HAART

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。主要目标(治疗药物监测[TDM])1.确定适合进行药物干预的患者群体(基于专家小组的建议)，并确定预测需要进行TDM干预的因素。2.开发和验证用于解释药理参数的算法和临床相关切入点，这些参数由TDM调整后所需药理措施的实现情况确定。次要目标(治疗药物监测[TDM])1.确定推荐进行PK干预的患者和其主要提供者执行该建议的比例，并描述为什么不遵循建议。2.确定实施TDM改变的患者达到通过重复血浆浓度评估的预期药理效果的比例。3.探讨Cmin/IC50比值作为病毒学成功的预测指标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，以及TDM是否可用于将抗逆转录病毒治疗的毒性降至最低。6.观察依从性干预措施后，PI和NNRTI浓度(通过重复谷底水平评估)是否维持在阈值水平以上。7.确定由MEMS CAP设备评估的粘附性与PI和NNRTI谷浓度之间的相关性。8.确定TDM对基础状态下CD_4细胞变化的影响。9.探讨其他药效学标志物，如AUC、Cmax结合药敏值(IC50或IC90)作为病毒学应答的预测因子。10.探讨免疫在维持ART诱导的病毒抑制中的作用。主要目标(依从性)1.确定在改善HAART依从性方面，简短的(5期)以临床为基础的培训干预是否优于单独使用心理教育成分的干预，以及“常规临床护理”，其中包括对惰性药物治疗方案的实践试验。2.确定培训干预是否有效地在12个月期间保持改善的服药依从性。3.评估训练干预和一般依从性对临床结果的病毒学测量的影响(例如，依从性的改善是否降低了病毒载量并增加了CD4计数？依从性差的程度与病毒抵抗力的发展有关？)为了进一步检验依从性和临床结果之间的关系，研究人员将使用数据来校准这种关系的结构模型，以在治疗开始之前预测患者的临床结果轨迹。次要目标(依从性)1.在训练干预的背景下，确定坚持惰性药物治疗方案是否预示着坚持HAART。2.查明阻碍或促进坚持治疗的心理社会、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。

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.