FOCUS ISSUE ON HIV AND THE CARDIOMETABOLIC SYNDROME

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 感染人类免疫缺陷病毒（HIV）、使用高效抗逆转录病毒药物治疗（HAART）、不良生活方式/行为选择、遗传背景和其他因素都导致相当数量的HIV感染成人和儿童出现不良代谢和形态学变化。 至少在发达国家，由于过去10年来在治疗方面取得的进展，艾滋病毒/艾滋病已从一定的死亡转变为一种慢性、可控制的疾病，有可能长期健康地生存。 但许多挑战仍然存在，正如本卷《代谢综合征杂志》中的文章所概述的那样。 随着生存时间的延长，艾滋病毒感染者是否会死于工业化国家老年人中最常见的死亡原因，特别是心脏代谢综合征的组成部分（心脏病、中风、肺病、糖尿病），但年龄更小？ HIV感染和伴随的慢性促炎过程是否会增加这些最常见死因的风险？心脏代谢综合征是否存在HIV特异性风险因素？最近的观察数据表明，在艾滋病毒感染者中，心血管疾病、糖尿病、非艾滋病毒相关癌症和药物滥用造成的死亡可能正在增加（4-8）。 此外，来自疾病预防控制中心的社会经济和人口数据表明，低收入，受教育程度低，难以获得医疗保健的年轻少数民族男性和女性在新感染艾滋病毒的人群中所占比例不成比例（2，3）。 这些人不正是普通人群中患糖尿病、肥胖症、心脏病和癌症的风险更高的群体吗？ 同样，艾滋病毒流行病在世界上资源有限的地区最为严重。 随着这些地区变得更加发达和工业化，我们预计会出现“流行病的碰撞”;艾滋病毒和心脏代谢综合征，最近的分析支持这一观点（1）。 这些问题很复杂，需要多学科团队和方法来解决。 更基本的问题留给生物医学科学家解决（即，本书的撰稿人及其同行），并包括：我们是在危言耸听吗？毕竟，我们只有10年的抗逆转录病毒药物经验。也许更新的药物和治疗模式会有更少的毒性。HIV、HAART、生活习惯和遗传易感性与心血管代谢综合征的发生之间的潜在机制是什么？ 这些机制是否为我们提供了针对HIV心脏代谢综合征的既定或新的治疗干预措施？通过研究HIV患者的心血管代谢综合征，我们能更多地了解普通人群中心血管代谢综合征的发病机制吗？免疫系统和心血管系统之间是否存在我们忽视的相互作用？技术和分析的进步（例如，成像，“组学”，RNA敲除）帮助我们识别，表征，或治疗艾滋病毒中不断发展的心脏代谢综合征？ 我们如何在世界各地开发、测试和实施更好的艾滋病毒心脏代谢综合征筛查、监测和治疗？在发达国家获得的关于艾滋病毒和高效抗逆转录病毒疗法的研究和知识是否适当地告知提供者如何在世界资源有限的地区治疗和管理艾滋病毒感染者？ 这些都是难题。他们强烈建议，必须继续支持对艾滋病毒和心脏代谢综合征的研究。我们认为，研究工作只触及了“冰山一角”。鉴于我们有限的HAART经验和HIV复制的复杂性，结合我们对血脂异常、炎症、内脏肥胖、胰岛素抵抗、不良饮食行为和身体不活动的致动脉粥样硬化倾向的广泛了解，我们只能想象这是未来HIV感染者中心脏代谢综合征流行病的“冰山一角”。我们希望科学家和临床医生继续寻求关于这些问题的公正知识和真相，并希望授权机构和政策制定者对这些知识做出适当的回应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Infection with human immunodeficiency virus (HIV), use of highly active antiretroviral drug therapies (HAART), undesirable lifestyle/behavioral choices, genetic background, and other factors all contribute to adverse metabolic and morphometric changes in appreciable numbers of adults and children living with HIV. At least in the developed world, HIV/AIDS has transitioned from certain death to a chronic, manageable condition with the potential for long-term salubrious survival, due to therapeutic advances made over the past 10yrs. But many challenges remain, as outlined by the articles in this volume of the Journal of the CardioMetabolic Syndrome. With longer-term survival, will HIV-infected people succumb to the causes of death that are most common among aging humans in the industrialized world, especially components of the cardiometabolic syndrome (heart disease, stroke, lung disease, diabetes), but at an earlier age? Does HIV-infection and the accompanying chronic proinflammatory processes, impart increased risk for these most common causes of death? Are there HIV-specific risk factors for the cardiometabolic syndrome? Recent observational data indicate that deaths from cardiovascular disease, diabetes, non-HIV-related cancer, and drug abuse may be increasing among HIV-infected people (4-8). In addition, socioeconomic and demographic data from the CDC suggest that low-income, poorly educated, young minority men and women with poor access to health care constitute a disproportionate percentage of people newly infected with HIV (2, 3). Are these not the same groups in the general population that are at greater risk for developing diabetes, obesity, heart disease, and cancer? Likewise, the HIV epidemic is most serious in resource-limited areas of the world. As these regions become more developed and industrialized, we anticipate a "collision of epidemics"; HIV and the cardiometabolic syndrome, and recent analyses support this notion (1). The issues are complex and will require multidisciplinary teams and approaches to resolve. The more fundamental questions are left to be resolved by the biomedical scientists (i.e., the contributing authors to this volume and their peers) and include: Are we being alarmist? After all, we only have 10yrs of experience with antiretroviral medications. Maybe newer medications and treatment paradigms will have fewer toxicities. What are the underlying mechanisms that link HIV, HAART, lifestyle habits, and genetic predisposition to the development of cardiometabolic syndromes? Do these mechanisms point us to established or novel therapeutic interventions for the cardiometabolic syndrome in HIV? By studying cardiometabolic syndrome in HIV, can we learn more about the pathogenesis of cardiometabolic syndrome in the general population? Are there interactions between the immune and cardiovascular systems that we are overlooking? Can technological and analytical advances (e.g., imaging, "omics", RNA knockdown) help us identify, characterize, or treat the evolving cardiometabolic syndrome in HIV? How can we develop, test, and implement better screening, monitoring, and treatments for the cardiometabolic syndrome in HIV in all parts of the world? Does the research and knowledge gained about HIV and HAART in the developed countries, properly inform providers about how to treat and manage HIV-infected people in resource limited regions of the world? These are all difficult questions. They strongly suggest that research on HIV and the cardiometabolic syndrome must continue to receive support. We propose that research efforts have only scraped the "tip of the iceberg". Given our limited experience with HAART and the complexities of HIV-replication, combined with our extensive knowledge of the proatherogenic disposition of dyslipidemia, inflammation, visceral adiposity, insulin resistance, poor eating behaviors and physical inactivity, one can only envision that this is the "tip of the iceberg" for a future epidemic of cardiometabolic syndrome in people living with HIV. We hope that scientists and clinicians continue to seek unbiased knowledge and the truth about these issues, and that granting agencies and policymakers respond to this knowledge appropriately.