Kimberly F Breglio1, Caian L Vinhaes2,3,4, María B Arriaga2,3,5, Martha Nason1, Gregg Roby1, Joseph Adelsberger6, Bruno B Andrade2,3,4,5,7,8, Virginia Sheikh1, Irini Sereti1. 1. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil. 3. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Salvador, Bahia, Brazil. 4. Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil. 5. Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil. 6. Leidos Biomedical Research Inc, Fredrick National Laboratory for Cancer Research, Frederick, Maryland, USA. 7. Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil. 8. Curso de Medicina, Universidade Salvador, Laureate Universities, Salvador, Bahia, Brazil.
Abstract
BACKGROUND: People with human immunodeficiency virus (HIV) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS. METHODS: People with HIV with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naive patients with CD4 <100 cells/µL. RESULTS: Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower body mass index, lower hemoglobin levels, higher alkaline phosphatase (ALP), and increased CD38 frequency and mean fluorescence intensity on CD8+ T cells at the time of ART initiation compared with non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of ALP and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of ALP at baseline were associated with increased risk of MAC-IRIS development. CONCLUSIONS: High ALP levels and increased CD8+ T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS. Published by Oxford University Press for the Infectious Diseases Society of America 2020.
BACKGROUND: People with human immunodeficiency virus (HIV) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS. METHODS: People with HIV with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naive patients with CD4 <100 cells/µL. RESULTS: Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower body mass index, lower hemoglobin levels, higher alkaline phosphatase (ALP), and increased CD38 frequency and mean fluorescence intensity on CD8+ T cells at the time of ART initiation compared with non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of ALP and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of ALP at baseline were associated with increased risk of MAC-IRIS development. CONCLUSIONS: High ALP levels and increased CD8+ T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS. Published by Oxford University Press for the Infectious Diseases Society of America 2020.
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