Sex differences in the role of multi-omics in HIV-associated carotid artery atherosclerosis

项目总结/摘要 虽然最近在艾滋病毒感染者（PWH）的临床护理方面发生了重大变化（例如，普遍启动抗逆转录病毒疗法， 更多地使用他汀类药物作为预防）降低了心血管疾病（CVD）风险，同时 可能增加CVD风险的发展（例如，将整合酶抑制剂作为HIV一线治疗， 艾滋病病毒感染者人口持续老化）意味着影响威尔斯亲王医院心血管疾病的决定因素不断变化。我们 有机会扩展我们现有的数据库，在妇女中与艾滋病毒有关的组学措施， 在MACS/WIHS联合队列研究（MWCCS）中，将CVD相关性纳入男性，并扩大范围， 微生物组、代谢组和性激素的额外评估。我们建议使用存档 用于测量肠道微生物群和选定的微生物群相关代谢物和免疫标志物的样本 面板，包括免疫激活，肠道屏障功能障碍和微生物易位的标志物， MWCCS男性颈动脉粥样硬化，并评估性别的独立和中介作用 荷尔蒙在这种关系中的作用。我们的目标是支持艾滋病毒/艾滋病研究， 福尔斯属于以下NIH高优先级AIDS指定主题：1）免疫功能障碍，持续性 炎症，以及微生物组和遗传决定因素，这些决定因素是高优先级艾滋病毒共同发展的基础， 发病率，和2）艾滋病毒相关共病的长期治疗或预防策略， 寿命

PROJECT SUMMARY/ABSTRACT While significant recent changes in the clinical care of people with HIV (PWH) (e.g., universal ART initiation, greater use of statins as prophylaxis) have reduced cardiovascular disease (CVD) risk, concurrent developments that may increase CVD risk (e.g., shift to integrase inhibitors as first-line HIV treatment, continued aging of the HIV population) mean that the determinants of CVD in PWH are ever-changing. We have the opportunity to extend our existing database of -omics measures in women in relation to HIV- associated CVD in the MACS/WIHS Combined Cohort Study (MWCCS) to men, and expand the scope with additional assessments of the microbiome, metabolome, and sex hormones. We propose to use archived specimens to measure gut microbiota and selected microbiome-related metabolites and immune marker panels, including markers of immune activation, gut barrier dysfunction and microbial translocation in relation to carotid atherosclerosis in MWCCS men, and assess both the independent and mediating roles of sex hormones in this relationship among both women and men with HIV. Our aims support HIV/AIDS research that falls under the following NIH high priority AIDS-designated topics: 1) immune dysfunction, persistent inflammation, and microbiome and genetic determinants that underpin the development of high priority HIV co- morbidities, and 2) long-term treatment or prevention strategies for HIV-relevant comorbid conditions across the lifespan.