Epidemiology and Pathogenesis of Pulmonary Hypertension in HIV Patients

描述(申请人提供)：这项研究的目的是描述感染艾滋病毒的个体中的肺动脉高压的流行病学并调查其发病机制。我们的初步数据表明，HIV感染者的临床前肺动脉高压的患病率比之前报道的要高得多，并且与HIV感染独立相关。然而，关于亚临床肺动脉高压的进展、HIV感染者肺动脉压(PAP)升高的自然病史以及HIV相关性肺动脉高压的发病机制，人们知之甚少。我们建议进行一项前瞻性观察队列研究，以描述HIV患者临床前肺动脉高压的自然病史，并确定可检测到的病毒血症与注射用药在肺动脉高压的发生和进展中的相关性(目标1)。此外，我们还将研究HIV-1Nef蛋白和HHV-8感染在HIV携带者肺动脉高压的发生和发展中的机制作用(目标2)。我们还将比较合并和不合并肺动脉高压的HIV感染患者的内皮功能(目标3)。这一应用的优势包括：(1)已经确定了PAP升高的艾滋病毒患者，可以参加这项研究；(2)能够从已经存在的艾滋病毒感染者队列中快速招募受试者；(3)得到旧金山总医院心脏病科和艾滋病毒/艾滋病科的全力支持；(4)科罗拉多大学和宾夕法尼亚州费城的维斯塔尔研究所的高级研究人员的合作。此外，这项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感染者的肺动脉高压的自然历史、病因、发病机制和治疗。公共卫生相关性：这项研究可能会确定临床上有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性肺动脉高压背后的辅助因素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.