PHARMACOKINETICS AND ANTIRETROVIRAL RESISTANCE TESTING

点击翻译按钮获取中文摘要

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.