Overview
HIV-associated immune reconstitution inflammatory syndrome (IRIS) is a complication of ART initiation and describes a heterogeneous collection of inflammatory disorders resulting from a robust immune response to an underlying condition.
Etiology
- HIV-associated IRIS has been seen in multiple AIDS-related OIs (especially TB, MAC, Cryptococcus, and CMV) and other infections (such as hepatitis B and C) or inflammatory conditions.
- Risk factors include lower CD4 count and higher viral load at ART initiation as well as rapid increase in CD4 count with treatment.
- There are two categories of IRIS:
- Paradoxical IRIS: clinical deterioration due to worsening of known underlying infection.
- Unmasking IRIS: clinical deterioration due to worsening of previously unrecognized infection.
Evaluation
The clinical features of IRIS vary based on the driving underlying condition. Diagnosis is made from consistent signs or symptoms of the underlying condition with recent ART initiation (with variable timing of onset for different IRIS syndromes). Paradoxical IRIS is a diagnosis of exclusion.
Clinical Characteristics of Common Paradoxical IRIS Syndromes
Pathogen |
Typical Interval |
Incidence |
Typical Presentation |
Mycobacterium avium complex |
1-12 weeks |
30% |
|
Tuberculosis |
1-16 weeks |
15% |
|
CMV retinitis |
4 weeks to 2 years |
15% |
|
Cryptococcal meningitis |
1 week to 3 years |
15% |
|
Pneumocystis pneumonia |
3-6 weeks |
<1%; few well-documented case reports |
|
HBV/HCV |
1-12 weeks |
Unknown |
|
Kaposi sarcoma |
Unknown |
Unknown |
|
Chart from Jacobson MA Diagnosis and Management of Immune Reconstitution Syndrome Associated with Initiation of Antiretroviral Therapy. HIVInSite 2018.
Management
- IRIS management typically involves ART continuation for most cases and targeted treatment of the underlying infection. Please see section Initiation of Antiretrovirals in Acute OI for further guidance on timing for ART initiation following the diagnosis of specific OIs.
- Adjunctive corticosteroid therapy may be considered in cases with severe symptoms.
- Consult an ID specialist for all cases of suspected IRIS.
Key Points
- HIV-associated IRIS represents a heterogeneous collection of inflammatory disorders resulting from a robust immune response to an underlying condition with ART initiation.
- ID should be consulted for all cases of suspected IRIS.
Kenneth H. Mayer, Hans H. Hirsch, Gilbert Kaufmann, Pedram Sendi, Manuel Battegay, Immune Reconstitution in HIV-Infected Patients, Clinical Infectious Diseases, Volume 38, Issue 8, 15 April 2004, Pages 1159–1166, https://doi.org/10.1086/383034
Jacobson MA Diagnosis and Management of Immune Reconstitution Syndrome Associated with Initiation of Antiretroviral Therapy. HIVInSite 2018.
Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on June 1, 2020).