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

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 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.