reaction is usually self-limited, especially if the preexisting infection is effectively treated. However, long-term sequelae and fatal outcomes may rarely occur, particularly when neurologic structures are involved.Diagnostic criteria for IRISo There is no universally agreed-upon definition for IRIS. However, it is generally accepted that the diagnosis of IRIS requires the worsening of a recognized (''paradoxical" IRIS) or unrecognized pre-existing infection ("unmasking" IRIS) in the setting of improving immunologic function.Most or all of the following features should be present in order to make the diagnosis:o The presence of AIDS with a low pretreatment CD4 count (often less than 100 cells/microL). One important exception to this general rule is tuberculosis. IRIS secondary to preexisting M. tuberculosis infection may occur in individuals with CD4 counts >200.o A positive virologic and immunological response to ART.o The absence of evidence of drug-resistant infection, bacterial superinfection, drug allergy or other adverse drug reactions, patient noncompliance, or reduced drug levels due to drug-drug interactions or malabsorption after appropriate evaluation for the clinical presentation.o The presence of clinical manifestations consistent with an inflammatory condition.o A temporal association between HAART initiation and the onset of clinical features of illness.Summary and recommendationso The clinical features of each individual case of IRIS are highly variable and data from controlled trials have not been published thus far to provide clear guidelines. Our recommendations are based on clinical experience, case reports, case series, and expert opinion:# Although it is reasonable to perform studies looking for unmasked subclinical opportunistic infection, the diagnosis of IRIS is generally one of exclusion. Investigations to rule out the possibility of drug reaction, patient noncompliance, persistently active infection and/or drug resistance are usually warranted before concluding that IRIS is present.# Most patients with IRIS develop symptoms within one week to a few months after the initiation of HAART. With later onset, other diagnoses become more likely. Abacavir hypersensitivity can be confused with IRIS, but symptoms worsen soon after each dose of abacavir. The diagnostic work-up for abacavir hypersensitivity reaction includes genetic testing for HLA-B5701.# When a diagnosis of IRIS is considered highly likely, further or repeated invasive diagnostic procedures to locate an occult infection may be reasonably delayed, deferred, or altogether avoided.# Treatment for the underlying pathogen should generally be started or continued in patients who develop IRIS. This is particularly important when treating patients with IRIS associated with hepatitis B virus.# Corticosteroids or NSAIDS may help decrease the inflammatory response in some patients with IRIS. The decision to use corticosteroids should be individualized and should take into account the risks of therapy. When we choose to treat with corticosteroids, we initiate therapy with prednisone at a dose of 1 mg/kg/day (maximal dose 60 to 80 mg) and then taper steroid therapy while monitoring for recurrence of clinical symptoms over the ensuing weeks to months.# For most patients, we suggest initiation of ART within two weeks of starting treatment of the underlying opportunistic infection to decrease the risk of clinical progression of AIDS and death.# For OIs that lack proven effective therapies other than HAART (eg, PML), we believe it is best to treat these patients with HAART despite the risk of an adverse outcome. We normally do not use steroids in such patients unless or until symptoms of IRIS appear.">