Biomarkers of rapid lung function decline in well-controlled HIV and untreated HIV: A secondary analysis of inflammation, coagulation, and pneumoproteins in the START Pulmonary Substudy

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Biomarkers of rapid lung function decline in well-controlled HIV and untreated HIV: A secondary analysis of inflammation, coagulation, and pneumoproteins in the START Pulmonary Substudy

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2021-06

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Background: Chronic obstructive pulmonary disease (COPD) is among the leadingcauses of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. Methods: We performed a matched case:control study of PWH in the Strategic Timingof Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (0 +/- 20 mL/year). The analysis was performed in two distinct groups: 1) those who were virally suppressed for at least 6 months and 2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen). We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. Results: This analysis included 77 matched case:control pairs in the virally suppressedbatch, and 42 matched case:control pairs in the untreated HIV batch (n=238 total). Median (IQR) CD4+ count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. Conclusions: Concentrations of pneumoproteins and biomarkers of inflammation andcoagulation were not associated with subsequent rapid lung function decline.

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University of Minnesota M.S. thesis. June 2021. Major: Clinical Research. Advisor: Ken Kunisaki . 1 computer file (PDF); vi, 38 pages.

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MacDonald, David. (2021). Biomarkers of rapid lung function decline in well-controlled HIV and untreated HIV: A secondary analysis of inflammation, coagulation, and pneumoproteins in the START Pulmonary Substudy. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/258590.

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