HIV: Current Research
Open Access

Impacts of Immune Reconstitution Inflammatory Syndrome (IRIS)

Baozhu Zhang^{* *}Correspondence: Baozhu Zhang, Department of Pharmacy, University of Sao Paulo, Butanta, Sao Paulo, Brazil, Email:

Author info »

Description

Immune Reconstitution Inflammatory Syndrome (IRIS) is a condition that occurs in some individuals, typically those with compromised immune systems, who experience a paradoxical worsening of pre-existing infections or the emergence of new inflammatory conditions following the initiation of Anti Retroviral Therapy or other treatments aimed at restoring the immune system. It's most commonly associated with HIV/AIDS, but can also occur in other immunocompromised states, such as after organ transplantation or with certain autoimmune diseases. IRIS was first described in the context of HIV/AIDS, where patients, after starting ART, experienced a sudden and often severe worsening of pre-existing opportunistic infections or the development of new inflammatory conditions. IRIS represents a paradoxical response as the immune system begins to recover and regain its function, it sometimes overreacts to previously undetected pathogens or antigens, causing an inflammatory response.

The pathophysiology of IRIS is complex and not fully understood. However, it's believed to involve a combination of factors, including the restoration of immune responses, dysregulated cytokine production, and the presence of residual antigens from previous infections. In HIV-associated IRIS, the rebound in CD4+ T-cell counts and the restoration of cellular immunity play a central role. The sudden increase in CD4+ Tcells can lead to an exaggerated immune response against opportunistic pathogens. There are two main types of IRIS: paradoxical IRIS and unmasking IRIS. Paradoxical IRIS refers to the worsening of pre-existing infections following immune restoration. Unmasking IRIS occurs when a previously undiagnosed infection becomes apparent as the immune system improves. IRIS can manifest in various ways depending on the underlying condition. Common presentations include worsening of symptoms of pre-existing infections, such as tuberculosis, cryptococcal meningitis, or cytomegalovirus retinitis.

Development of inflammatory conditions like sarcoidosis or autoimmune disorders are symptoms can range from mild to severe and may include fever, lymphadenopathy, respiratory symptoms, neurological deficits, or skin manifestations. Several factors increase the risk of developing IRIS, including severe immunosuppression prior to treatment initiation. High pathogen burden or disseminated infections and short duration between starting ART and onset of IRIS symptoms. Specific pathogens, such as Mycobacterium tuberculosis or Cryptococcus neoformans , are more commonly associated with IRIS. Genetic predisposition or underlying inflammatory conditions may also play a role. Diagnosis of IRIS is primarily clinical and relies on recognizing the temporal association between initiation of immune-restorative therapy and the onset of inflammatory symptoms. Laboratory investigations, including blood tests, imaging studies, and microbiological tests, may help confirm the diagnosis and identify the underlying pathogens.

Management of IRIS involves a multidisciplinary approach aimed at controlling inflammation while minimizing harm to the host. Supportive care to manage symptoms, such as antipyretics for fever and analgesics for pain. Anti-inflammatory agents, including corticosteroids, may be prescribed in severe cases to dampen the immune response. Specific antimicrobial therapy targeting the underlying infection, if identified. In some cases, temporary interruption or modification of immune-restorative therapy may be necessary to mitigate the inflammatory response. The prognosis of IRIS varies depending on various factors, including the underlying condition, severity of symptoms, and promptness of treatment. Most cases of IRIS resolve with appropriate management, although some may require prolonged therapy or result in significant morbidity and mortality, particularly in cases of severe immunosuppression or delayed diagnosis. Early detection and treatment of opportunistic infections before initiating immunerestorative therapy. Close monitoring of patients during the initial phase of treatment for signs of IRIS. Initiating ART in a controlled manner, particularly in patients with advanced HIV disease, to minimize the risk of IRIS. Ongoing research aims to better understand the pathogenesis of IRIS and identify biomarkers that can predict its development. Novel therapeutic approaches, including immunomodulatory agents and targeted therapies, are being investigated to improve outcomes and reduce the morbidity associated with IRIS.

Conclusion

Immune Reconstitution Inflammatory Syndrome represents a unique clinical challenge encountered in the management of immunocompromised individuals, particularly those with HIV/ AIDS. While the exact mechanisms underlying IRIS remain incompletely understood, advances in diagnosis and management have improved outcomes for affected patients.

However, further research is needed to refine our understanding of IRIS pathophysiology and develop more targeted therapeutic interventions to mitigate its impact on patient morbidity and mortality. Effective prevention strategies, early detection, and prompt treatment are crucial in minimizing the adverse effects of IRIS and optimizing the outcomes of immune-restorative therapy.