What is Immune Reconstitution Inflammatory Syndrome (IRIS)?

From the Guidelines

Immune Reconstitution Inflammatory Syndrome (IRIS) is a condition that occurs in HIV-infected patients, typically after starting antiretroviral therapy (ART), characterized by a paradoxical worsening of symptoms, signs, or clinical manifestations of an opportunistic infection, such as tuberculosis or Kaposi sarcoma, due to the reconstitution of immune responsiveness.

Key Characteristics of IRIS

• Typically occurs within 3 to 6 months after starting ART 1
• Characterized by marked lesional swelling, increased tenderness, and peripheral edema in patients with Kaposi sarcoma 1
• May include high fevers, worsening respiratory symptoms, increase in size and inflammation of involved lymph nodes, new lymphadenopathy, expanding central nervous system lesions, worsening of pulmonary parenchymal infiltrations, new or increasing pleural effusions, and development of intra-abdominal or retroperitoneal abscesses in patients with tuberculosis 1
• Can be mild to moderate in severity, but may also be severe and life-threatening, especially in patients with CNS tuberculosis 1

Risk Factors for IRIS

• Earlier ART initiation and CD4+ cell counts <50 cells/μL 1
• Concurrent or recent use of glucocorticoids and/or advanced immunosuppression 1
• Pulmonary involvement in patients with Kaposi sarcoma 1

Management of IRIS

• Symptomatic management, with continuation of ART and anti-tuberculosis therapy, and addition of anti-inflammatory agents such as ibuprofen for mild cases 1
• Corticosteroids, such as prednisone 1.25 mg/kg/day, may be effective for more severe cases of IRIS, but are contraindicated in Kaposi sarcoma-associated IRIS due to the potential for life-threatening exacerbation 1
• Drainage may be necessary for patients with worsening pleural effusions or abscesses 1

From the Research

Definition of Immune Reconstitution Inflammatory Syndrome (IRIS)

• IRIS is characterized by worsening clinical, laboratory, or radiologic findings despite improvements in the HIV RNA level and CD4 count after the introduction of antiretroviral therapy 2
• It is due to the restoration of pathogen-specific immune responses and may occur during or shortly after the treatment of an opportunistic infection or as a "new" clinical syndrome resulting from a previously unrecognized occult infection 2

Clinical Presentations of IRIS

• IRIS is best considered a group of disorders with a wide range of clinical manifestations, incorporating disease resulting from pathological inflammation to pathogens, immune-mediated inflammatory disease, and autoimmune disease 3
• Clinical effects range from a mild, self-limiting illness to severe morbidity and mortality 3
• The clinical presentation of IRIS involves the unmasking of covert infections or the worsening of overt conditions, and its manifestations depend on the trigger antigen, which can be an infective agent, a host antigen, or a tumor antigen 4

Risk Factors for IRIS

• Risk factors for IRIS include a low CD4 count, the presence of latent infection(s), and a robust virologic and immunologic response to HAART 2
• The development of IRIS is independently associated with using a boosted protease inhibitor, a nadir CD4 count <100 cells/mm(3), and a plasma HIV viral RNA decrease of more than 2.5 log at the time of IRIS compared with RNA levels before the initiation of HAART 5
• Risk for IRIS is enhanced in those with low CD4 counts and preexisting opportunistic infections 6

Treatment and Management of IRIS

• The prognosis for most IRIS cases is favorable because a robust inflammatory response may predict an excellent response to HAART in terms of immune reconstitution and, perhaps, improved survival 2
• Most IRIS cases are self-limiting, but a few cases can be overwhelming and life-threatening; hence, early recognition is important 4
• Treatment options include pathogen-specific therapy, antiinflammatory therapies, and other novel approaches 6