Clinical presentation of an IRIS

An IRIS mostly occurs between 2 weeks and 3 months after ART commencement or ART intensification but may occur earlier (within days) and as late as a year after treatment. Temporal onset of an IRIS is particularly difficult to attribute in patients with erratic ART adherence. Typically, IRIS patients had a very low CD4+ T cell count when ART was commenced and present with fever and exaggerated or atypical clinical manifestations of an HIV-related infection or cancer. Practically, any chronic viral, mycobacterial, fungal or protozoan infection that is usually controlled by cellular immune responses may be associated with an IRIS (Table 1). Further information on clinical characteristics of different types of IRIS is available elsewhere (26).

Table 1. The most common types of immune reconstitution inflammatory syndrome that may occur in very immunodeficient HIV patients after commencing ART1

Pathogens associated with an IRIS

Clinical characteristics

Common abbreviations


Mycobacterium avium complex

Initial presentation or exacerbation of MAC disease, eg. fever, lymphadenitis


Mycobacterium tuberculosis

Initial presentation or exacerbation of TB, eg. fever, lymphadenitis, pneumonitis, pleural or pericardial effusions, meningoencephalitis

TB-IRIS or TBM-IRIS when meningitis is the only clinical manifestation

Bacille Calmette-Guerin

Regional lymphadenitis



Cryptococcus neoformans

Initial presentation or exacerbation of cryptococcal meningoencephalitis

C-IRIS or CM-IRIS when meningitis is the only clinical manifestation

Pneumocystis jirovecii

Exacerbation of pneumonitis




CMV retinitis presenting after commencement of ART

CMV immune recovery retinitis

Uveitis after previously treated CMV retinitis

IRU (immune recovery uveitis)

Kaposi’s sarcoma-associated herpesvirus

Initial presentation or exacerbation of KS


Varicella zoster virus

Dermatomal or multidermatomal zoster

Rarely, myelitis or encephalitis

Herpes simplex virus

Genital or oral herpes with atypical inflammation

Rarely, myelitis or encephalitis

JC virus

Initial presentation or exacerbation of PML with inflammatory characteristics


Hepatitis B virus

Hepatitis flare


Hepatitis C virus

Hepatitis flare



Toxoplasma gondii

Initial presentation or exacerbation of Toxoplasma encephalitis


Uncertain pathogens

Lymphoma presentation after commencing ART

  1. Many other pathogens have also been associated with the development of an IRIS.