Epidemiology of atherosclerosis among older-age individuals with HIV in Uganda

描述：撒哈拉以南非洲有800多万艾滋病毒/艾滋病患者正在接受抗逆转录病毒疗法(ART)。随着艾滋病毒相关死亡率的下降，50岁以上艾滋病毒感染者的人口正在迅速增加，预计到2040年将达到1000万人。不断变化的流行病正在推动公共卫生范式的转变，使其更加注重改善长期健康。来自资源丰富的环境的数据描述了艾滋病毒感染者与未感染者相比动脉粥样硬化率的增加。风险升高的根本原因来自多因素过程，包括传统的心血管风险因素、免疫功能改变、抗逆转录病毒药物的毒性以及与艾滋病毒感染相关的炎症状态升高。然而，撒哈拉以南非洲地区很大程度上缺乏关于心血管危险因素和结果的类似数据，那里是全球70%艾滋病毒感染者的家园。我们将利用乌干达姆巴拉拉一家由PEPFAR支持的公共艾滋病毒诊所的高效和成熟的研究基础设施，让50岁以上的PLWHA参加抗逆转录病毒治疗，并从NIH资助的、基于人口的医院覆盖地区社交网络研究中抽取一个年龄和性别匹配的未感染艾滋病毒的对照组。我们的目标是在撒哈拉以南非洲的农村地区测量PLWHA和年龄和性别匹配的未感染艾滋病毒的对照组中动脉粥样硬化的患病率和相关性。我们感兴趣的结果将是：动脉粥样硬化的测量，包括：1)颈动脉内膜中层厚度，2)踝臂指数，3)心电图上Q波的存在。我们感兴趣的风险因素将是：传统的心血管疾病风险因素(年龄、性别、心血管疾病家族史、吸烟史、饮食、活动、体重指数、糖尿病的患病率、高血压的患病率)和HIV相关的心血管风险因素(最低CD4计数、ART持续时间、肠道和血浆微生物群组成，以及免疫激活和全身炎症的标记物)。我们在撒哈拉以南非洲的农村地区建立了完善的研究基础设施，并在艾滋病毒感染人群的心血管疾病流行病学研究方面处于世界领先地位。我们将利用这些优势来报告PLWHA中的动脉粥样硬化性疾病负担，以及对艾滋病毒相关风险因素的最先进的分子和免疫学测试。这项研究的结果将用于申请NIH R01申请，用于在撒哈拉以南非洲的PLWHA中进行关于抗逆转录病毒治疗的心血管疾病的纵向研究。我们的总体目标包括：1)确定撒哈拉以南非洲地区老年PLWHA的高负担健康状况；2)确定可改变的风险因素以进行预防和干预以改善心血管结果；以及3)为未来的研究设定优先事项。

DESCRIPTION: Over 8 million people living with HIV/AIDS (PLWHA) in sub-Saharan Africa are taking antiretroviral therapy (ART). As HIV-related mortality declines, the population of HIV-infected persons over 50 years is rapidly increasing, and is expected to reach 10 million persons by 2040. The changing epidemic is motivating a public health paradigm shift towards a greater focus on improving long-term health. Data from resource-rich settings describe increased rates of atherosclerosis in HIV-infected versus HIV-uninfected persons. Root causes of the elevated risk arise from a multi-factorial process involving traditional cardiovascular risk factors, altere immune function, toxicity of ART, and the elevated inflammatory state associated with HIV infection. However, similar data on cardiovascular risk factors and outcomes are largely lacking from sub-Saharan Africa, which is home to 70% of HIV-infected persons globally. We will leverage a highly productive and established research infrastructure at a PEPFAR-supported, public HIV clinic in Mbarara, Uganda to enroll PLWHA on ART over 50 years of age, and an age and gender-matched HIV-uninfected comparison group sampled from an NIH- funded, population-based study of social networks in the hospital catchment area. We aim to measure the prevalence and correlates of atherosclerosis among PLWHA and age and gender-matched HIV- uninfected controls in rural, sub-Saharan Africa. Our outcomes of interest will be: measures of atherosclerosis, including: 1) carotid intima-media thickness, 2) ankle-brachial index, and 3) presence of q-waves on electrocardiogram Our exposures of interest will be: traditional cardiovascular disease risk factors (age, gender, family history of cardiovascular disease, smoking history, diet, activity, body mass index, prevalence of diabetes, and prevalence of hypertension) and HIV-related cardiovascular risk factors (nadir CD4 count, ART duration, gut and plasma microbiome composition, and markers of both immune activation and systemic inflammation). We combine a well-established research infrastructure in a rural, sub-Saharan African setting with world leaders in the study of cardiovascular disease epidemiology in HIV-infected populations. We will leverage these strengths to report atherosclerotic disease burden among PLWHA, as well as state-of- the-art molecular and immunologic testing for HIV-related risk factors. Results from this study will be used to apply for an NIH R01 application for longitudinal study of cardiovascular disease among PLWHA on ART in sub-Saharan Africa. Our over-arching aims include: 1) determination of high-burden health conditions for aging PLWHA on ART in sub-Saharan Africa, 2) identification of modifiable risk factors for prevention and interventions to improve cardiovascular outcomes, and 3) setting priorities for future research.