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

项目摘要/摘要 虽然最近艾滋病毒(PWH)患者的临床护理发生了重大变化(例如，普遍开展抗逆转录病毒治疗， 更多地使用他汀类药物作为预防措施)降低了心血管疾病(CVD)的风险 可能增加心血管疾病风险的发展(例如，转向整合酶抑制剂作为艾滋病毒的一线治疗， 艾滋病毒人口的持续老龄化)意味着威尔斯亲王医院心血管疾病的决定因素在不断变化。我们 有机会扩展我们现有的数据库-妇女与艾滋病毒相关的组学措施- 在MACS/WIHS联合队列研究(MWCCS)中将心血管疾病关联到男性，并扩大范围 微生物组、代谢组和性激素的附加评估。我们建议使用存档的 测定肠道微生物区系和选定的微生物组相关代谢物和免疫标志物的标本 包括免疫激活标志物、肠道屏障功能障碍和微生物易位之间的关系 对MWCCS男性颈动脉粥样硬化的影响，并评估性别的独立和中介作用 女性和男性艾滋病毒携带者之间的这种关系中的激素。我们的目标是支持艾滋病毒/艾滋病研究 属于以下NIH高度优先的艾滋病指定主题：1)免疫功能障碍，持续性 炎症，微生物组和基因决定因素，这些因素支撑着高度优先的艾滋病毒联合... 发病率，以及2)针对全球艾滋病毒相关并存疾病的长期治疗或预防战略 生命的长短。

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.