title: Vitamin D, D-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study.
abstract: To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA; Duke Hubert Yeargan Center for Global Health, Duke University, 310 Trent Drive, Duke Box 90518, Durham, NC 27708, USA.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Musselwhite
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, NIH, 50 South Drive, Bethesda, MD 20892, USA; Unidade de Medicina Investigativa, Laboratório Integrado de Microbiologia e Imunorregulação (LIMI), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER Initiative), Brazilian Institute for Tuberculosis Research, José Silveira Foundation, Salvador, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 611 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-602, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 611 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-602, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Tierney
authors.affiliation: Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México City, México; División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México.
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Belaunzaran-Zamudio
authors.affiliation: Leidos Biomedical Inc., 11951 Freedom Drive, Reston, VA 20190, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.affiliation: Case Western Reserve University School of Medicine, 2061 Cornell Rd, Cleveland, OH 44106, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México City, México.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Sierra Madero
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood* / Q000209:etiology; D007371:Interferon-gamma / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D018417:Th1 Cells / Q000276:immunology; D014807:Vitamin D / Q000097:blood*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018950:Lipopolysaccharide Receptors; C036309:fibrin fragment D; D014807:Vitamin D; D007371:Interferon-gamma
keywords: Biomarker; HIV; IRIS; Inflammatory cytokine; Vitamin D; d-Dimer