Epidemiology and Pathogenesis of Pulmonary Hypertension in HIV Patients

描述（由申请方提供）：本研究的目的是描述HIV感染者肺动脉高压的流行病学，并研究其发病机制。我们的初步数据表明，HIV感染个体的临床前肺动脉高压患病率远高于以往报道，且与HIV感染独立相关。然而，关于亚临床肺动脉高压的进展、HIV感染个体中肺动脉压（PAP）升高的自然史或HIV相关肺动脉高压的发病机制知之甚少。我们建议进行一项前瞻性观察性队列研究，以描述HIV患者临床前肺动脉高压的自然史，并确定可检测的病毒血症与肺动脉高压发生和进展中注射药物使用之间的相关性（目的1）。此外，我们将研究HIV-1 Nef蛋白和HHV-8感染在HIV感染者肺动脉高压发生和进展中的机制作用（目的2）。我们还将比较有和没有肺动脉高压的HIV感染患者的内皮功能（目的3）。该申请的优势包括（1）已经确定了PAP升高的HIV患者入组研究（2）能够从现有的HIV感染受试者队列中快速招募受试者（3）San弗朗西斯科总医院心脏科和HIV/AIDS科的全力支持;以及（4）科罗拉多大学和宾夕法尼亚州费城Wistar研究所的高级研究人员的合作。此外，本研究中收集的临床数据库、血清和血浆库以及超声心动图和血流动力学数据将为未来的合作努力提供基础，以更好地了解HIV感染者肺动脉高压的自然史、病因、发病机制和治疗。公共卫生相关性：这项研究将有可能识别出有临床肺动脉高压风险的患者，并允许临床医生提前干预治疗。此外，更多地了解艾滋病毒相关肺动脉高压背后的辅助因子和病理生理学可能会导致未来新疗法的开发。

DESCRIPTION (provided by applicant): The purpose of this study is to describe the epidemiology of pulmonary hypertension in individuals with HIV infection and to investigate its pathogenesis. Our preliminary data suggest that the prevalence of pre- clinical pulmonary hypertension in individuals with HIV infection is much higher than previously reported and is independently associated with HIV infection. However, very little is known about the progression of sub- clinical pulmonary hypertension, the natural history of elevated pulmonary arterial pressure (PAP) in HIV- infected individuals, or the pathogenesis of HIV-associated pulmonary hypertension. We propose to conduct a prospective observational cohort study to describe the natural history of pre- clinical pulmonary hypertension in patients with HIV and to determine the association between detectable viremia and injection drug use in the development and progression of pulmonary hypertension (Aim 1). In addition, we will investigate the mechanistic role of the HIV-1 Nef protein and HHV-8 infection in the development and progression of pulmonary hypertension in individuals with HIV (Aim 2). We will also compare endothelial function in HIV-infected patients with and without pulmonary hypertension (Aim 3). Strengths of this application include (1) having already identified HIV patients with elevated PAP to enroll into the study (2) the ability to rapidly recruit subjects from already existing cohorts of HIV-infected subjects (3) the full support of the Cardiology Division and the HIV/AIDS Division at San Francisco General Hospital; and (4) the collaboration of senior investigators at the University of Colorado and The Wistar Institute, Philadelphia, PA. In addition, the clinical databases, serum and plasma banks, and echocardiographic and hemodynamic data collected in this study will provide the basis for future collaborative efforts to better understand the natural history, etiology, pathogenesis, and treatment of pulmonary hypertension in individuals with HIV infection. Public health relevance: This study will potentially identify patients at risk for clinical pulmonary hypertension and allow clinicians to intervene with therapy beforehand. In addition, understanding more about the cofactors and pathophysiology behind HIV-associated pulmonary hypertension may lead to the development of new therapies in the future.