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

 描述(申请人提供)：由于宿主、病毒，特别是抗逆转录病毒疗法(ART)介导的因素，人类免疫缺陷病毒(HIV)患者患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，艾滋病毒携带者获得抗逆转录病毒治疗的机会在过去十年里大幅增加，但诊断和治疗骨质疏松症的基础设施仍然严重缺乏。某些疗法，包括替诺福韦，对骨骼产生特别深远的影响。2012年，替诺福韦作为一线药物在中国用于艾滋病毒携带者。我们先前的研究表明，与非中国人群的数据相比，泰诺福韦治疗在两年内导致中国HIV感染者的骨吸收水平更高。然而，还没有研究评估这种强健和持久的骨吸收对骨密度(BMD)的影响，也没有研究解决为这一人群开发具有针对性和实用性的骨折风险降低策略所面临的挑战。我们目前的建议试图通过探索定量超声(QUS)的应用来弥合这些差距，QUS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中国HIV感染者的纵向队列，并前瞻性跟踪他们两年多的时间，使用双能X射线吸收法(DXA)测量开始使用替诺福韦-拉米夫定-伊法韦仑治疗后的骨密度变化，双能X射线吸收法(DXA)是骨密度测量的金标准。然后，我们将使用潜在类别分析来确定总体队列中具有最大骨质丢失风险的个体的亚组，以及预测分类到每个亚组的风险因素。所有患者将同时进行QUS测量，使我们能够确定QUS是否能够识别与DXA相同的潜伏期亚群。最后，我们将对中国低资源艾滋病毒护理环境中实施潜在骨折风险降低策略的促进者和障碍进行混合方法评估，并评估可应用于未来干预试验的组件的可行性和采集性。我们的首要目标是提供一种算法，用于识别最需要减少骨折风险的个人，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。我对全球健康研究的长期承诺促使我在国外寻求全球健康培训机会，以获得开展国际合作研究项目的实践经验。作为风湿病研究员和博士生，我在耶鲁大学和北京协和医院组建了一支强大的多学科导师团队，中国，以加强我的培训。在目前的提案中，这两个地点将继续 作为杰出的培训基地，促进我发展成为全球卫生领域的独立调查员，重点是在资源有限的环境中改善脆弱人群中肌肉骨骼和风湿病的结果。

 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.