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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。主要目标（治疗药物监测[TDM]）1。定义适合药理干预的患者人群（基于专家小组建议），并定义了预测TDM干预需求的因素。 2。开发和验证算法和临床相关的切点，以解释药理学参数，这是通过在TDM调整后实现所需的药理学测量来确定的。 次要目标（治疗药物监测[TDM]）1。定义建议使用PK干预措施的患者的比例，并且其主要提供者实现了建议，并描述了为什么不遵循建议。 2。定义实施TDM变化的患者的比例，这些患者通过反复的血浆浓度评估了所需的药理作用。 3。探索CMIN/IC50比例作为病毒学成功的预测指标，并作为用于监测和改变药物方案的度量。 4。确定治疗药物监测（TDM）的独立值（根据依从性干预）改善了启动或改变ARV治疗的患者的HIV RNA减少。 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，并查看TDM是否可以最大程度地减少抗逆转录病毒疗法的毒性。 6。查看PI和NNRTI浓度（如重复的谷水平评估）是否在依从性干预措施下保持在阈值水平以上。 7。确定粘附之间的相关性，如MEMS盖设备评估，PI和NNRTI凹槽浓度。 8。确定TDM对CD4从基线变化的影响。 9。探索其他药效标记，例如AUC，CMAX与易感性值（IC50或IC90）结合使用，作为病毒学反应的预测指标。 10。研究免疫在维持艺术诱导的病毒抑制中的作用。 主要目标（依从性）1。确定简短的（5个会话），基于诊所的培训干预措施，包括对惰性药物治疗方案的练习试验，除了心理教育成分外，是否优于与心理教育成分的干预，以及”通常的临床护理“改善了对Haart的依从性。 2。确定训练干预是否有效维持12个月的改进药物依从性。 3。为了评估训练干预措施的影响以及一般的依从性，对临床结局的病毒学测量方法（例如，改善的依从性是否减少了病毒载量并增加了CD4计数？依从性的依从性与病毒耐药性的发展有关？） 。为了进一步研究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，以预测治疗开始之前患者的临床结果轨迹。 次要目标（依从性）1。确定在训练干预的背景下，遵守惰性药物方案是否预测了对Haart的依从性。 2。确定会阻碍或促进依从性的社会心理，神经心理学和情境因素以及对抗逆转录病毒疗法的态度和信念。