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: 7229276
• 负责人: Bryan Lau
• 金额: $ 13.5万
• 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/7229276
• 关键词: AIDS epidemiology; Acquired Immunodeficiency Syndrome; Address; Anti-Retroviral Agents; Area; Attention; 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; Count; Creatinine; Data; Depth; Development; 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; Range; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Resistance; Risk; Risk Factors; Schedule; Scientist; Serum Albumin; Statistical Methods; Structure; Therapeutic; Time; Treatment Protocols; United States; Viral; Visit; base; career; cohort; experience; health care service utilization; improved; modifiable risk; mortality; prognostic; programs; response; time interval

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K01奖的申请，重点是与NIAID的目标（NOT-AI-04-033）特别相关，即促进年轻科学家在传染病和艾滋病流行病学和结果研究方面的职业发展。Bryan Lau博士将应用严格的流行病学和生物统计学方法来解决与当前艾滋病毒护理高度相关的三个主要研究目标。虽然有效的治疗方法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果变化的关注仍然存在。目前的艾滋病毒治疗指南建议在CD4细胞计数低于200个/ μ l时开始HAART治疗方案，并考虑在200至350个细胞/ μ l之间开始。尽管有治疗指南，但超过200个细胞/ μ l的个体仍会进展为艾滋病和死亡。临床队列研究可能有助于解决与治疗优化和因治疗而发生的死亡率变化有关的问题。然而，临床队列研究有非结构化的访问时间表，允许个人潜在地自我选择更频繁地使用医疗保健，而“经典”队列个体在设定的时间间隔内进行跟踪。尽管经典的队列研究设计可能无法在研究访问之间设置间隔，因为间隔是任意的，而不是基于医疗保健需求。该研究项目的目标是：1)确定CD4计数和HIV RNA水平以外的生物标志物是否有可能用于进一步针对需要开始治疗的个体的靶向治疗，以及这些标志物是否可以用于监测治疗反应；2)量化自引入有效疗法以来病因特异性死亡风险的变化；3)比较基于区间的（经典）和基于临床的队列研究结果的潜在差异。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：约翰霍普金斯大学艾滋病毒临床队列和艾滋病静脉注射经验链接（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开始治疗并监测治疗效果。此外，确定特定原因死亡率的变化可能有助于确定需要注意的潜在领域，这些领域可能传统上被认为与艾滋病毒无关。K01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，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，并将这些学科融入到富有成效和独立的研究生涯中。