Lung Microbiome in Cohorts of HIV-Infected Persons (Lung MicroCHIP) Study

描述(申请人提供)：虽然研究微生物群落的技术已经可用，但它尚未全面应用于感染艾滋病毒的呼吸道。我们的中心假设是，肺的微生物群是由艾滋病毒感染、艾滋病毒介导的免疫抑制程度以及抗逆转录病毒和抗微生物治疗的使用而形成的。此外，我们假设肺部的微生物群在健康和肺炎期间会发生变化，肺内特定微生物或微生物吸收的存在与艾滋病毒相关肺部并发症和死亡率的发展有关。我们建议进行一系列横断面和纵向研究，以确定急性和早期HIV感染、慢性HIV感染和机会性肺炎患者肺部存在的细菌、病毒和真菌微生物群的特征。我们建议使用三个微阵列，16S rRNA植物芯片、病毒芯片和18S rRNA真菌芯片作为经济、标准化的工具，在大量HIV患者样本中提供高分辨率的微生物组图谱。为了补充微阵列分析并获得微生物群落行为和相关宿主反应的功能图谱，我们将对从这些样本的子集生成的cDNA进行下一代454焦磷酸测序。这些研究将在OPTIONS、SCOPE和IHOP队列中进行，这三个队列是以旧金山大学旧金山分校为基地的艾滋病毒感染患者和未感染艾滋病毒患者的既定和特征良好的队列。我们提出的具体目标如下：(1)比较HIV感染者和非HIV感染者的肺微生物群；(2)确定HIV介导的免疫抑制的程度(即CD4细胞计数)是否与非急性疾病/肺炎的HIV感染者的肺微生物群有关；(3)确定开始抗逆转录病毒治疗和机会性肺炎预防对HIV感染者肺微生物群的影响；(4)确定机会性肺炎和伴随的机会性肺炎治疗对HIV感染者肺微生物群的影响；以及(5)将肺部微生物群的组成和功能与HIV相关的发病率和死亡率联系起来。

DESCRIPTION (provided by applicant): Although the technology to study microbial communities is available, it has yet to be applied comprehensively to the HIV-infected respiratory tract. Our central hypothesis is that the microbiome of the lung is shaped by HIV infection, the degree of HIV-mediated immunosuppression, and the use of antiretroviral and antimicrobial therapies. Furthermore, we hypothesize that the microbiome of the lung changes between periods of health and pneumonia, and that the presence of specific microbes or microbial onsortia within the lung is associated with the development of HIV-associated pulmonary complications and mortality. We propose a series of cross-sectional and longitudinal studies to characterize the bacterial, viral, and fungal microbiome present in the lungs of patients with acute and early HIV infection, chronic HIV infection, and opportunistic pneumonia. We propose to use three microarrays, the 16S rRNA PhyloChip, ViroChip, and 18S rRNA MycoChip as economical, standardized tools to provide a high resolution profile of the microbiome in a large number of HIV patient samples. To complement the microarray analysis and obtain functional profiles of microbial community behavior and associated host response, we will perform next generation 454- pyrosequencing of cDNA generated from a subset of these samples. These studies will be conducted within the Options, SCOPE, and IHOP cohorts, three established and well-characterized cohorts of HIV-infected and HIV-uninfected patients based at SFGH/UCSF. We propose the following specific aims: (1): To compare the lung microbiome in subjects with and without HIV infection; (2): To determine whether the degree of HIV-mediated immunosuppression (i.e., CD4 cell count) is related to the lung microbiome of HIV-infected subjects without acute illness/pneumonia; (3) To determine the effect of initiation of antiretroviral therapy and opportunistic pneumonia prophylaxis on the lung microbiome of HIV-infected subjects over time; (4) To determine the effects of opportunistic pneumonia and accompanying opportunistic pneumonia treatment on the lung microbiome of HIV-infected subjects over time; and (5) To correlate lung microbiome composition and function with HIV-associated morbidity and mortality.