Introduction: Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity in persons living with HIV (PLWH) and HIV appears to uniquely cause COPD, independent of smoking. The mechanisms by which HIV leads to COPD are not clear. The objective of this study was to identify metabolomic biomarkers and potential mechanistic pathways of HIV-associated COPD (HIV-COPD). Methods: We performed case-control metabolite profiling via mass spectrometry in plasma from 38 individuals with HIV-COPD (cases), comparing to matched controls with/without HIV and with/without COPD. Untargeted metabolites of interest were identified with liquid chromatography with mass spectrometry (LC-MS/mass spectrometry (MS)), and targeted metabolomics for tryptophan (Trp) and kynurenine (Kyn) were measured by selective reaction monitoring (SRM) with LC-MS/MS. We used mixedeffects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. Results: We identified 1689 analytes associated with HIV-COPD at a false discovery rate (FDR) of 10%. In PLWH, we identified 263 analytes (10% FDR) between those with and without COPD. LC MS/MS identified Trp and 17 lipids, including sphingolipids and diacylglycerol. After adjusting for relevant covariates, the Kyn/Trp ratio measured by SRM was significantly higher in PLWH (p=0.022), but was not associated with COPD status ( p=0.95). Conclusions: There is a unique metabolite profile in HIV-COPD that includes sphingolipids. Trp metabolism is increased in HIV, but does not appear to independently contribute to HIV-COPD.
Bibliographical noteFunding Information:
Funding The project described was supported by the University of Minnesota Developmental Center for AIDS Research (Research Award). START and its Pulmonary Substudy were funded by the National Heart, Lung and Blood Institute (USA, R01 HL096453), the National Institute of Allergy and Infectious Diseases (USA, UM1AI068641 and UM1AI120197), Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium f|r Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (UK), National Institute for Health Research, National Health Service (UK), and the University of Minnesota. Antiretroviral drugs were donated to the START central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs and Merck. COPDGene was supported by the National Heart, Lung and Blood Institute (USA, R01HL089897 and R01HL089856) and the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion, and GlaxoSmithKline.