Immune reconstitution inflammatory syndrome


  • Also called IRIS
  • Definition-Disease or pathogen specific inflammatory response in HIV infected patients after initiation or re-initiation of ARV therapy or after change to more active ARV therapy.
  • Usually low CD4 counts and high viral loads at time of ARV initiation
  • Can occur at any CD4 count
  • Occurs usually within 4-8 weeks after initiation of therapy

Clinical Features

Major Presentations

  • TB- worsening TB symptoms
  • MAC- localized lymphadenitis, pulmonary disease, systemic inflammation indistinguishable from active MAC
    • MAC-IRIS patients are not bacteremic
  • Cryptococcosis- worsening meningitis symptoms
  • CMV- retinitis, vitritis, uveitis
    • IRIS due to CMV can cause vision loss
      • mean time to vitritis 20 weeks
  • Hepatitis B or C- transient transaminitis difficult to distinguish from drug induced cause
    • hepatic flares usually mild, may decompensate cirrhotics.
  • Progressive multifocal leukoencephalopathy- worsening focal neuro lesions, changes on MRI
  • Kaposi's Sarcoma- worsening Kaposi's
  • Autoimmune diseases- Pre-existing autoimmune disorder exacerbation

Minor Presentations

Differential Diagnosis

HIV associated conditions


  • Index of suspicion with known recent initiation of ARV's
  • System specific testing (CXR, LP etc)



  • Standard therapy for offending opportunistic info (i.e. acyclovir for HSV)
  • Largely supportive care
  • Continue ARV except in severe IRIS (see below)

Severe IRIS

  • Defined as a threat to functional status or permanent disability (i.e. vision loss from CMV)
  • Severe IRIS- prednisone 1-2mg/kg (consult HIV/ID) for 1-2 weeks then taper


  • Admit for severe IRIS.
  • Dispo in conjunction with HIV/ID consult.

See Also

External Links



  1. Gutteridge, David L MD, MPH, Egan, Daniel J. MD. The HIV-Infected Adult Patient in The Emergency Department: The Changing Landscape of the Disease. Emergency Medicine Practice: An Evidence-Based Approach to Emergency Medicine. Vol 18, Num 2. Feb 2016.