Immune reconstitution syndrome

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Immune reconstitution syndrome, or immune reconstitution inflammatory syndrome (IRIS), refers to the paradoxical worsening of pre-existing infections after antiretroviral therapy (ART) is intiated for HIV.[1] It occurs due to increases in T lymphocyte numbers that occurs after ART is started as well as increased immune response.

Clinical Features

Differential Diagnosis

  • Progression of HIV/AIDS
  • Antimicrobial resistance
  • Medication noncompliance
  • Development of new opportunistic infection rather than recrudescence
  • Drug toxicity


Diagnostic Criteria

The diagnosis of IRIS is clinical. Most of the following criteria should be present to make the diagnosis:[3]

  • Presence of AIDS with low pretreatment CD4 count. Usually this is <100, but tuberculosis can be reactivated with CD4 cells >200.
  • Positive virologic and immunologic response to ART
  • Absence of evidence of drug-resistant infection, bacterial superinfection, adverse drug reaction, patient noncompliance, or reduced serum drug levels
  • Presence of clinical manifestations consistent with inflammatory condition
  • Temporal association between ART initiation and the onset of clinical features of illness

Commonly Associated Pathogens


  • Continue ART
  • Treatment of underlying opportunistic infection
  • Glucocorticoids may be indicated as adjunct therapy for severe cases


  • Disposition depends on severity of the immune response as well as the specific underlying disease process. Consider admission if unstable, poor follow-up, or severe illness.

See Also

External Links


  1. DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):447–454. doi:10.7326/0003-4819-133-6-200009190-00013
  2. Cheng VC, Yuen KY, Chan WM, Wong SS, Ma ES, Chan RM. Immunorestitution disease involving the innate and adaptive response. Clin Infect Dis. 2000;30(6):882–892. doi:10.1086/313809
  3. Haddow LJ, Easterbrook PJ, Mosam A, et al. Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. Clin Infect Dis. 2009;49(9):1424–1432. doi:10.1086/630208
  4. Shelburne SA 3rd, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine (Baltimore). 2002;81(3):213–227. doi:10.1097/00005792-200205000-00005