Point-of-care C-reactive protein-based tuberculosis screening in people living with HIV: a randomized trial

HIV 感染者基于 C 反应蛋白的即时结核病筛查：一项随机试验

基本信息

批准号：
10026339
负责人：
David Wesley Dowdy
金额：
$ 96.04万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10026339
关键词：
AIDS/HIV problem Acute-Phase Proteins Africa Africa South of the Sahara Area Biological Assay Blood capillaries Blood specimen C-reactive protein CD4 Lymphocyte Count Cells Characteristics Clinic Clinical Clinical Trials Data Detection Diagnosis Drug resistance in tuberculosis Economics Epidemic Epidemiology Fingers Future Generations Grant HIV HIV Seropositivity HIV diagnosis HIV/TB Incidence Individual Infection Interleukin-6 Intervention Lead Life Measures Mediating Microbiology Modeling Outcome Participant Patient-Focused Outcomes Peripheral Policies Population Preventive therapy Public Health Randomized Recommendation Regimen Research Resources Risk Savings Specificity Symptoms Testing Tuberculosis Uganda United States National Institutes of Health Work World Health Organization antiretroviral therapy base comparative cost effectiveness cost cost effective cost effective intervention cost effectiveness effectiveness evaluation improved improved outcome incremental cost-effectiveness innovation mortality point of care prevent primary endpoint primary outcome randomized trial routine practice scale up screening screening guidelines secondary outcome therapy outcome tool transmission process uptake

项目摘要

PROJECT SUMMARY Tuberculosis preventive therapy (TBPT) is among the most efficacious and cost-effective interventions to reduce tuberculosis (TB) incidence and mortality among people living with HIV (PLHIV) but is grossly underutilized due to our reliance on a symptom-based screening test to rule-out active TB. Studies from Africa have shown that symptom screening has low specificity (10-30%) for active TB and does not meet the minimum specificity (≥70%) requirement established by the World Health Organization (WHO) for TB screening. The low specificity is a major barrier to TBPT scale-up because if current TB screening guidelines were followed, 70-90% of PLHIV without active TB would not only be denied immediate initiation of TBPT but would also require unnecessary and costly confirmatory TB testing. The overall objective of this application is to evaluate the impact of a potentially more effective and cost-effective TB screening strategy, which is the next step required for successful uptake of TBPT. Our central hypothesis is that compared to symptom screening, a TB screening strategy based on C-reactive protein (CRP) levels, measured using a point-of-care (POC) assay, will improve TBPT uptake, thereby reducing TB incidence and its associated mortality among PLHIV. The scientific premise for this hypothesis is based on our own work that identified POC CRP as the first tool to meet the minimum sensitivity (≥90%) and specificity (≥70%) targets established by the WHO for TB screening. To accelerate scale-up of this promising TB screening strategy, and thus scale-up of TBPT, we propose a single-center individual randomized trial to evaluate the impact of POC CRP-based TB screening in 1720 PLHIV initiating antiretroviral therapy from 3 prototypical HIV clinics in Uganda. Participants will be randomized to either POC CRP- or symptom-based TB screening and followed for 2-years. Aim 1 will determine whether POC CRP-based TB screening improves 2-year clinical outcomes. The primary outcome for Aim 1 will be a composite of TB incidence and all-cause mortality. Key secondary outcomes include TB- specific mortality and incidence of drug-resistant TB. Aim 2 will determine the impact of POC CRP-based TB screening on intermediate outcomes related to the primary trial outcome. Primary outcomes for Aim 2 include the proportion of PLHIV (a) initiating TBPT and (b) diagnosed with prevalent TB. Secondary outcomes include the proportion of PLHIV (a) completing TBPT and (b) completing treatment for prevalent TB. Aim 3 will compare the cost-effectiveness and projected epidemiologic impact of TB screening with and without POC CRP. CRP testing will be performed using a low-cost ($2 per test), rapid (3 minutes) and simple (measured from capillary blood) POC assay, increasing the likelihood that POC CRP-based TB screening will be implemented in even the most peripheral settings. This research is significant because in addition to quantifying the expected clinic, economic, and epidemiologic benefits of TB screening, this work may enable the field to move beyond ineffective TB screening as a barrier to TBPT and improved outcomes of PLHIV.

项目概要结核病预防治疗（TBPT）是最有效和最具成本效益的干预措施之一降低艾滋病毒感染者 (PLHIV) 的结核病 (TB) 发病率和死亡率，但严重程度由于我们依赖基于症状的筛查测试来排除活动性结核病，因此未得到充分利用。非洲已经表明，症状筛查对于活动性结核病的特异性较低（10-30%），并且不符合世界卫生组织 (WHO) 针对结核病制定的最低特异性 (≥70%) 要求筛查特异性低是 TBPT 扩大规模的主要障碍，因为如果当前的结核病筛查指南存在问题。随访发现，70-90% 的无活动性 TB 的 PLHIV 不仅无法立即开始 TBPT，而且还需要不必要且昂贵的确认性结核病检测该应用的总体目标是评估潜在更有效和更具成本效益的结核病筛查策略的影响，该策略是成功吸收 TBPT 所需的下一步是与症状相比。筛查，一种基于 C 反应蛋白 (CRP) 水平的结核病筛查策略，使用现场护理进行测量 (POC) 检测将提高 TBPT 的吸收，从而降低结核病发病率及其相关死亡率该假设的科学前提是基于我们自己的工作，该工作将 POC CRP 确定为第一个。满足世界卫生组织针对结核病制定的最低敏感性（≥90%）和特异性（≥70%）目标的工具为了加速扩大这一有前景的结核病筛查策略，从而扩大 TBPT，我们一项单中心个体随机试验，旨在提出基于 POC CRP 的结核病筛查的影响乌干达 3 个典型艾滋病毒诊所的 1720 名艾滋病毒感染者将接受抗逆转录病毒治疗。随机接受 POC CRP 或基于症状的结核病筛查，并随访 2 年目标 1。确定基于 POC CRP 的结核病筛查是否可以改善 2 年临床结果。目标 1 将是结核病发病率和全因死亡率的综合结果，其中包括结核病-。目标 2 将确定基于 CRP 的 POC 结核病的具体死亡率和发病率。与主要试验结果相关的中间结果的筛选包括目标 2 的主要结果。 (a) 开始 TBPT 和 (b) 诊断为流行性结核病的艾滋病毒感染者的比例包括次要结果。 (a) 完成 TBPT 和 (b) 完成流行结核病治疗的艾滋病毒感染者比例比较有和没有 POC 的结核病筛查的成本效益和预计的流行病学影响 CRP 测试将采用低成本（每次测试 2 美元）、快速（3 分钟）和简单（测量）的方式进行。毛细血管血）POC 检测，增加了基于 CRP 的 POC 结核病筛查的可能性即使在最外围的环境中实施这项研究也很重要，因为除了量化结核病筛查的预期临床、经济和流行病学效益，这项工作可能使该领域超越了无效的结核病筛查作为 TBPT 的障碍，并改善了 PLHIV 的结果。