Comparative effectiveness of tailored HIV treatment plans and mortality

定制的艾滋病毒治疗计划和死亡率的比较效果

• 批准号: 9270331
• 负责人: Jessie Edwards
• 金额: $ 13.16万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9270331
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Address; Adult; Aging; Award; Bayesian Analysis; Bayesian Method; Biometry; Calendar; Caring; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cessation of life; Characteristics; Clinical; Clinical Research; Collection; Comorbidity; Complement; Complex; Consensus; Coupled; Data; Data Sources; Diagnosis; Early treatment; Epidemiologic Methods; Epidemiology; Exposure to; Foundations; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; Information Centers; Instruction; Integrase Inhibitors; International; Life Expectancy; Logic; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Modeling; Modernization; Outcome; Patients; Pharmacotherapy; Population; Probability; Recording of previous events; Regimen; Reporting; Research; Research Personnel; Risk; Risk Estimate; Sample Size; Site; Statistical Methods; Structural Models; System; Tablets; Techniques; Testing; Time; Toxic effect; Training; Work; antiretroviral therapy; base; career development; clinical care; cohort; comparative; comparative effectiveness; demographics; design; experience; high dimensionality; improved; individual patient; individualized medicine; insight; member; mortality; personalized medicine; precision medicine; semiparametric; symposium; theories; training project; treatment planning; treatment strategy

PROJECT SUMMARY The overall goal of this K01 application is to optimize clinical care decisions for people living with HIV. Specifically, this project will explore how cause-specific mortality among people with HIV has changed as treatment has become more effective and how the choice of antiretroviral therapy (ART) regimen can be tailored or personalized based on patient characteristics to improve survival. Since 2012, many patients have initiated regimens containing integrase inhibitors, but overall and cause-specific mortality for patients on these regimens is uncertain. In addition, the comparative effectiveness of the recommended integrase inhibitor containing regimens for patients with disparate characteristics and treatment histories has yet to be explored. Standard epidemiologic methods are insufficient to optimize HIV treatment plans because treatment plans and tailoring strategies are high dimensional, resulting in sparse data and unstable inference in many data sources, particularly when treatment plans can change over time. The goal of this career development project is to train the recipient to perform comparative effective research in settings with many exposure plans and outcomes. Research aims of this project are to 1) Compare the cause-specific mortality risks among patients with HIV in the US across three time periods representing the triple drug therapy era, the single tablet era, and the integrase inhibitor era (i.e., 2000 – 2005, 2006 – 2012, 2013 – 2018); and 2) Estimate all-cause mortality risks under strategies to optimize selection of an integrase inhibitor containing regimen based on treatment history and patient characteristics. To address these aims in cohort data, the training component of this grant focuses on building expertise in semi-Bayesian semiparametric inference in the context of HIV research. Specifically, training aims include 1) Instruction in statistical techniques to improve inference for tailored treatment plans in high dimensional settings; 2) Training in applied HIV epidemiology; and 3) Experience and preliminary results necessary to prepare an R01 application in the fourth year of this award. The training aims will be achieved through rigorous coursework in advanced biostatistics, mentored and collaborative research, and conference participation. Research aims will be conducted using data from the Centers for AIDS Research Network of Integrated Clinical Systems, which includes over 30,000 HIV-seropositive adults engaged in clinical care from January 1, 1995 to the present at 8 US sites. The project will use semiparametric methods to account for missing causes of death and will estimate all parameters describing cause-specific mortality accounting for competing causes of death. Aim 2 will use Bayesian penalization techniques to estimate the causal effects of tailored treatment plans using marginal structural models and the parametric g-formula. This project will address an urgent need to optimize treatment plans in the current treatment era with an aging HIV-positive population with increasing comorbidities.

项目概要 该 K01 应用程序的总体目标是优化 HIV 感染者的临床护理决策。 具体来说，该项目将探讨艾滋病毒感染者的特定原因死亡率是如何变化的 治疗变得更加有效，以及如何选择抗逆转录病毒治疗（ART）方案 自 2012 年以来，许多患者已经根据患者特征进行定制或个性化治疗以提高生存率。 启动了含有整合酶抑制剂的治疗方案，但这些治疗方案患者的总体死亡率和特定原因死亡率 此外，推荐的整合酶抑制剂的相对有效性尚不确定。 针对具有不同特征和治疗史的患者的治疗方案仍有待探索。 标准流行病学方法不足以优化艾滋病毒治疗计划，因为治疗计划和 剪裁策略是高维的，导致许多数据源中数据稀疏且推理不稳定， 特别是当治疗计划可能随着时间的推移而改变时。该职业发展项目的目标是培训。 接收者在具有许多暴露计划和结果的环境中进行相对有效的研究。 该项目的研究目的是 1) 比较不同国家和地区的艾滋病病毒感染者的特定原因死亡风险 美国经历了三个时期，分别是三联药物治疗时代、单一药片时代和 整合酶抑制剂时代（即2000年至2005年、2006年至2012年、2013年至2018年）； 根据治疗史优化选择含有整合酶抑制剂的方案的策略 为了解决队列数据中的这些目标，本次拨款的培训部分重点关注。 在艾滋病毒研究的背景下建立半贝叶斯半参数推理的专业知识。 培训目标包括 1) 统计技术指导，以改进对定制治疗计划的推断 高维度环境；2) 应用艾滋病毒流行病学培训；以及 3) 经验和初步结果 需要在该奖项的第四年准备 R01 申请 培训目标将实现。 通过严格的高级生物统计学课程、指导和合作研究以及会议 研究目标将使用来自艾滋病研究网络中心的数据进行。 综合临床系统，包括超过 30,000 名 HIV 血清阳性成年人，参与临床护理 1995年1月1日至今在美国8个站点该项目将采用半参数方法进行核算。 缺少死亡原因，并将估计描述特定原因死亡率的所有参数 目标 2 将使用贝叶斯惩罚技术来估计相互竞争的死亡原因。 该项目将使用边际结构模型和参数 g 公式定制治疗计划。 解决当前治疗时代优化艾滋病毒阳性老年患者治疗计划的迫切需要 合并症日益增多的人群。