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

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.

Inclusion Criteria:

- Subject is Male / Female 18years of age or older.

- Subject has been previously determined to be HIV-infected or is participating in the
The Multicenter AIDS Cohort Study (MACS) or the Women's Interagency Health Study
(WIHS)

Exclusion Criteria:

- Subject is experiencing acute onset of shortness of breath, cough, fevers or heart
conditions problems such as tachycardia, angina or arrhythmias.

- Female subject has told us she is pregnant (this might affect pulmonary function
values,we will not require pregnancy testing.)

- Subject has had an MI, CVA, or cardiovascular event within the past 3 months.

- Subject has had eye or abdominal surgery within past 3 months.

- Active TB by documentation or self reported will be exclusion criteria to the study.

- Subjects will be excluded from the study if they are unable to sign consent, weigh >
300 pounds due to technical difficulties with the CT/EBCT scanner, or have been
exposed to approximately 10 rads in the previous 12 months (i.e., 2 diagnostic CT
scans or 4 cardiac caths or other fluoroscopic exams).