Caian L Vinhaes1,2,3, Virginia Sheikh4, Deivide Oliveira-de-Souza1,2,3, Jing Wang4, Adam Rupert4, Gregg Roby4, María B Arriaga1,2,5, Kiyoshi F Fukutani1,2, Fred Sawe6, Doug Shaffer6, Jintanat Ananworanich7, Nittaya Phanuphak8, Bruno B Andrade1,2,3,5,9,10, Irini Sereti4. 1. Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. 2. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Brazil. 3. Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil. 4. National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 5. Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil. 6. Kenya Medical Research Institute, Henry Jackson Foundation Medical Research International, Bethesda, Maryland, USA. 7. South East Asia Research Collaboration with Hawaii, Henry M. Jackson Foundation for the Advancement of Military Medicine, United States Military HIV Research Program, Bethesda, Maryland, USA. 8. Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 9. Universidade Salvador, Laureate Universities, Salvador, Brazil. 10. Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management. METHODS: Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model. RESULTS: We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort. CONCLUSIONS: Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART. CLINICAL TRIALS REGISTRATION: NCT00286767.
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management. METHODS: Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model. RESULTS: We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort. CONCLUSIONS: Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART. CLINICAL TRIALS REGISTRATION: NCT00286767.
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