Abstract
As a consequence of late presentation for HIV care, a significant proportion of individuals develop immune reconstitution inflammatory syndrome (IRIS) soon after initiation of antiretroviral therapy. Incidence, predictors, and models of pathogenesis of IRIS vary in the literature. Here we discuss factors that may contribute to this lack of consensus. We propose that different pathogens drive different types of IRIS and suggest that these clinical conditions should be studied individually and not grouped under the general heading of “IRIS.”
Highlights
In resource-limited settings, a considerable number of individuals with Human Immunodeficiency Virus-1 (HIV) infection develop immune reconstitution inflammatory syndrome (IRIS) as a consequence of late presentation for HIV care
We revisit the concept that different types of IRIS are determined by the underlying pathogen, and we suggest that these clinical conditions should be studied individually and not grouped under the general concept of “IRIS.” In order to illustrate the differences among these types of IRIS, in which corticosteroids may have profoundly different effects, we reviewed the current literature on tuberculosis-associated IRIS (TB-IRIS) and Kaposi’s sarcoma-associated IRIS (KS-IRIS) in the context of HIV infection
Despite the peak of Th1 cytokines observed during TB-IRIS events [13], reduced concenwww.PaiJournal.com trations of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, IL-3, IL-6, IL-12p40, IL-12p70, IL-15, and IL-17A have been reported before antiretroviral therapy (ART) initiation in individuals developing TB-IRIS compared to controls with TB and HIV coinfection [20]
Summary
In resource-limited settings, a considerable number of individuals with Human Immunodeficiency Virus-1 (HIV) infection develop immune reconstitution inflammatory syndrome (IRIS) as a consequence of late presentation for HIV care. Despite the peak of Th1 cytokines observed during TB-IRIS events [13], reduced concenwww.PaiJournal.com trations of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, IL-3, IL-6, IL-12p40, IL-12p70, IL-15, and IL-17A have been reported before ART initiation in individuals developing TB-IRIS compared to controls with TB and HIV coinfection [20] As most of these cytokines are mainly produced by monocytes, macrophages, and dendritic cells, this scenario is consistent with the notion that aberrant innate immune responses are partially responsible for the impaired pathogen clearance and elevated antigen loads observed in TB-IRIS. Before ART initiation, elevated levels of HIV Tat would promote HHV-8 reactivation Another model proposes that, in individuals with a higher HHV8 dissemination and high HIV load, ART-induced immune reconstitution of HHV-8-specific response may be ineffective in controlling HHV-8 replication, and a cytokine-induced reactive angioproliferation and tumorigenesis might occur, resulting in the development of paradoxical KS-IRIS [36]. The association of LANA with corticosteroid receptors promotes HHV-8 lytic reactivation [51]
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