Prevalence and Pathogenesis of Lung Disease in a Large HIV Cohort-coordinating Center

Overview

Despite the availability of highly active antiretroviral therapy (HAART), lung diseases remain a leading cause of morbidity and mortality in those with HIV infection. There have been no large-scale studies detailing pulmonary complications in the HAART era. Substantial gaps exist in our knowledge of the spectrum and pathogenesis of pulmonary disorders in this population, particularly in women and minorities whose numbers with HIV or AIDS have increased. The Multicenter AIDS Cohort Study (MACS) and the Women's Interagency Health Study (WIHS) are prospective, multi-center cohorts that follow approximately 5000 HIV+ subjects and HIV- controls. Although pulmonary disease has not been an area of focus, these established cohorts provide a unique opportunity to systematically study pulmonary complications of HIV infection. Emphysema is of particular interest in the current HIV era because it is likely to increase as this population lives longer with chronic HIV. HIV-infected persons have an increased incidence of emphysema compared to those without HIV infection, and it has been hypothesized that this accelerated disease progression is the result of one or more latent infectious agents that amplify the pulmonary inflammation. Accelerated emphysema was described in HIV infection in a predominantly male population before HAART. The current prevalence and characteristics of HIV-associated emphysema, and the potential impact of gender, have not been rigorously defined.

HIV-infected patients have an increased incidence of emphysema compared to non-HIV-infected patients, and it has been hypothesized that this accelerated disease progression is the result of one or more latent infections that amplifies the pulmonary inflammatory response. We will examine the prevalence and progression of emphysema in subjects with and without HIV and determine risk factors for emphysema in this population. Subjects will be 300 HIV+ subjects and 300 HIV- controls selected by random sampling stratified by age and smoking history. Subjects will be recruited from the University of Pittsburgh and the University of California Los Angles (UCLA) MACS sites. The University of California San Francisco (UCSF) will serve as the recruiting center for the WIHS cohort. Because we are interested in an unbiased estimate of the extent of this disease in HIV infection, we will not select subjects based on lung function or current diagnosis of COPD. The HIV- subjects will be matched to the HIV+ subjects in terms of age and smoking history to the extent possible. Those with symptoms of acute respiratory disease such as fevers, acute change in cough or shortness of breath, or weight loss will be excluded. There will be no exclusions based on HAART use or opportunistic infection (OI) prophylaxis and no exclusions based on previous lung disease as we are trying to obtain a comprehensive evaluation of emphysema in this population as well as identify associated risk factors. All subjects will undergo spirometry, diffusing capacity and quantitative CT scanning. These measurements will allow us to determine differences in the prevalence of emphysema in HIV+ and HIV- and determine risk factors associated with emphysema. For longitudinal studies testing the hypothesis that emphysema is accelerated in HIV infection, we will select HIV+ and HIV- subjects with documented emphysema in each group as defined by diffusing capacity\<80% predicted, post-bronchodilator FEV1/FVC\<70% without significant reversibility, or at least 10% of lung with a density less than -910 Hounsfield units (HU). These subjects will have CT scans and PFTs at baseline and at 18 months and 36 months after baseline. At each visit, clinical data and biological samples will be collected.