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The  term “ Immune Reconstitution Inflammatory Syndrome ” (IRIS) also “ Immune Restoration Disease” describes a collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious processes following the initiation of antiretroviral therapy(ART) in HIV infected individuals. In HIV infection, an exaggerated inflammatory reaction to a disease causing microorganism that sometimes occur when the immune system begins to recover following treatment with ART drugs. IRIS occurs in two forms.

Ø Unmasking (unrecognized) IRIS refer to the flare-up of an underlying , previously undiagnosed infection soon after ART is started.

Ø Paradoxical (recognized) IRIS refers to the worsening of previously treated infection after ART is started.

HIV infection produces both quantitative & qualitative time- dependent deleterious effects on  immune   system. Most patients with IRIS develop symptoms within one week to few months after the initiation of ART. Clinical features of IRIS strongly related to type & location of pre-existing opportunistic infection. Patients should be treated for the underlying opportunistic infection as soon as possible. Adjunctive therapies ,such as glucocorticoids may also needed in certain settings.

Criteria for IRIS Diagnosis:-

There is no universally agreed upon definition for IRIS. However generally accepted diagnosis of IRIS requires the worsening of a recognized or unrecognized pre-existing infection in the setting of improving immunologic function. Features to make diagnosis:

Ø The presence of AIDS with a low pre-treatment CD4 count (less than100 cells/microL)

Ø A positive virologic & immunological response to ART

Ø The absence of evidence of drug –resistant infection, bacterial superinfection, drug allergy or other adverse drug reactions, patient noncompliance, malabsorption after appropriate evaluation for the clinical presentation.

Ø The presence of clinical manifestations consistent with an inflammatory condition.

Ø A temporal association between ART initiation & onset of clinical features of illness.

The Pathogens Associated with IRIS:-

Ø Mycobacterium tuberculosis

Ø Mycobacterium avium complex

Ø Cytomegalovirus

Ø Cryptococcus neoformans

Ø Herpes simplex virus

Ø Pneumocystis jirovecii

Ø Hepatitis B virus

Treatment guideline generally recommend initiating ART within two weeks for most opportunistic infections. Exceptions to this includes Cryptococcal meningitis & tuberculosis meningitis, in that case benefits of ART may outweighed by induction of a potentially serious immune reconstitution inflammatory syndrome.