NCT03572335

Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)

Systems Biology of Diffusion Impairment in HIV--BoDI

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 61 (actual)
• Sponsor: University of Pittsburgh · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Diffusing capacity for carbon monoxide (DLco) abnormalities are common in HIV+ individuals and associated with significant morbidity and mortality. The complexity and the individualized differences in causes of these abnormalities have been challenging to unravel using traditional approaches. In this proposal, the investigators construct a systems' modeling approach to identify novel molecular and clinical pathways contributing to DLco impairment in HIV+ individuals and to determine predictive signatures of DLco decline in order to develop strategies to treat and prevent abnormal lung function in this susceptible population.

Detailed description

Mechanisms of impairment of diffusing capacity for carbon monoxide (DLco), which affects over 50 percent of HIV+ individuals, are poorly understood. No therapies exist despite significant impact on quality of life and mortality. Identifying molecular pathways of DLco impairment in HIV+ individuals and developing ability to predict HIV+ individuals at risk of DLco impairment is thus of utmost importance for improving care. In this proposal, the investigators construct a systems' modeling approach to identify molecular and clinical pathways contributing to DLco impairment in HIV+ individuals. The investigators collect multiple parallel molecular datasets integrated with detailed pulmonary function, radiographic, and echocardiographic measurements to build a comprehensive, systems level model of DLco abnormalities in HIV and to develop predictive models of susceptibility to DLco worsening. As our preliminary data suggest that certain micro ribonucleic acid (miRNAs), such as the hypoxia-induced and metabolically active gene (miR-210), may play an important role in DLco abnormalities in HIV, the investigators then perform hypothesis-testing experiments to determine the impact of miRNAs on lung epithelial and endothelial cells. The investigators will utilize a well phenotyped cohort of over 500 HIV+ individuals with associated biospecimens to execute the aims. Participants identified to already have specimens available will be scheduled to have PFT testing, bronchoscopy including bronchial wash with brushes and blood collection.

Conditions

• HIV Infections
• Pulmonary Disease

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	PFT's (pulmonary function testing)	The routine lung function endpoints of FVC(forced vital capacity), FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder before and after bronchodilator administration. The system is calibrated for body temperature and pressure of saturated gas and volumes, per American Thoracic Society (ATS) standards . DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms with ATS standards.

Timeline

• Start date: 2018-09-06
• Primary completion: 2022-10-01
• Completion: 2024-08-01
• First posted: 2018-06-28
• Last updated: 2025-03-07

Locations

1 site across 1 country: United States