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 |
|
Mycobacteria |
||
|
Mycobacterium avium complex |
Initial presentation or exacerbation of MAC disease, eg. fever, lymphadenitis |
MAC-IRIS |
|
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 |
BCG-IRIS |
|
Fungi |
||
|
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 |
PJP-IRIS |
|
Viruses |
||
|
Cytomegalovirus |
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 |
KS-IRIS |
|
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 |
PML-IRIS |
|
Hepatitis B virus |
Hepatitis flare |
HBV-IRIS |
|
Hepatitis C virus |
Hepatitis flare |
HCV-IRIS |
|
Protozoa |
||
|
Toxoplasma gondii |
Initial presentation or exacerbation of Toxoplasma encephalitis |
TE-IRIS |
|
Uncertain pathogens |
||
|
Lymphoma presentation after commencing ART |
||
- Many other pathogens have also been associated with the development of an IRIS.