Center/Coordination, Analysis and Management/MACS

这项申请是为了更新多中心艾滋病队列研究(MACS)，这是一项全面的质量保证 对7000多名男性进行的前瞻性队列研究，发表了近1300篇关于 艾滋病毒感染的自然历史和有效的联合抗逆转录病毒疗法(CART)的影响。这个 继续动态登记的现有队列的后续行动将有助于阐明长期的 CART的效果，包括新的和不断发展的CART方案，在男男性行为者(MSM)中， 美国受艾滋病毒影响最大的人群。互委会的首要目标是继续 阐明感染的生物学以及治疗和未治疗的感染的临床结果，结合 免疫学、病毒学、遗传学和心理社会学方法。互委会的科学议程侧重于 四个主要领域：1)艾滋病毒相关和非艾滋病的临床流行病学--确定结果，特别是 强调CART和年龄的影响；2)艾滋病毒易感性、疾病的致病机制 进展和治疗反应，包括遗传和其他分子因素；3)心理社会因素， 包括影响艾滋病毒感染风险、共病和治疗利用的药物使用；以及4) 开发新的应用方法论。对未感染艾滋病毒的男男性行为者进行同样的标准化 协议将有助于区分艾滋病毒、年龄、遗传学、混合感染和行为对 非艾滋病定义结果的发展，包括恶性肿瘤和老龄化。悬而未决的角色 炎症和免疫激活，以及更快的免疫系统衰老，在疾病过程中 将对接受治疗的艾滋病毒进行调查。有关联样本的数据，特别是来自700多个艾滋病毒血清转换器的数据， 为研究艾滋病毒的整个自然历史提供了无与伦比的资源，从感染前到感染前 (例如，易受感染)，通过治疗到老年和死亡。Mac现在是，将来也会是 继续处于解决这些问题的理想地位，因为其长期标准化的后续行动，以及 自1984年以来每半年收集一次的超过100万份标本的广泛存储库，以及 适当的HIV-MSM控制组，以及一支经验丰富并不断扩大的有经验的调查干部队伍。

This application is to renew the Multicenter AIDS Cohort Study (MACS), a comprehensive quality-assured prospective cohort study of over 7000 men, which has contributed almost 1300 research papers on the natural history of HIV infection and the impact of effective combination antiretroviral therapies (cART). The follow-up of the existing cohort with continuing dynamic enrollment will enable elucidation of long-term effects of cART, including newer and evolving cART regimens, in men who have sex with men (MSM), the largest population impacted by HIV in the U.S. The overarching goals of the MACS are to continue to elucidate the biology of infection and the clinical outcomes of treated and untreated infection, combining immunologic, virologic, genetic and psychosocial approaches. The scientific agenda of the MACS focuses on four primary areas: 1) clinical epidemiology of HIV-related and non-AIDS-defining outcomes with particular emphasis on the effects of cART and age; 2) pathogenic mechanisms underlying HIV susceptibility, disease progression and treatment response including genetic and other molecular factors; 3) psychosocial factors, including substance use which influence risk of HIV infection, co-morbidities and treatment utilization; and 4) development of novel applied methodology. Following HIV-uninfected MSM with the same standardized protocols will facilitate distinguishing the contributions of HIV, age, genetics,co-infections and behaviors on the development of non-AIDS-defining outcomes including malignancies, and aging. The role of unresolved inflammation and immune activation, and more rapid senescence of the immune system, on disease course in treated HIV will be investigated. Data with linked specimens, particularly from over 700 HIV seroconverters, provides an unparalleled resource for studying the entire natural history of HIV, ranging from pre-infection (e.g. susceptibility) to infection, through treatment to old age and death. The MACS is and will continue to be ideally positioned to address these issues because of its long-term standardized follow-up, an extensive repository of over 1 million specimens that have been collected semiannually since 1984, an appropriate control group of HIV- MSM, and a seasoned and expanding cadre of experienced investigators.