方案（6-8名受试者/方案）的PK。所有受试者都将进行PK评估，然后根据这些PK数据得出模拟浓度-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进行前瞻性的概率估计。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治疗经验丰富的患者。

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.