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: 8308292
• 负责人: CHRISTOPHER J HOFFMANN
• 金额: $ 13.43万
• 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/8308292
• 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岁成年人死亡的主要原因。最近在非洲广泛采用高效抗逆转录病毒疗法治疗艾滋病毒，降低了死亡率;然而，死亡率仍然高于工业化国家。在工业化国家，高效抗逆转录病毒疗法已导致死亡原因从急性机会性感染转变为慢性疾病。在非洲，HAART的死亡原因和HAART开始后特定风险的变化尚不清楚。拟议的研究将确定HAART期间死亡的发生率和风险，随时间变化的死亡相关因素，死亡的具体原因，以及结核病和B型肝炎在死亡因果途径中的作用。该数据将用于模拟特定暴露的独立贡献，如HIV病毒血症、CD 4计数、错过访视和死亡时自行中断治疗。这些数据将有助于为公共卫生决策提供有关优化护理指南的信息，并优先考虑潜在的干预措施，以降低死亡率。拟议的研究将在南非公司HIV诊所的ART队列中回顾性进行。该研究将利用ART队列中8年的前瞻性随访，并常规获得尸检，获得约50%的死亡工人。将使用边际结构模型评估时变协变量的因果推断，并评估效应修正，以确定HAART治疗期间死亡风险随时间的变化。这项工作建立在国际项目研究所在非洲的研究经验、纵向数据分析和艾滋病毒成果的基础上。在南非完成这项研究，沿着结构化的指导和高级统计课程，将提供必要的经验和指导，以发展PI成为国际艾滋病毒治疗领域独立调查员所需的技能和技术。仔细描述长期HAART结果并确定死亡风险和原因对于优化治疗算法，制定预防策略以及在非洲实施具有成本效益的艾滋病毒护理非常重要。由于资源有限，在非洲大部分地区，实施工业化国家现有的护理水平是不可行的。然而，目前尚不清楚如何以最佳方式分配资源以取得最大成果。对死亡风险和原因的了解可有助于为改善健康和生存状况的资源分配提供信息。