Multicenter AIDS Cohort Study - Part B (Baltimore Center)

描述（由申请人提供）：此申请是为了更新研究以帮助艾滋病研究工作（SHARE），这是多中心艾滋病队列研究（MACS）的巴尔的摩-华盛顿特区站点。MACS于1983年由NIAID和NCI资助，在巴尔的摩-华盛顿、芝加哥、匹兹堡和洛杉矶设立了站点，研究男男性行为者感染艾滋病毒的自然历史。随着有效的抗逆转录病毒联合疗法（cART）的出现，MACS也成为对HIV感染治疗史的研究，包括长期控制的HIV感染与衰老相关的慢性疾病之间的关系。MACS参与者，包括1808名SHARE参与者，自1984年以来每半年随访一次，并提供问卷调查数据、体检数据、实验室数据（包括HIV血清状态、T细胞亚群测量和HIV病毒载量测量），以及大量血浆、血清、冷冻保存的外周血单个核细胞和其他标本。评估和跟踪SHARE和MACS中HIV感染的流行和事件病例，为HIV感染的危险因素，HIV感染建立后的监测和进展机制，宿主对HIV的防御，影响HIV发病机制的遗传因素，以及不同类型HIV和相关疾病治疗的使用，疗效和不良反应提供了关键见解。SHARE和MACS目前正在招募新的参与者，他们正在接受较新的cART方案，这些方案比旧方案更有效、更安全、更方便，并且在艾滋病毒感染过程的早期开始；本次招聘将于2014年3月本轮融资期结束前完成。SHARE 2014-9年更新期的具体目标反映了MACs的目标，并确定：不断发展的、早期启动的抗逆转录病毒治疗方案对hiv诱导的炎症和免疫功能障碍的影响；根据艾滋病毒感染和新的抗逆转录病毒治疗方案，新出现的、非艾滋病定义的、高发病率结果的发生和危险因素；恶性肿瘤的发病率、进展和生存的决定因素，包括艾滋病和非艾滋病定义；HIV感染治疗后对衰老过程的生物学和生理学影响；艾滋病毒感染中药物使用和衰老的社会心理因素与依从性、应对技能、恢复力、抑郁和生活质量以及与抵抗和控制艾滋病毒感染相关的遗传因素的关系。SHARE将通过领导八个专注于这些主题的MACS工作组，以及通过专注于肝脏疾病、能量代谢、巨细胞病毒感染和免疫激活和炎症调节的本地研究，为实现这些目标做出贡献。这些目标只有通过对这一极具特征的队列进行持续随访才能实现。SHARE和MACS应继续在促进更好地治疗和预防艾滋病毒感染的研究中发挥主导作用。

DESCRIPTION (provided by applicant): This application is for the renewal of the Study to Help the AIDS Research Effort (SHARE), which is the Baltimore-Washington DC site of the Multicenter AIDS Cohort Study (MACS). The MACS was funded by NIAID and NCI in 1983, with sites in Baltimore-Washington, Chicago, Pittsburgh, and Los Angeles to study the natural history of HIV infection in men who have sex with men. With the advent of effective combination antiretroviral therapy (cART), the MACS became also a study of the treated history of HIV infection, including the relationship between long-term controlled HIV infection and chronic diseases associated with aging. MACS participants, including 1808 enrolled in SHARE, have been followed semiannually since 1984 and have provided questionnaire data, physical exam data, laboratory data (including HIV serostatus, T cell subset measurements, and HIV viral load measurements), and a large repository of plasma, serum, cryopreserved peripheral blood mononuclear cells, and other specimens. Evaluating and following the prevalent and incident cases of HIV infection in SHARE and the MACS has provided key insights into risk factors for infection with HIV, monitoring and mechanisms of progression of HIV infection once it is established, host defense against HIV, genetic factors affecting HIV pathogenesis, and use, efficacy, and adverse effects of different types of therapy for HIV and related illnesses. SHARE and MACS are currently recruiting new participants who are receiving more recent cART regimens that are more potent, safer, and more convenient than older regimens, and which are initiated earlier in the course of HIV infection; this recruitment will be completed by the end of the current funding period in March, 2014. The specific aims of SHARE for the 2014-9 renewal period reflect those of the MACs and are to determine: the effect of evolving, earlier initiated c ART regimens on HIV-induced inflammation and immune dysfunction; the occurrence of and risk factors for emerging, non-AIDS-defining, high morbidity outcomes according to HIV infection and new c ART regimens; the determinants for incidence, progression and survival of malignancies, both AIDS- and non-AIDS-defining; the biologic and physiologic effects of treated HIV infection on the aging process; the relationships of substance use and psychosocial factors of aging in HIV infection with adherence, coping skills, resiliency, depression and quality of life and genetic factors associated with resistance to and control of HIV infection. SHARE will contribute to these goals through leadership of eight MACS working groups focusing on these topics, and through local studies focusing on liver disease, energy metabolism, cytomegalovirus infection, and regulation of immune activation and inflammation. These aims can be achieved only through continued follow-up of this extremely well-characterized cohort. SHARE and the MACS should continue to play a leading role in studies that will foster better treatments and prevention of HIV infection.