Chicago WIHS Consortium V (CWC)

描述(由申请人提供)：随着艾滋病毒预防治疗网络052的研究证明，早期抗逆转录病毒(ART)治疗可以降低艾滋病毒的性传播和临床事件的发生率，而且妇女占全球艾滋病毒携带者的50%，需要更好地了解艾滋病毒感染妇女如何开始、坚持和应对ART，以及这种疗法如何影响艾滋病毒/艾滋病的预防、治疗和护理/治愈。非裔美国妇女继续承担着妇女中艾滋病毒疾病的最大负担，新的艾滋病毒感染率、艾滋病诊断率和死亡率都高得不成比例。这项建议的主要目标是继续保持芝加哥WIHS联合会(CWC)作为临床研究地点和作为一个科学领袖财团的高水平生产力，该财团在推动我们对美国妇女艾滋病毒流行演变的了解方面有着良好的记录。我们将继续迅速招募和保留艾滋病毒携带者和高危妇女的代表性队列，收集最高质量的数据，以领导和进行创新的流行病学分析，并进行多学科调查，以确定已治疗的妇女艾滋病毒疾病的特征。在WIHS-V的五年期间，我们将继续设计、实施、综合和传播调查结果，这些调查探索艾滋病毒、抗逆转录病毒治疗、病毒抑制、社会人口学、行为、精神疾病、免疫生物标记物、更年期和共病之间的动态和复杂关系，而不是专注于任何单一因素的影响。CWC调查团队建议扩大和保留芝加哥队列，并对纵向社会/行为、临床、神经认知和发病机制数据应用分析建模，以开发和测试特定性别的预后指数(“WIHS指数”)。我们的目标是确定HIV疾病表型的心理、神经内分泌、遗传和免疫学预测因子，包括那些以炎症、激活和细胞衰老为特征的表型，并确定与HIV相关非艾滋病(HANA)共病的临床和临床前措施的相关性。由于证据表明，潜在的可改变因素，如未治疗的精神疾病，慢性生活压力，以及成瘾物质的使用，可以促进炎症和加速端粒缩短，端粒缩短是细胞衰老的关键分子标记物，我们将探索精神病学诊断、激素模式以及先天性和获得性免疫系统标记物之间的相互作用。考虑到这些可修改因素在我们的队列中的高比率，我们建议进行一项多点随机对照试验，以测试基于证据的计算机化定制干预，该干预基于跨理论模型，以同时处理旨在戒烟、提高ART依从性和有效管理压力、抑郁和体重的危险行为。通过WIHS V的这些努力，我们希望确定可用于所有级别的艾滋病毒护理(社区、诊所和实验室)的新工具，使临床医生和他们的女性患者能够改善艾滋病毒感染妇女的预后和生活。

DESCRIPTION (provided by applicant): With the HIV Prevention Treatment Network 052 study proving that early antiretroviral (ART) initiation reduces rates of HIV sexual transmission and clinical events, and with women making up 50% of people living with HIV globally, a better understanding of how women with HIV start, stay on and respond to ART and how this therapy impacts prevention, treatment, and care/cure of HIV/AIDS is needed. African American women continue to bear the largest burden of HIV disease among women, with disproportionately higher rates of new HIV infections, AIDS diagnoses, and mortality. The major goal of this proposal is to continue the high level of productivity of the Chicago WIHS Consortium (CWC) as both a clinical research site and as a consortium of scientific leaders with a track record of advancing our understanding of the evolving HIV epidemic in US women. We will continue to rapidly recruit and retain a representative cohort of women with and at risk for HIV, to collect th highest quality data in order to lead and pursue innovative epidemiologic analyses, and multidisciplinary investigations to characterize treated HIV disease in women. Over the WIHS-V five year period, we will continue to design, implement, synthesize, and disseminate findings from investigations which explore the dynamic and complex relationships between HIV, ART, viral suppression, sociodemographics, behaviors, mental illness, immune biomarkers, menopausal stage, and comorbidities rather than focusing on the impact of any one single factor. The CWC investigative team proposes to expand and retain the Chicago cohort and to apply analytic modeling to longitudinal social/behavioral, clinical, neurocognitive, and pathogenesis data to develop and test a gender specific prognostic index ("WIHS Index"). We aim to identify psychological, neuroendocrine, genetic, and immunologic predictors of HIV disease phenotypes, including those characterized by inflammation, activation, and cellular senescence and determine the association with clinical and pre-clinical measures of HIV associated non AIDS (HANA) co-morbidities. Since evidence suggests that potentially modifiable factors, such as untreated mental illness, chronic life stress, and use of addictive substances can contribute to inflammation and accelerate telomere shortening, a key molecular marker of cellular senescence, we will explore the interactions between psychiatric diagnoses, hormonal patterns, and markers of the innate and adaptive immune system. Given the high rates of these modifiable factors in our cohort, we propose a multi-site randomized controlled trial to test an evidence based computerized tailored intervention based on the Transtheoretical Model to address risk behaviors concurrently aimed at smoking cessation, improving ART adherence, and effectively managing stress, depression, and weight. Through these WIHS V efforts, we hope to identify new tools that can be used at all levels of HIV care (community, clinic, and laboratory) to empower clinicians and their female patients to improve the prognosis and lives of women with HIV.