CAUSES OF AND ASSOCIATIONS WITH DEATH DURING LONG TERM HAART IN AFRICA

非洲长期 HAART 期间死亡的原因及其相关性

• 批准号: 8102047
• 负责人: CHRISTOPHER J HOFFMANN
• 金额: $ 13.42万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8102047
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Adult; Adverse effects; Africa; African; Age; Algorithms; Area; Autopsy; CD4 Lymphocyte Count; Cardiovascular Diseases; Caring; Categories; Cause of Death; Cessation of life; Chronic Disease; Chronic Hepatitis B; Clinic; Clinical; Cohort Studies; Collaborations; Country; Cox Proportional Hazards Models; Data; Data Analyses; Developed Countries; Gold; Guidelines; HIV; Health; Hepatitis B; Hepatitis B Virus; Highly Active Antiretroviral Therapy; Incidence; Individual; Infection; International; Interruption; Intervention; Knowledge; Lead; Left; Liver diseases; Malignant Neoplasms; Mentorship; Modeling; Modification; Monitor; Opportunistic Infections; Outcome; Pathway interactions; Patients; Plant Roots; Population; Prevention strategy; Public Health; RNA; Records; Recovery; Regimen; Reporting; Research; Research Personnel; Resource Allocation; Resources; Risk; Risk Factors; Role; Slide; South Africa; Southern Africa; Structural Models; Structure; Techniques; Testing; Time; Tuberculosis; Viremia; Visit; Vital Status; Work; Workplace; aged; base; cohort; cost effective; experience; follow-up; improved; insight; mortality; programs; prospective; sex; skills; statistics; success; therapy outcome; time interval

DESCRIPTION (provided by applicant): HIV is the leading cause of death among adults aged 15-64 in Africa. Recent wide-spread introduction of highly active antiretroviral therapy (HAART) to treat HIV in Africa has reduced mortality; however, mortality rates remain higher than in industrialized countries. In industrialized countries, HAART has lead to a shift in causes of death from acute opportunistic infections to chronic diseases. Causes of mortality on HAART and changes in specific risks over duration from HAART initiation are unknown in Africa. The proposed study will determine incidence and risks for mortality during HAART, changing factors associated with death over time, specific causes of death, and the role of both TB and hepatitis B in causal pathways to death. This data will be used to model the independent contributions of specific exposures such as HIV viremia, CD4 count, missed visits, and self initiated treatment interruption on death. These data will help to inform public health decisions regarding optimization of care guidelines and to prioritize potential interventions to reduce mortality. The proposed research will be conducted retrospectively within an ART cohort based in company HIV clinics in South Africa. The research will utilize 8 years of prospective follow-up in the ART cohort and routinely obtained autopsies, obtained for approximately 50% of workers who die. Marginal structural models will be used to assess causal inference for time varying covariates and effect modification will be assessed to identifying changing risks for death over time on HAART. This work builds on the PIs experience with research in Africa, longitudinal data analysis, and HIV outcomes. Completing this research in South Africa, along with structured mentorship and advanced statistics courses, will provide the necessary experience and guidance to develop skills and techniques needed for the PI to emerge as an independent investigator in the area of international HIV treatment. Careful description of long-term HAART outcomes and identification of risks for and causes of death is important to optimize treatment algorithms, develop prevention strategies, and implement cost-effective HIV care in Africa. Because of limited resources implementing a level of care as exists in industrialized countries is not feasible in most of Africa. However, the optimum approach to allocating resources to maximize outcomes is currently unclear. Knowledge of risks for and causes of mortality can contribute to informing resource allocation aimed at improving health and survival.

描述（由申请人提供）：艾滋病毒是非洲15-64岁成年人的主要死亡原因。最近广泛引入了高度活跃的抗逆转录病毒疗法（HAART）以治疗非洲的HIV死亡率降低。但是，死亡率仍然高于工业化国家。在工业化国家，HAART导致死亡原因从急性机会主义感染转变为慢性疾病。在非洲，HAART启动期间因HAART死亡的原因和特定风险的变化在非洲尚不清楚。拟议的研究将确定HAART期间死亡率的发病率和风险，随着时间的流逝而变化的因素，特定的死亡原因以及结核病和丙型肝炎在因果关系死亡途径中的作用。该数据将用于模拟特定暴露的独立贡献，例如HIV病毒血症，CD4计数，访问访问和自我引发的治疗中断。这些数据将有助于告知有关优化护理指南的公共卫生决策，并确定潜在的干预措施以降低死亡率。拟议的研究将在南非公司艾滋病毒诊所的一家艺术群体中进行追溯性。这项研究将利用ART队列中的8年的前瞻性随访，并经常进行尸检，该尸检大约为死亡的工人中的大约50％。边际结构模型将用于评估时间变化的协变量的因果推断，并将评估效果修改以确定随着时间的流逝而随着时间的流逝而变化的死亡风险。这项工作是基于非洲研究，纵向数据分析和HIV结果的PIS经验的基础。在南非完成这项研究，以及结构化的指导和高级统计课程，将提供必要的经验和指导，以开发PI成为国际HIV治疗领域的独立研究者所需的技能和技术。仔细描述长期的HAART结果以及对死亡的风险和原因的识别对于优化治疗算法，制定预防策略并在非洲实施具有成本效益的HIV护理非常重要。由于资源有限，在非洲大部分地区实施了一定程度的护理，因此在工业化国家中存在不可行。但是，目前尚不清楚分配资源以最大化结果的最佳方法。对死亡率的风险和原因的知识可能有助于告知旨在改善健康和生存的资源分配。