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Abstract
Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations.
Highlights
Mycobacterium tuberculosis infection (TB) remains the world’s most deadly infectious disease with 10 million cases and nearly 1.5 million deaths in 2018 alone [1]
While TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) may occur in settings outside of HIV co-infection, the focus of this review relates to HIV [9]
While neurologic worsening after Antiretroviral therapy (ART)-initiation in a patient being treated for TB meningitis (TBM) is strongly indicative of central nervous system (CNS)-TB-IRIS, several other conditions should be considered
Summary
Mycobacterium tuberculosis infection (TB) remains the world’s most deadly infectious disease with 10 million cases and nearly 1.5 million deaths in 2018 alone [1]. An important complication of TB-HIV coinfection in the post-ART era is TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Unmasking TB-IRIS is ART-associated TB that occurs within three months of ART initiation and has a “heightened intensity of clinical manifestations, if there is evidence of a marked inflammatory component”. But are not limited to, lymphadenitis, abscesses, respiratory failure, or a systemic inflammatory syndrome In this case TB was not diagnosed or treated prior to initiation of ART [4]. The definition for paradoxical IRIS is well characterized and has been widely used, but the definition for unmasking IRIS remains provisional due to an unclear delineation of the inflammatory characteristics required, and the term “ART-associated TB” has been used to include unmasking IRIS as well as non-IRIS TB diagnosed after ART initiation [4]. While TB-IRIS may occur in settings outside of HIV co-infection (for example, with a decrease in immune suppressive medications related to transplantation), the focus of this review relates to HIV [9]
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