Rates and determinants of decreased bone health among HIV-infected patients

HIV和HCV感染与骨质疏松性骨折（OF）的风险增加有关。HIV/HCV共- 与未感染者相比，感染者的骨折发生率增加了3倍， 比HIV单一感染者的风险更大。尽管与骨折风险高得多有关，但HIV/HCV共 与单独HIV感染相比，感染与较低的骨矿物质密度（BMD）无关。风险增加 与丙型肝炎病毒相关的是可能介导的微结构的变化，可以使用一种新的评估， 技术称为骨小梁评分（TBS）和可能更快的BMD下降。我们已经确认 在我们的初步研究中，这些HCV相关的微结构变化的存在，现在想 以探索它们是否是骨折风险增加的基础。利用我们正在进行的540名参与者（57 HIV/HCV感染者174例，HCV感染者131例，未感染者178例），我们将评估BMD和TBS HIV的纵向变化 HCV患者。 在HIV和HCV人群中，BMD和BMD变化对骨折风险的验证尚未进行。由于 除了对BMD的有害作用外，富马酸替诺福韦酯（TDF）现在在HIV中大部分被取代， 类似物替诺福韦艾拉酚胺（TAF）治疗。这一转变的有益效果也没有得到 在一个大的队列中进行评估。也没有骨折预防措施的坚持和有效性， HIV和HCV。分析这些预防措施和抗逆转录病毒治疗的使用和效果 变化将是我们研究的第二个目的。为了实现这一目标，我们将利用我们的前瞻性队列和 更大规模的回顾性队列患者接受治疗的VA网络，使用一种新的自然 语言处理工具，用于提取抗骨质疏松症药物处方，BMD和骨折数据， 记录 最后，HCV相关性骨折风险是否因干扰素治疗HCV而改善尚不确定， 最近的证据目前使用直接作用抗病毒药物（DAA）的HCV治疗对OF风险的影响尚未得到证实。 这是我们工作的第三个目标。我们的发现将对 对退伍军人的意义：1）了解与HCV相关的骨折风险增加的机制 将允许有针对性的预防和治疗干预; 2）分析BMD和TBS的纵向变化 将进一步阐明骨折风险增加的机制，并告知目前是否 监测指南是足够的; 3）确定HCV治疗与DAA是否改善HCV相关 增加的骨折风险将告知是否应采取额外措施来减轻骨折风险; 4）确定 在试验中观察到的抗逆转录病毒转换对BMD的有益作用是否将在改善的 一个大型临床队列的骨折风险将验证抗逆转录病毒治疗的当前趋势; 5）评估 一个大型HIV和非HIV队列中BMD与骨折风险的相关性以及 断裂预防措施将为今后的政策决定提供信息。

HIV and HCV infections are associated with an increased risk of osteoporotic fractures (OF). HIV/HCV co- infected subjects have a 3-fold increased fracture incidence compared to uninfected individuals, and 50% greater risk than HIV mono-infected. Despite being associated with this much higher fracture risk, HIV/HCV co- infection is not associated with lower bone mineral density (BMD) than HIV alone. The increased OF risk associated with HCV is likely mediated by micro-architectural changes that can be assessed using a novel technology called trabecular bone score (TBS) and possibly faster BMD decline. We have confirmed the existence of these HCV-associated micro-architectural changes in our preliminary studies and would now like to explore whether they underlie the increased fracture risk. Utilizing our ongoing cohort of 540 participants (57 HIV/HCV, 174 HIV, 131 HCV and 178 uninfected) we will evaluate longitudinal changes of BMD and TBS HIV and HCV patients. Validation of BMD and BMD changes on fracture risk in HIV and HCV populations has not been carried. Due to its deleterious effects on BMD, tenofovir disoproxil fumarate (TDF) is now largely being replaced in HIV therapy by the analog tenofovir alafenamide (TAF). The beneficial effects of this switch have also not been evaluated in a large cohort. Neither have the adherence and effectiveness of fracture preventive measures in HIV and HCV. Analyzing the use and effectiveness of these preventive measures and antiretroviral therapy changes will be the second aim of our study. To achieve this aim, we will utilize our prospective cohort and the much larger retrospective cohort of patients receiving care across the VA network, using a novel Natural Language Processing tool to extract anti-osteoporosis medication prescriptions, BMD and fracture data from the records. Finally, whether HCV-associated fracture risk is improved with HCV cure with interferon is doubtful based on recent evidence. The effects of current HCV therapy with Direct-Acting Antivirals (DAA) on OF risk has not been evaluated, and will constitute the third aim of our work. Our findings will have immediate therapeutic implications for Veterans: 1) understanding the mechanism(s) of increased fracture risk associated with HCV will allow targeted preventive and therapeutic interventions; 2) analyzing longitudinal changes in BMD and TBS in HIV and HCV will further elucidate mechanisms of increased fracture risk, and inform whether current monitoring guidelines are adequate; 3) determining whether HCV therapy with DAAs improves HCV-related increased fracture risk will inform whether additional measures should be taken to mitigate it; 4) determining whether the beneficial effect of antiretroviral switches on BMD seen in trials will be confirmed in improved fracture risk in a large clinical cohort will validate current trends in antiretroviral therapy; 5) evaluating the association of BMD and fracture risk in a large cohort of HIV and non-HIV and the use and effectiveness of fracture preventive measures will inform future policy decisions.