Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV

INSIGHT START Pulmonary Substudy Group

Research output: Contribution to journalArticlepeer-review


Chronic obstructive pulmonary disease (COPD) is among the leading causes 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. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to − 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); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. 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. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline. Trial registration: NCT00867048 and NCT01797367.

Original languageEnglish (US)
Article number4749
JournalScientific reports
Issue number1
StatePublished - Dec 2023

Bibliographical note

Funding Information:
KMK reports personal fees from Nuvaira (Independent Data and Safety Monitoring Board; current) and Allergan (consulting; past). RPD reports research grants (awarded to his institution) from ViiV, Gilead and MSD, and participating in advisory commitees from Gilead, ViiV, MSD, Lilly and Theratechnologies. The remaining authors have nothing to declare.

Funding Information:
The START Pulmonary Substudy reported here was supported by the National Heart Lung and Blood Institute (R01 HL096453); the parent START trial was primarily supported by the National Institute of Allergy and Infectious Diseases Division of AIDS (UM1 AI068641 and UM AI120197) with additional support from the German Ministry of Education and Research, the European AIDS Treatment Network (NEAT), the Australian National Health and Medical Research Council, and the UK Medical Research Council and National Institute for Health Research. DMM was supported by NHLBI T32 HL007741 during the conduct of this work. The Veterans Health Administration Office of Research and Development also provided protected research time in support of this study. CHW, EFL, and SS were supported by NHLBI R01 HL140971-01A1. The University of Minnesota served as sponsor of the study. None of the funders nor sponsor had any input regarding the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. This material is also the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center, Minneapolis/USA.

Funding Information:
The study thanks all START Pulmonary Substudy participants for their contributions to our scientific understanding of lung disease in HIV infection. A full listing of START Pulmonary Substudy team members is included in the online supplement (S4) and a full listing of the parent START study team members can be found in the primary START results publication28. We would also like to thank Alan Mickelson for his technical assistance. Disclaimer: The views expressed in this article are those of the authors and do not reflect the views of the United States Government, the National Institutes of Health, the Department of Veterans Affairs, the funders, the sponsors, or any of the authors’ affiliated academic institutions.

Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.


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