TABLE 2.

LONGITUDINAL STUDIES OF HIV-ASSOCIATED LUNG INFECTIONS AND COMPLICATIONS (RFA: HL07-008): OVERVIEW OF PROJECTS BY CLINICAL CENTER

Clinical Center	Study	Goal/Intervention	Enrollment Sites; Date Enrollment Began	Affiliated Cohort Study	Patient Population
1	Longitudinal Evaluation of Lung Health in a Woweto Cohort of HIV-infected Adults (PI, Richard Chaisson; co-PI, Neil Martinson)	1. Establish a database and tissue repository from a clinical cohort of HIV-infected South Africans. 2. Assess the epidemiology, natural history, and clinical course of AIDS-associated lung diseases longitudinally.	South Africa; 11/2008	HIV Wellness Cohort, Soweto; Novel TB preventive Therapy Study Cohort (44, 45)	1,000 HIV+ adults from Soweto, South Africa: 500 from previous RCT of TB preventive therapy regimens, 500 from HIV Wellness Clinics
2	Study of HIV Infection in the Etiology of Lung Disease (SHIELD) (PI, Gregory Kirk)	1. Investigate the prevalence or incidence and risk factors for noninfectious lung disease, including COPD, lung cancer, and pulmonary arterial hypertension.	USA; 12/2008	Three affiliated HIV cohort studies in Baltimore: AIDS Linked to the IntraVenous Experience (ALIVE), Johns Hopkins HIV Clinical Cohort (JHHCC), Study to Help the AIDS Research Effort (SHARE) (46–48)	Approximately 3,500 HIV+ outpatients enrolled in parent cohort studies; 450 of these enrolled in focused COPD and 750 in PAH studies
3	Longitudinal Studies of HIV-Associated Bacterial Pneumonia (PI, William Rom)	1. Follow 400 HIV+ subjects for bacterial pneumonia. 2. Evaluate BAL and peripheral blood specimens for differences in cytokines, cell surface molecules, and HIV replication and mutations.	USA and South Africa; 10/2008	N/A	400 HIV+ subjects enrolled. Bacterial pneumonia diagnosed in ∼36 patients at each site lavaged for mechanistic studies focused on HIV and bacterial pneumonia. Two control HIV+ patients lavaged at the same time for studies on lung HIV, neutrophils, and alveolar macrophages.
4	Smoking Cessation and the Natural History of HIV-associated Emphysema (PI, Philip Diaz)	1. Examine the effects of smoking cessation on respiratory symptoms, pulmonary function and alveolar macrophage biology in a cohort of HIV+ smokers.	USA; 9/2008	N/A	365 HIV+ current smokers
5	International HIV-associated Opportunistic Pneumonias (IHOP) Study (PI, Laurence Huang)	1. Determine the frequency and mortality of HIV-associated opportunistic pneumonias. 2. Evaluate the sensitivity and specificity of molecular tools for PCP and pulmonary TB diagnosis. 3. Determine the frequency of Pneumocystis dihydropteroate synthase (DHPS) gene mutations and study putative mechanisms for trimethoprim-sulfamethoxazole drug resistance.	USA, Uganda; 10/2008	N/A	2,400–3,000 HIV+ inpatients with suspected pneumonia
6	Longitudinal Studies of HIV-1 Nef in Pulmonary Hypertension (PI, Sonia Flores)	1. Determine if particular HIV Nef signature sequences are associated with and predict HIV-related pulmonary hypertension.	France, USA; 12/2008	N/A	80 HIV+ patients with PAH and 60 HIV+ patients without PAH
7	Prevalence & Pathogenesis of Pulmonary Disease in a Large Multicenter HIV Cohort (PI, Alison Morris)	1. Describe epidemiology and risk factors for pulmonary disease in the current era.	USA; 8/2008	Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohorts (48, 49)	4000 HIV+ and HIV− outpatients enrolled in MACS and WIHS, with 600 of these enrolled in emphysema studies
		2. Determine if COPD is more prevalent and progresses more quickly in those with HIV infection compared with control subjects.
		3. Evaluate the role of infections in HIV-associated COPD.
8	Investigations in HIV Associated Lung Events (INHALE) and Examinations of HIV Associated Lung Emphysema (EXHALE) Studies (PI, Kristina Crothers)	1. Understand the epidemiology of lung diseases in HIV, and smoking as a risk factor 2. Compare clinical and pathophysiologic differences in COPD and decline in pulmonary function between HIV+ and HIV− patients	USA;12/2008	Veterans Aging Cohort Study (VACS) (50)	Approximately 3,500 HIV+ and 3,500 HIV− veterans enrolled in VACS for INHALE; with 180 HIV+ and 180 HIV−participants with or at risk for COPD prospectively enrolled in EXHALE; those with lung diseases other than COPD are excluded from EXHALE.

Definition of abbreviations: BAL = bronchoalveolar lavage; COPD = chronic obstructive pulmonary disease; HIV+ = HIV-infected; HIV− = HIV-uninfected; PAH = pulmonary arterial hypertension; PCP = Pneumocystis pneumonia; PI = principal investigator; RCT = randomized controlled trial; TB = tuberculosis.