HAART

高效抗逆转录病毒疗法

• 批准号: 7374245
• 负责人: CATHERINE A DIAMOND
• 金额: $ 0.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374245
• 关键词: plasma; training

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. Primary Objectives (Therapeutic Drug Monitoring [TDM]) 1. To define the population of patients for whom pharmacologic intervention would be appropriate (based on expert panel recommendation) and to define factors predictive of the need for TDM intervention. 2. To develop and validate algorithms and clinically relevant cut-points for interpretation of pharmacological parameters as determined by achievement of desired pharmacological measures after the TDM adjustment. Secondary Objectives (Therapeutic Drug Monitoring [TDM]) 1. To define the proportion of patients who have PK interventions recommended and whose primary provider implements the recommendation and to describe why recommendations are not followed. 2. To define the proportion of patients in whom a TDM change is implemented who achieve the desired pharmacological effect as assessed by repeated plasma concentrations. 3. To explore the Cmin/IC50 ratio as a predictor of virologic success and as a metric used to monitor and change drug regimens. 4. To determine the independent value (from the adherence intervention) of therapeutic drug monitoring (TDM) in improving HIV RNA reduction for patients initiating or changing ARV therapy. 5. To determine the correlation between plasma ARV concentrations and adverse events (including fasting lipid concentrations) and to see if TDM can be used to minimize toxicity of antiretroviral therapy. 6. To see if PI and NNRTI concentrations (as assessed by repeated trough levels) are maintained above threshold levels with the adherence interventions. 7. To determine the correlation between adherence, as assessed by MEMS cap devices, and PI and NNRTI trough concentrations. 8. To determine the effect of the TDM on CD4 change from baseline. 9. To explore additional pharmacodynamic markers, such as AUC, Cmax in combination with susceptibility values (IC50 or IC90) as predictors of virologic response. 10. To investigate the role of immunity in sustaining ART-induced virus suppression. Primary Objectives (Adherence) 1. To determine whether a brief (5 session), clinic-based training intervention that includes a practice trial of an inert medication regimen in addition to psychoeducational components is superior to an intervention with psychoeducational components alone, and to "usual clinical care" in improving adherence to HAART. 2. To determine whether the training intervention is effective in maintaining improved medication adherence for a period of 12 months. 3. To assess the effects of the training intervention, and adherence in general, on virologic measures of clinical outcome (e.g., Does improved adherence reduce viral load and increase CD4 count? What level of poor adherence is associated with development of viral resistance?). To further examine the relationship between adherence and clinical outcome, the investigators will use data to calibrate a structural model of this relationship to predict clinical outcome trajectory for patients before treatment begins. Secondary Objectives (Adherence) 1. To determine whether, in the context of a training intervention, adherence to the inert medication regimen predicts adherence to HAART. 2. To identify psychosocial, neuropsychological and contextual factors, as well as attitudes and beliefs about antiretroviral therapy, that impede or facilitate adherence.

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。主要目的（治疗药物监测[TDM]）1.确定适合药物干预的患者人群（基于专家小组建议），并确定预测需要TDM干预的因素。2.开发并验证用于解释药理学参数的算法和临床相关临界点，这些药理学参数是通过TDM调整后实现所需的药理学指标来确定的。 次要目的（治疗药物监测[TDM]）1.定义接受推荐PK干预的患者比例及其主要提供者执行建议的患者比例，并描述未遵循建议的原因。2.定义实施TDM变更的患者中达到预期药理学作用（通过重复血浆浓度评估）的患者比例。3.探索Cmin/IC 50比值作为病毒学成功的预测因子以及用于监测和改变药物方案的指标。4.确定治疗药物监测（TDM）在改善开始或改变ARV治疗的患者的HIV RNA减少方面的独立价值（来自依从性干预）。5.确定血浆ARV浓度与不良事件（包括空腹血脂浓度）之间的相关性，并观察TDM是否可用于最大限度地减少抗逆转录病毒治疗的毒性。6.观察依从性干预后PI和NNRTI浓度（通过重复谷水平评估）是否维持在阈值水平以上。7.确定通过MEMS帽装置评估的粘附性与PI和NNRTI谷浓度之间的相关性。8.确定TDM对CD 4较基线变化的影响。9.探索其他药效学标志物，如AUC、Cmax与敏感性值（IC 50或IC 90）联合作为病毒学应答的预测因子。10.研究免疫在维持ART诱导的病毒抑制中的作用。 主要目标（坚持）1。确定在提高HAART依从性方面，一个简短的（5次）、基于临床的培训干预（包括惰性药物治疗方案的实践试验以及心理教育成分）是否上级单独使用心理教育成分的干预，以及优于“常规临床护理”。2.确定培训干预是否能有效维持12个月的药物依从性。3.评估培训干预和一般依从性对临床结局病毒学指标的影响（例如，改善依从性是否会降低病毒载量并增加CD 4计数？什么水平的依从性差与病毒耐药性的发展相关？）。为了进一步研究依从性和临床结局之间的关系，研究人员将使用数据来校准这种关系的结构模型，以预测患者在治疗开始前的临床结局轨迹。 次要目标（依从性）1。确定在培训干预的背景下，对惰性药物治疗方案的依从性是否预示着对HAART的依从性。2.识别阻碍或促进依从性的社会心理、神经心理和背景因素，以及对抗逆转录病毒治疗的态度和信念。