Biomarkers, Therapy, and Mortality in the Evolving HIV Epidemic

不断演变的艾滋病毒流行病中的生物标志物、治疗和死亡率

• 批准号: 7804576
• 负责人: Bryan Lau
• 金额: $ 13.17万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804576
• 关键词: AIDS epidemiology; Acquired Immunodeficiency Syndrome; Address; Anti-Retroviral Agents; Area; Attention; Biological Markers; Biological Markers; Biometry; Biostatistical Methods; CD4 Lymphocyte Count; Caring; Cause of Death; Cells; Cessation of life; Clinic; Clinical; Clinical Markers; Cohort Studies; Communicable Diseases; Complex; Creatinine; Data; Discipline; Disease Progression; Doctor of Philosophy; Effectiveness; Epidemic; Epidemiology; Fostering; Frequencies; Goals; Guidelines; HIV; HIV-1; Healthcare; Hemoglobin; Highly Active Antiretroviral Therapy; Immunologics; Individual; Intravenous; Knowledge; Link; Lymphocyte; Lymphocyte Count; Measurement; Mentored Research Scientist Development Award; Mentors; Methods; Monitor; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Outcome; Outcomes Research; Patient Monitoring; Patients; Population; Principal Investigator; Public Health; Quality of life; RNA; Regimen; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Resistance; Risk; Risk Factors; Schedule; Scientist; Serum Albumin; Statistical Methods; Structure; Therapeutic; Time; United States; Viral; Visit; base; career; career development; cohort; effective therapy; experience; health care service utilization; high risk; improved; modifiable risk; mortality; prognostic; programs; response; time interval; treatment response

DESCRIPTION (provided by applicant): This is an application for a 5-year K01 award from NIAID with an emphasis particularly relevant to NIAID's goals (NOT-AI-04-033) of fostering the career development of young scientists in infectious diseases and AIDS epidemiology and outcomes research. Bryan Lau, Ph.D., will apply rigorous epidemiological and biostatistical methods to address three major research aims that are highly relevant to the current HIV care. While effective therapies have greatly reduced the mortality and morbidity due to HIV, current concerns regarding the optimization of therapy and the changes in mortality outcomes remain. Current therapeutic guidelines for HIV recommend initiating a HAART regimen at CD4 counts below 200 cells/uL and consider nitiating between 200 to 350 cells/uL Despite the therapeutic guidelines, individuals above 200 cells/uL do progress to AIDS and death. Clinical cohort studies may be useful for addressing questions related to optimization of therapy and the changes in mortality that have occurred due to therapy. However, clinical cohort studies have unstructured visit schedules allowing for individuals to potentially self-select for more frequent health-care utilization whereas the "classical" cohort individuals are followed at set time-intervals. Although classical cohort study designs may not capture the fullest extent of the information with a set interval between study visits as the interval is arbitrary and not based on health care needs. The goal of this research project is to: 1) determine whether biological markers other than CD4 counts and HIV RNA levels could potentially be used to further target therapy towards individuals that need to initiate treatment and whether these markers may be utilized in monitoring treatment response; 2) quantify the changes in cause-specific mortality risk since the introduction of effective therapies; and 3) to compare potential differences in results between interval-based (classical) and clinic-based cohort studies. These goals will be accomplished by utilizing two ongoing HIV cohorts: the Johns Hopkins HIV Clinical Cohort and AIDS Link to Intravenous Experience (ALIVE). These aims have important clinical and public health significance in that individuals may be better targeted for initiation of therapy and monitored for therapy effectiveness. Additionally, identifying changes in cause-specific mortality may help identify potential areas that require attention that may not traditionally be considered HIV-related. The K01 will provide the protected time for Dr. Lau to gain the additional mentored research experience, coursework, and involvement in HIV-related seminars and other forums that will substantially augment Dr. Lau's current research capabilities in biostatistics and epidemiology, enable him to gain an in-depth knowledge of the increasingly complex issues in clinical HIV research, and integrate these disciplines in a productive and independent research career.

描述（由申请人提供）：这是NIAID的5年K 01奖的申请，重点特别是与NIAID的目标（NOT-AI-04-033）有关，即促进传染病和艾滋病流行病学和成果研究方面年轻科学家的职业发展。Bryan Lau博士，将采用严格的流行病学和生物统计学方法，以解决三个主要的研究目标，是高度相关的目前艾滋病毒的护理。虽然有效的治疗大大降低了艾滋病毒的死亡率和发病率，但目前对治疗优化和死亡率结局变化的担忧仍然存在。目前的HIV治疗指南建议在CD 4计数低于200个细胞/uL时启动HAART方案，并考虑在200至350个细胞/uL之间启动。临床队列研究可能有助于解决与治疗优化和治疗引起的死亡率变化相关的问题。然而，临床队列研究具有非结构化的访视时间表，允许个体潜在地自我选择更频繁的医疗保健利用，而“经典”队列个体以设定的时间间隔进行随访。尽管经典队列研究设计可能无法在设定的研究访视间隔内捕获最全面的信息，因为该间隔是任意的，而不是基于医疗保健需求。该研究项目的目标是：1）确定除CD 4计数和HIV RNA水平外的生物标志物是否可能用于进一步针对需要启动治疗的个体的靶向治疗，以及这些标志物是否可用于监测治疗反应; 2）量化自引入有效治疗以来病因特异性死亡风险的变化;和3）比较基于间隔（经典）和基于临床的队列研究之间结果的潜在差异。这些目标将通过利用两个正在进行的艾滋病毒队列来实现：约翰霍普金斯艾滋病毒临床队列和艾滋病与静脉注射经验的联系（ALIVE）。这些目标具有重要的临床和公共卫生意义，因为可以更好地针对个体启动治疗并监测治疗有效性。此外，确定特定原因死亡率的变化可能有助于确定传统上可能不被认为与艾滋病毒有关的需要关注的潜在领域。K 01将为刘博士提供受保护的时间，以获得额外的指导研究经验，课程作业，并参与艾滋病毒相关的研讨会和其他论坛，这将大大增强刘博士目前在生物统计学和流行病学方面的研究能力，使他能够深入了解临床艾滋病毒研究中日益复杂的问题，并将这些学科整合到富有成效的独立研究生涯中。