Multi-level determinants of late ART initiation in sub-Saharan Africa

描述（由申请人提供）：本研究的目的是由一位新的研究者提出，旨在确定与晚期抗逆转录病毒治疗（ART）开始相关的多水平因素（即，在撒哈拉以南非洲地区，抗逆转录病毒疗法正在迅速扩大。撒哈拉以南非洲的大多数患者开始抗逆转录病毒治疗较晚，导致大量早期死亡，临床管理更加复杂和昂贵，并错过了预防艾滋病毒传播的机会。如果不更好地理解晚期ART启动的决定因素，包括上游前光标的作用（例如，由于艾滋病毒/艾滋病的流行（如诊断晚和接受护理晚），旨在实现更及时启动抗逆转录病毒治疗的努力将受到严重阻碍，该区域扩大抗逆转录病毒治疗的全部潜力将无法实现。拟议的研究将考虑与三个关键时间点相关的因素：诊断，入组护理和ART启动，因此将能够量化晚期诊断和晚期入组HIV护理对晚期ART启动的相对贡献。我们的最终目标是为干预措施的制定提供信息，以增加及时启动ART的可能性。 我们提出了一项研究，利用定量和定性的方法来检查多层次的决定因素晚开始ART（定义为CD4 <100个细胞/5L或WHO第四阶段）在开始ART的患者。这些方法包括回顾性分析现有的服务提供数据，深入的诊所和项目评估，以及病例对照研究。在目标1中，我们将检查多个层面的因素的影响-上下文（例如，城市/农村，检测覆盖率，耻辱），诊所（例如，预约遵守支持、主动测试、人员配备），以及个人（例如，年龄、性别、入职点）。我们将利用现有的数据集，这些数据集是在9个非洲国家的23个次区域的71个艾滋病毒护理和治疗诊所中收集的关于72，007名开始抗逆转录病毒治疗的人的诊所一级和个人一级服务提供数据。这些诊所和个人层面的数据将与来自全国代表性家庭调查的背景层面的数据相结合，以检查晚开始抗逆转录病毒治疗的多层面决定因素。以前的研究没有检查这些多层次的影响，在这样一个广泛的诊所和设置，也没有检查纵向数据从前ART阶段的护理导致ART启动。目标2和3，我们进行了四个诊所与历史上低，中，高率的晚期抗逆转录病毒治疗开始。我们将进行深入的临床和计划评估，以确定临床层面的推动因素/障碍，以更早地启动ART（目标2）。最后，由于对晚期ART启动的个人水平风险因素知之甚少，我们将进行详细的访谈，作为病例对照研究的一部分，检查规范和行为因素的作用（例如，健康信念，抑郁，社会支持，物质使用）通过采访360例谁开始ART晚和360名控制谁开始ART早（目标3）。这项研究的总体目标是提供关键信息，为实现更及时的ART启动战略提供信息，最终降低HIV相关的发病率和死亡率。 公共卫生相关性：美国每年花费数十亿纳税人的钱用于总统艾滋病紧急救援计划（PEPFAR），其中大部分用于撒哈拉以南非洲受灾最严重的地区。这个项目将提高我们对为什么撒哈拉以南非洲的艾滋病毒阳性者开始艾滋病毒治疗太晚的理解。这反过来又将有助于找到让人们更早接受治疗的方法，从而大大提高他们的生存机会，减少艾滋病毒感染的传播，并优化PEPFAR计划的成本效益。

DESCRIPTION (provided by applicant): The purpose of this study, proposed by a new investigator, is to determine the multi-level factors associated with late antiretroviral therapy (ART) initiation (i.e., in the advanced stages of HIV disease) in areas of sub-Saharan Africa where ART is rapidly being scaled-up. Most patients in sub-Saharan Africa initiate ART late, resulting in substantial early mortality, more complicated and costly clinical management, and missed opportunities for prevention of HIV transmission. Without a better understanding of the determinants of late ART initiation, including the role of upstream pre-cursors (e.g., late diagnosis and late enrollment into care), efforts aimed at achieving more timely ART initiation will be severely hampered, and the full potential of ART scale-up in the region will not be achieved. The proposed study will consider factors relevant to three critical time points: diagnosis, enrollment into care, and ART initiation, and thus will be able to quantify the relative contribution of late diagnosis and late enrollment to HIV care to late ART initiation. Our ultimate goal is to inform the development of interventions to increase the likelihood of timely ART initiation. We propose a study that utilizes both quantitative and qualitative methodologies to examine the multi-level determinants of late ART initiation (defined as CD4<100 cells/5L or WHO stage IV) among patients initiating ART. These methodologies include retrospective analysis of existing service-delivery data, in-depth clinic and program assessments, and a case-control study. In Aim 1, we will examine the influence of factors at multiple levels-contextual (e.g., urban/rural, testing coverage, stigma), clinic (e.g., appointment adherence support, active testing, staffing), and individual (e.g., age, sex, entry point). We will draw on an existing dataset of routinely-collected clinic-level and individual-level service-delivery data on 72,007 persons who initiated ART from 71 HIV care and treatment clinics in 23 sub-regions of nine African countries. These clinic and individual- level data will be combined with contextual-level data from nationally representative household surveys to examine the multi-level determinants of late ART initiation. Prior studies have not examined these multiple levels of influence over such a wide range of clinics and settings nor have they examined longitudinal data from the pre-ART phase of care leading up to ART initiation. Aims 2 and 3 we be carried at four clinics with historically low, medium, and high rates of late ART initiation. We will conduct in-depth clinic and program assessments to ascertain clinic-level enablers/barriers to earlier ART initiation (Aim 2). Lastly, as very little is known about individual-level risk factors for late ART initiation, we will conduct detailed interviews as part of a case-control study examining the role of normative and behavioral factors (e.g., health beliefs, depression, social-support, substance use) through interviews of 360 cases who started ART late and 360 controls who started ART earlier (Aim 3). The overarching goal of this study is to provide critical information to inform strategies for achieving more timely ART initiation, ultimately reducing HIV-related morbidity and mortality. PUBLIC HEALTH RELEVANCE: The US spends billions per year in tax payer dollars for the President's Emergency Plan for AIDS Relief (PEPFAR), much of which goes to the hardest hit region of sub-Saharan Africa. This project will improve our understanding about why HIV positive persons in sub-Saharan Africa start HIV treatment too late. This in turn will help identify ways to get people onto treatment earlier, thereby greatly improving their chances of survival, reducing the spread of HIV infection, and optimizing the cost-effectiveness of the PEPFAR program.