HAART

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。主要目标（治疗药物监测[TDM]）确定适合进行药物干预的患者人群（基于专家小组的建议），并确定需要TDM干预的预测因素。2. 开发和验证算法和临床相关的切入点，以解释在TDM调整后实现所需的药理学措施所决定的药理学参数。次要目标（治疗药物监测[TDM]）定义推荐了PK干预措施的患者比例，其主要提供者实施了建议，并描述为什么不遵循建议。2. 通过反复血浆浓度评估，确定TDM改变后达到预期药理学效果的患者比例。3. 探讨Cmin/IC50比值作为病毒学成功的预测因子，以及作为监测和改变药物方案的指标。4. 确定治疗药物监测（TDM）在开始或改变抗逆转录病毒治疗的患者改善HIV RNA减少方面的独立价值（从依从性干预）。5. 确定血浆ARV浓度与不良事件（包括空腹脂质浓度）之间的相关性，并观察TDM是否可用于减少抗逆转录病毒治疗的毒性。6. 观察PI和NNRTI浓度（通过重复低谷水平评估）是否在依从性干预下维持在阈值水平以上。7. 确定粘附性（通过MEMS帽装置评估）与PI和NNRTI波谷浓度之间的相关性。8. 确定TDM对CD4从基线变化的影响。9. 探索其他药效学标志物，如AUC、Cmax与敏感性值（IC50或IC90）结合作为病毒学反应的预测因子。10. 探讨免疫在维持art诱导的病毒抑制中的作用。主要目标（坚持）为了确定一个简短（5个疗程）的临床培训干预，包括除了心理教育成分外的惰性药物治疗方案的实践试验，是否优于单独的心理教育成分的干预，以及在改善HAART的依从性方面优于“常规临床护理”。2. 目的：确定培训干预是否能有效地维持12个月的药物依从性。3. 评估培训干预的效果，以及总体上的依从性，对临床结果的病毒学测量（例如，改善依从性是否降低病毒载量并增加CD4计数？）什么程度的不良依从性与病毒耐药性的发展有关？为了进一步检查依从性和临床结果之间的关系，研究人员将使用数据校准这种关系的结构模型，以预测治疗开始前患者的临床结果轨迹。次要目标（坚持）为了确定，在培训干预的背景下，坚持惰性药物治疗方案是否预示着坚持HAART治疗。2. 确定阻碍或促进依从性的社会心理、神经心理和环境因素，以及对抗逆转录病毒治疗的态度和信念。

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.