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AN INFLAMMATORY COMPOSITE SCORE PREDICTS MYCOBACTERIAL IRIS IN PEOPLE WITH HIV AND SEVERE LYMPHOPENIA: A PROSPECTIVE INTERNATIONAL COHORT STUDY
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Background: Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with HIV (PWH) who initiate 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 antiretroviral therapy (ART)-naïve PWH with severe immunosuppression (CD4+ count <100 cells/mm³) in US, Kenya and Thailand (NCT00286767). 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 (IL-6, IL-10, IL-27, sCD14, IFN-γ, TNF-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.
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