Risk for Bone Loss Among Individuals with HIV in a Resource-Limited Environment

在资源有限的环境中艾滋病毒感染者的骨质流失风险

• 批准号: 9150343
• 负责人: Evelyn Hsieh
• 金额: $ 13.83万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-27 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150343
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adopted; Algorithms; Awareness; Bone Density; Bone Resorption; Caring; China; Chinese People; Chronic; Clinic; Data; Development; Diagnosis; Doctor of Philosophy; Early identification; Environment; Focus Groups; Fostering; Fracture; Future; Goals; Gold; HIV; Hand; Health; Health Care Costs; Hospitals; Individual; International; Intervention; Intervention Trial; Interview; Knowledge; Lamivudine; Lead; Life; Long-Term Care; Low Prevalence; Measurement; Measures; Mediating; Mentorship; Methods; Modeling; Musculoskeletal Diseases; Osteoporosis; Patients; Pattern; Pilot Projects; Population; Prevention; Prevention strategy; Provider; Regimen; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Rheumatism; Rheumatology; Risk; Risk Assessment; Risk Factors; Risk Reduction; Series; Site; Subgroup; Target Populations; Tenofovir; Time; Training; Viral; Vulnerable Populations; antiretroviral therapy; base; bone; bone loss; cohort; cost; cost effectiveness; design; disability; efavirenz; experience; formative assessment; global health; health training; high risk; improved; improved outcome; low and middle-income countries; medical schools; meetings; mortality; multidisciplinary; osteoporosis with pathological fracture; population based; quantitative ultrasound; training opportunity; uptake

 DESCRIPTION (provided by applicant): Patients with human immunodeficiency virus (HIV) are at increased risk for osteoporosis and fracture due to host, viral and in particular, antiretroviral therapy (ART)-mediated factors. In China, as in other low- and middle-income countries, access to ART for individuals with HIV has increased dramatically over the past decade, however infrastructure for the diagnosis and management of osteoporosis is still severely lacking. Certain ARTs, including tenofovir, exert an especially profound effect on bone. In 2012, tenofovir was made available as first-line ART for individuals with HIV in China. Our prior research suggests that tenofovir therapy leads to higher levels of bone resorption at two years among Chinese individuals with HIV compared with data from non-Chinese populations. However no studies have evaluated the impact of this robust and prolonged bone resorption on bone mineral density (BMD), nor addressed the challenges of developing fracture risk reduction strategies for this population that are targeted and pragmatic. Our current proposal seeks to bridge these gaps by exploring the application of quantitative ultrasound (QUS), a portable and low-cost method of assessing BMD that has been shown to reliably predict fracture. We will first establish a longitudinal cohort of Chinese individuals with HIV in Beijing, and follow them prospectively over two years to measure change in BMD after initiation of tenofovir-lamivudine-efavirenz therapy using dual- energy x-ray absorptiometry (DXA), the gold standard for BMD measurement. We will then use latent class analysis to identify subgroups of individuals at greatest risk for bone loss within the overall cohort, and the risk factors that predict categorization into each subgroup. All patients will have concurrent QUS measurements, allowing us to determine whether QUS is capable of identifying the same latent subgroups compared with DXA. Finally, we will perform a mixed-methods assessment of facilitators and barriers to implementation of potential fracture risk reduction strategies in a low-resource HIV-care setting in China, and evaluate feasibility and uptake of components that can be applied in future intervention trials. Our overarching goal is to provide an algorithm for identifying individuals at greatest need for fracture risk reduction, and targeted interventions that can be incorporated into the long-term care of patients with HIV in settings with limited resources. My longstanding commitment to global health research has prompted me to pursue global health training opportunities abroad to gain hands on experience in carrying out international collaborative research projects. As a Rheumatology fellow and PhD candidate, I assembled a strong multidisciplinary mentorship team at Yale and Peking Union Medical College Hospital in Beijing, China to strengthen my training. In the current proposal, these two sites will continue to serve as outstanding training grounds to foster my development into an independent investigator in global health with a focus on improving outcomes for musculoskeletal and rheumatic diseases among vulnerable populations in resource-limited environments.

 描述（由申请方提供）：由于宿主、病毒，特别是抗逆转录病毒治疗（ART）介导的因素，人类免疫缺陷病毒（HIV）患者骨质疏松症和骨折的风险增加。在中国，与其他低收入和中等收入国家一样，艾滋病毒感染者获得抗逆转录病毒治疗的机会在过去十年中大幅增加，但诊断和管理骨质疏松症的基础设施仍然严重缺乏。 某些ART，包括替诺福韦，对骨骼产生特别深远的影响。2012年，替诺福韦成为中国艾滋病毒感染者的一线抗逆转录病毒药物。我们之前的研究表明，与非中国人群的数据相比，替诺福韦治疗导致中国HIV感染者两年时骨吸收水平更高。然而，没有研究评估这种稳健和长期的骨吸收对骨矿物质密度（BMD）的影响，也没有解决为该人群制定有针对性和实用的骨折风险降低策略的挑战。 我们目前的建议旨在通过探索定量超声（QUS）的应用来弥合这些差距，定量超声是一种便携式和低成本的骨密度评估方法，已被证明可以可靠地预测骨折。我们将首先在北京建立一个中国HIV感染者的纵向队列，并前瞻性地随访他们超过两年，以使用双能X射线吸收测定法（DXA）（BMD测量的金标准）测量开始替诺福韦-拉米夫定-依法韦仑治疗后BMD的变化。然后，我们将使用潜在类别分析来确定整个队列中骨丢失风险最大的个体亚组，以及预测每个亚组分类的风险因素。所有患者将同时进行QUS测量，使我们能够确定与DXA相比，QUS是否能够识别相同的潜伏亚组。最后，我们将在中国低资源的艾滋病护理环境中对实施潜在骨折风险降低策略的促进因素和障碍进行混合方法评估，并评估可用于未来干预试验的组件的可行性和吸收。我们的总体目标是提供一种算法，用于识别最需要降低骨折风险的个体，以及可以在资源有限的情况下纳入艾滋病毒患者长期护理的有针对性的干预措施。 我对全球卫生研究的长期承诺促使我在国外寻求全球卫生培训机会，以获得开展国际合作研究项目的经验。作为一名流变学研究员和博士候选人，我在耶鲁大学和中国北京协和医院组建了一个强大的多学科导师团队，以加强我的培训。在目前的建议中，这两个地点将继续 作为优秀的培训基地，以促进我发展成为一个独立的调查员在全球健康，重点是改善成果的肌肉骨骼和风湿性疾病的弱势群体在资源有限的环境。