Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV
Authors: MacDonald David M. , Samorodnitsky Sarah , Wendt Chris H. , Baker Jason V. , Collins Gary , Kruk Monica , Lock Eric F. , Paredes Roger , Poongulali Selvamuthu , Weise Danielle O. , Winston Alan , Wood Robin , Kunisaki Ken M. ,   INSIGHT START Pulmonary Substudy Group,   International Coordinating Centres, Aagaard B. , Jansson P. O. , Pearson M. T. , Babiker A. G. , Arenas-Pinto A. , Atako N. B. , Dennis E. , Forcat S. , Hudson F. , Jackson B. , Maas D. , Purvis C. , Russell C. , Emery S. , Carey C. , Clewett M. , Jacoby S. , Gordin F. , Vjecha M. , Sanchez A. ,   Site Coordinating Centres, Loria G. R. , Doldan M. L. , Moricz A. , Tillmann K. , Müller V. , Touloumi G. , Gioukari V. , Anagnostou O. , Herrero P. , Lopez P. , Avihingsanon A. , Rerksirikul P. ,   Site Investigators by Country and institution, Loiza E. , Mingrone V. , Lupo S. , Marconi F. , Daniel D. , Crinejo A. , French M. , Barba L. , Rowling D. , Warzywoda E. , Bloch M. , Agrawal S. , Dwyer D. , Taylor J. , van Petersen L. , Mertens L. , De Wit S. , Kabamba K. , Wolff M. , Allendes G. , Ristola M. , Debham O. , Jessen H. , Jessen A. , Wiebecke S. , Klinker H. , Fätkenheuer G. , Lehmann C. , Knaevelsrud I. , Rittweger M. , Stöhr A. , Olah K. , Schaaf B. , Hower M. , Harrer T. , Harrer E. , Skoutelis A. , Papastamopoulos V. , Metallidis S. , Tsachouridou O. , Pujari S. , Chitalikar A. , Kumarasamy N. , Beulah F. , Shahar E. , Kedem E. , Turner D. , Madero J. Sierra , Madrigal C. , Filali K. M. El , Erradey I. , Ekong E. , Eriobu N. , Valencia J. , León M. , Montalbán E. , Alave J. , Salazar R. , Vega J. , del Portal M. , Mendo F. , Bakowska E. , Ignatowska A. , Czarnecki M. , Szymczak A. , Wood R. , Rattley M. , Pillay S. , Mngqibisa R. , Ndaba T. , Madlala P. , Estrada V. , Rodrigo M. , Gutierrez M. , Muñoz J. , Dalmau D. , Badia C. , Clotet B. , Llibre J. M. , Ruxrungtham K. , Gatechompol S. , Kiertiburanakul S. , Sanmeema N. , Bowonwatanuwong C. , Ampunpong U. , Prasithsirikul W. , Thongyen S. , Chetchotisakd P. , Anunnatsiri S. , Ratanasuwan W. , Werarak P. , Kityo C. , Mugerwa H. , Munderi P. , Lutaakome J. , Clarke A. , Bexley A. , Das S. , Sahota A. , Emerson C. , McKernan S. , Johnson M. A. , Youle M. , Ross J. , Harding J. , Kegg S. , Moussaoui T. , Chen F. , Lynch S. , de Burgh-Thomas A. , Karunaratne I. , Dockrell D. , Bowman C. , Winston A. , Mora-Peris B. , Chadwick D. R. , Lambert P. , Desai N. , Carter W. , Henry K. , Givot R. , Chow M. , Holloway B. , Weis S. , Vecino I. , Novak R. , Culbert G. , Wilkin A. , Mosley L. , Thielman N. , Granholm J. , Watson V. , Clark C. , Santana J. , Boneta I. , Brar I. , Makohon L. , MacArthur R. , Farrough M. , Frank M. , Parker S. , Tedaldi E. , Santiago M. , Koletar S. , Harber H. , Thomas D. , Bica I. , Adams B. , Van Dam C. , Kolber M. , Moreno K. , Brown A. , Wade B. 
Published: March 2023

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.