Screening for atherosclerotic vascular disease in HIV-infected children

HIV感染儿童的动脉粥样硬化性血管疾病筛查

• 批准号: 8839837
• 负责人: RICHARD H HAUBRICH
• 金额: $ 34.45万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-25 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8839837
• 关键词: Adult; Affect; Africa; Age; Algorithms; Atherosclerosis; Biological Markers; Birth; Blood Pressure; Blood Vessels; CCL2 gene; Cardiovascular system; Caring; Child; Chronic; Clinic; Clinical; Controlled Study; Country; Development; Diagnosis; Diagnostic; Diastolic blood pressure; Diet; Dietary Intervention; Disease; Early Intervention; Elasticity; Ensure; Equipment; Event; Evolution; Exercise stress test; Family; Family member; Fasting; Fibrin fragment D; Gender; Glucose; Gold; HIV; Health; Heart Rate; Human immunodeficiency virus test; Immune; Individual; Inflammation; Inflammatory; Institutes; Intercellular adhesion molecule 1; Interleukin-1; Interleukin-6; Lipids; Longevity; Low income; Manuals; Measures; Medical; Methods; Modeling; Morbidity - disease rate; Myocardial Infarction; Nurses; Outcome; Pathogenesis; Pharmaceutical Preparations; Physiologic pulse; Population; Primary Health Care; Recovery; Recruitment Activity; Regimen; Reporting; Resources; Risk; Risk Factors; Sensitivity and Specificity; Siblings; Source; South Africa; Southern Africa; Specificity; Stratification; Stroke; TNF gene; Testing; Therapeutic Intervention; Tobacco smoke; Urine; Validation; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Viral; Visit; adiponectin; antiretroviral therapy; burden of illness; cohort; cost; disorder risk; experience; follow-up; high risk; lifestyle intervention; mortality; pediatric human immunodeficiency virus; public health relevance; resistin; screening; skills; socioeconomics; standard of care; therapy duration; tool; waist circumference

 DESCRIPTION (provided by applicant): In South Africa, HIV-infected children in poorer families are often responsible for the parental care of younger (often uninfected) siblings and so any disease events they experience have far-reaching consequences. As in adults, atherosclerosis due to HIV-related chronic inflammation despite adequate viral suppression is a growing concern for children on antiretroviral therapy (ART). Effective lifestyle, diet and therapeutic interventions are available but efficacy is limited unless instituted early in pathogenesis of atherosclerosis. Diagnosis of asymptomatic increased atherosclerosis risk requires effective nationwide surveillance at primary health clinic level. This longitudinal cohort control study intends to quantify excess atherosclerosis risk in HIV-infected children on ART and to generate and validate a low tech screening algorithm to identify affected asymptomatic individuals using simple input variables that can be routinely collected during primary healthcare follow-up. AIM 1 will investigate the magnitude and longitudinal evolution of atherosclerotic vascular disease (AVD) risk in virally-suppressed perinatally-infected children on ART. Aorto-femoral pulse wave velocity (PWV), a measure of arterial elasticity, predicts incident cardiovascular events in asymptomatic adults and is a reliable gold- standard marker of subclinical atherosclerosis. We will compare longitudinal change in PWV Z-score over 5 years in children with and without HIV. PWV in this Primary Cohort will be adjusted for systolic blood pressure, fasting lipids, glucose, BMI, diet and tobacco smoke exposure. AIM 2 will generate a low tech, low cost, scalable diagnostic screening algorithm to detect asymptomatic increased AVD risk (defined as abnormally raised PWV) in a resource limited setting. We will compare various candidate screening tests that are predictive of incident cardiovascular events in adults, with PWV as a gold standard. Measures collected in the Primary Cohort will be used to develop the algorithm. Measures will be repeated in a Validation Cohort of 75 additional pre-pubertal HIV-infected children receiving the national first- line ART regimen in a programmatic setting, who will be recruited in year 3 and followed longitudinally until year 5 to validate the sensitivit and specificity of the algorithm. AIM 3 will investigate whether the circulating biomarkers most strongly predictive of vascular disease in adults correlate with abnormal PWV in virally-suppressed children and are useful for identifying increased AVD risk. Expected outcomes: A simple surveillance tool will enable nurse-driven, low-cost, high-efficacy country-wide surveillance for increased AVD risk in HIV-infected children on ART using widely-available equipment and easily-obtainable skills, facilitating therapeutic intervention early in pathogenesis Ultimately, early intervention will substantially reduce overall AVD burden in adulthood in this high-risk population, preserving their ability to care for the needs of family members and younger siblings.

 描述（由申请人提供）：在南非，贫困家庭中感染艾滋病毒的儿童通常负责照顾年幼（通常未感染）的兄弟姐妹，因此他们经历的任何疾病事件都会产生深远的影响。与成人一样，尽管有足够的病毒抑制，但由于 HIV 相关的慢性炎症而导致的动脉粥样硬化是接受抗逆转录病毒治疗 (ART) 的儿童日益关注的问题。有效的生活方式、饮食和治疗干预措施是可行的，但除非在动脉粥样硬化发病的早期采取，否则疗效有限。无症状动脉粥样硬化风险增加的诊断需要在初级卫生诊所层面进行有效的全国性监测。这个纵向队列 对照研究旨在量化接受 ART 的 HIV 感染儿童的过度动脉粥样硬化风险，并生成和验证一种低技术筛查算法，以使用可在初级保健随访期间常规收集的简单输入变量来识别受影响的无症状个体。 AIM 1 将调查接受 ART 治疗且病毒抑制的围产期感染儿童动脉粥样硬化性血管疾病 (AVD) 风险的程度和纵向演变。主动脉股动脉脉搏波速度 (PWV) 是动脉弹性的一种测量方法，可预测无症状成人的心血管事件，是亚临床动脉粥样硬化的可靠金标准标志物。我们将比较感染和未感染 HIV 的儿童 PWV Z 评分在 5 年内的纵向变化。该主要队列中的 PWV 将根据收缩压、空腹血脂、血糖、BMI、饮食和烟草烟雾暴露进行调整。 AIM 2 将生成一种低技术、低成本、可扩展的诊断筛查算法，以在资源有限的环境中检测无症状增加的 AVD 风险（定义为 PWV 异常升高）。我们将比较各种可预测成人心血管事件的候选筛查测试，并以 PWV 作为黄金标准。在主要队列中收集的测量结果将用于开发算法。将在由 75 名青春期前 HIV 感染儿童组成的验证队列中重复这些措施，这些儿童在规划环境中接受国家一线 ART 治疗方案，这些儿童将在第 3 年招募，并纵向跟踪直至第 5 年，以验证算法的敏感性和特异性。 AIM 3 将调查最能强烈预测成人血管疾病的循环生物标志物是否与病毒抑制儿童的 PWV 异常相关，并有助于识别 AVD 风险增加。预期成果：一个简单的监测工具将能够利用广泛可用的设备和易于获得的技能，在全国范围内对接受 ART 的 HIV 感染儿童的 AVD 风险增加进行护士驱动、低成本、高效率的监测，促进发病早期的治疗干预最终，早期干预将大大减少这一高危人群成年后的总体 AVD 负担，保持他们照顾孩子的能力 家庭成员和弟弟妹妹的需求。