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

HIV 感染者骨骼健康状况下降的比率和决定因素

• 批准号: 10049959
• 负责人: Roger Bedimo
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10049959
• 关键词: Accounting; Adherence; Aging; Anti-Retroviral Agents; Antiviral Agents; Antiviral Therapy; Architecture; Bone Density; Caring; Chronic; Clinical; Cohort Analysis; Computing Methodologies; Data; Databases; Defect; Diabetes Mellitus; Drug Prescriptions; Dual-Energy X-Ray Absorptiometry; Effectiveness; Enrollment; Fracture; Fumarates; Future; Goals; Guidelines; HIV; HIV Infections; HIV therapy; HIV/HCV; Health; Hepatitis C; Hepatitis C Therapy; Hepatitis C co-infection; Hepatitis C virus; Image; Incidence; Individual; Infection; Interferons; Lead; Longitudinal cohort; Measures; Mediating; Monitor; Natural Language Processing; Osteoporosis; Outcome; Participant; Patients; Pharmaceutical Preparations; Policies; Population; Predictive Value; Prevention; Prevention Measures; Preventive measure; Prospective cohort; Records; Regimen; Retrospective cohort; Risk; Safety; Scanning; Steroids; Techniques; Tenofovir; Therapeutic; Therapeutic Intervention; Trabecular Bone Score; Use Effectiveness; Validation; Veterans; Work; analog; antiretroviral therapy; base; bisphosphonate; bone; bone health; bone quality; bone turnover; co-infection; cohort; demineralization; epidemiologic data; follow-up; fracture risk; improved; interferon therapy; longitudinal analysis; new technology; novel; osteoporosis with pathological fracture; predictive marker; preventive intervention; response; risk prediction; skeletal; standard of care; tool; trend

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.

艾滋病毒和丙型肝炎病毒感染与骨质疏松性骨折的风险增加有关。艾滋病毒/丙型肝炎病毒联合 被感染者的骨折发生率是未感染者的3倍，50%。 比单一感染艾滋病毒的风险更大。尽管与这种高得多的骨折风险有关，艾滋病毒/丙型肝炎病毒共同 感染与骨密度(BMD)低于单独的HIV无关。风险的增加 与丙型肝炎病毒相关的基因很可能是由微体系结构变化介导的，这些微体系结构变化可以用一种新的 被称为骨小梁评分(TBS)的技术以及可能更快的BMD下降。我们已经确认了 在我们的初步研究中存在这些与丙型肝炎病毒相关的微结构变化，现在希望 以探讨它们是否导致骨折风险增加。利用我们正在进行的540名参与者(57名 HIV/丙型肝炎病毒174例，丙型肝炎131例，未感染178例)我们将评估骨密度和TBS HIV的纵向变化 和丙型肝炎患者。 骨密度和骨密度变化对HIV和丙型肝炎病毒人群骨折风险的验证尚未进行。到期 由于其对骨密度的有害影响，富马酸替诺福韦(TDF)现在正在很大程度上被HIV替代 用类似物替诺福韦丙氨酰胺(TAF)治疗。这一转变的有益影响也没有 在一大群人中进行评估。骨折预防措施的坚持性和有效性也不高 艾滋病毒和丙型肝炎病毒。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标。为了实现这一目标，我们将利用我们的预期队列和 通过退伍军人管理局网络接受护理的患者的回溯性队列要大得多，使用一种新的Natural 用于提取抗骨质疏松药物处方、BMD和骨折数据的语言处理工具 这些记录。 最后，丙型肝炎病毒与干扰素联合治疗是否能改善与丙型肝炎病毒相关的骨折风险是值得怀疑的。 最近的证据。目前使用直接作用抗病毒药物(DAA)治疗丙型肝炎病毒对风险的影响尚未见报道 经过评估，并将构成我们工作的第三个目标。我们的发现将立即产生治疗作用 对退伍军人的启示：1)了解丙型肝炎相关骨折风险增加的机制(S) 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 监测指南是足够的；3)确定使用DAA治疗丙型肝炎是否改善了丙型肝炎病毒相关 骨折风险的增加将决定是否应该采取额外的措施来缓解它；4)确定 在试验中看到的抗逆转录病毒开关对骨密度的有益影响是否会在改进后得到证实 大型临床队列中的骨折风险将验证抗逆转录病毒治疗的当前趋势；5)评估 在一大群HIV和非HIV人群中，骨密度与骨折风险之间的关系，以及使用和有效性 骨折预防措施将为未来的政策决策提供参考。