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VITAMIN D, D-DIMER, INTERFERON γ, AND SCD14 LEVELS ARE INDEPENDENTLY ASSOCIATED WITH IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME: A PROSPECTIVE, INTERNATIONAL STUDY
Autor
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National Institutes of Health (NIH). National Institute of Allergy and Infectious Diseases (NIAID). Laboratory of Immunoregulation. Bethesda, MD, USA / Duke University. Duke Hubert Yeargan Center for Global Health. Durham, USA
NIAID, NIH. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Sunidade de Medicina Investigativa Salvador, BA, Brasil / Brazilian Institute for Tuberculosis Research. José Silveira Foundation. Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER Initiative). Salvador, BA, Brasil
University of Pennsylvania School of Medicine. Center for Clinical Epidemiology and Biostatistics. Philadelphia, PA, USA
University of Pennsylvania School of Medicine. Center for Clinical Epidemiology and Biostatistics. Philadelphia, PA, USA
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Departamento de Infectología. México, México / Universidad Nacional Autónoma de México. Facultad de Medicina. División de Investigación. Mexico, México
Leidos Biomedical Inc. Reston, VA, USA
University School of Medicine. ,Case Western Reserve. Cleveland, OH, USA
University of Witwatersrand. Johannesburg, South Africa
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Departamento de Infectología. México, México
National Institutes of Health (NIH). National Institute of Allergy and Infectious Diseases (NIAID). Laboratory of Immunoregulation. Bethesda, MD, USA
NIAID, NIH. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Sunidade de Medicina Investigativa Salvador, BA, Brasil / Brazilian Institute for Tuberculosis Research. José Silveira Foundation. Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER Initiative). Salvador, BA, Brasil
University of Pennsylvania School of Medicine. Center for Clinical Epidemiology and Biostatistics. Philadelphia, PA, USA
University of Pennsylvania School of Medicine. Center for Clinical Epidemiology and Biostatistics. Philadelphia, PA, USA
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Departamento de Infectología. México, México / Universidad Nacional Autónoma de México. Facultad de Medicina. División de Investigación. Mexico, México
Leidos Biomedical Inc. Reston, VA, USA
University School of Medicine. ,Case Western Reserve. Cleveland, OH, USA
University of Witwatersrand. Johannesburg, South Africa
Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Departamento de Infectología. México, México
National Institutes of Health (NIH). National Institute of Allergy and Infectious Diseases (NIAID). Laboratory of Immunoregulation. Bethesda, MD, USA
Resumen en ingles
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.
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