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Clinical Summary

Effective antiretroviral therapy (ART) for HIV establishes virologic suppression and can allow the patient’s immune system to rebuild to a near-normal competency. In some patients who develop a rapid immune response following ART initiation after a very advanced degree of immune suppression, the immune reconstitution inflammatory syndrome (IRIS) can develop. In these patients, it is thought that previously subclinical infections manifest with the development of a more robust immune status. IRIS is most often seen in patients who have recently started ART (usually within 60 days of starting therapy) with an initial CD4 count below 100 cells/mm3. The most common infections that can “trigger” IRIS include Mycobacterium (tuberculosis and Mycobacterium avium complex [MAC]), cytomegalovirus (CMV), cryptococcal disease, and histoplasmosis. Patients typically present with fever, malaise, lymphadenopathy, and symptoms associated with the active opportunistic infection.

Management and Disposition

The key for the ED physician is to identify patients who have recently started ART and may be presenting with IRIS-related findings. Appropriate evaluation and management depend on the underlying opportunistic infection. Patients will often require admission to the hospital and consultation with an infectious diseases specialist.


  1. HIV-infected patients who are currently taking ART and present with a febrile illness should be questioned regarding the duration of ART and pretreatment CD4 count. Patients with advanced disease who have recently started ART may be presenting with signs and symptoms of IRIS-related disease.


IRIS. This patient presented with fever and diffuse lymphadenopathy secondary to MAC infection. The patient had no manifestations of his disseminated disease until being started on antiretroviral therapy. (Photo contributor: Stephen P. Raffanti, MD.)

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