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Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS

Outcome and epidemiology

From the Department of Medicine (J.A.M., F.G.M., S.H., C.P.), University of Alberta, Edmonton; and Departments of Pathology and Laboratory Medicine (R.N.A.) and Microbiology and Infectious Diseases (M.J.G., C.P.), University of Calgary, Alberta, Canada.

Address correspondence and reprint requests to Dr. Christopher Power, Department of Medicine (Neurology), 6-11 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada AB T6G 2S2 chris.power{at}ualberta.ca.

Objective: To characterize the immune reconstitution inflammatory syndrome in the nervous system (NeuroIRIS) among patients with HIV/AIDS.

Background: NeuroIRIS has been recognized as a complication of combination antiretroviral therapy (cART).

Methods: A retrospective analysis was performed of NeuroIRIS patients fulfilling diagnostic criteria and followed at the Northern or Southern Alberta (HIV) Clinics. A nested epidemiologic study was performed within a subset of patients in whom cART was started from 1999 to 2007.

Results: NeuroIRIS was diagnosed in seven patients initiating cART. All were men (median age, 35 years) and exhibited severe immunosuppression (median CD4⁺ T cells, 30 cells/mm³). Four patients presented to the Southern Alberta Clinic, representing all NeuroIRIS cases among 461 patients in whom cART was initiated over an 8-year period (incidence 0.9%). New onset of neurologic deterioration (n = 4) or worsening of prior neurologic disabilities (n = 3) due to progressive multifocal leukoencephalopathy, toxoplasmic encephalitis, and cryptococcal meningitis occurred between 2 to 25 weeks after the initiation of cART. All patients demonstrated a robust increase in blood CD4⁺ T-cell count in response to cART. A brain biopsy in one patient revealed inflammation and necrosis together with CD68⁺ macrophage and CD8⁺ T-cell infiltrates, which were also CD40 and CD154 immunoreactive. Two patients received corticosteroids as treatment for NeuroIRIS with an overall survival of 86%, while 14% exhibited fixed neurologic disabilities.

Conclusions: Immune reconstitution inflammatory syndrome in the nervous system (NeuroIRIS) remains an uncommon complication of combination antiretroviral therapy (cART) but with a potentially poor outcome. Initiation of cART in very immunosuppressed patients requires close monitoring to manage NeuroIRIS in an expedient manner.

Abbreviations: AFB = acid fast bacilli; cART = combination antiretroviral therapy; IRIS = immune reconstitution inflammatory syndrome; IVDU = IV drug use; MSM = men who have sex with men; N/A = not available; NAC = Northern Alberta Clinic; NeuroIRIS = neurologic immune reconstitution inflammatory syndrome; PML = progressive multifocal leukoencephalopathy; SAC = Southern Alberta Clinic; VL = viral load; WBC = white blood cells.

Supplemental data at www.neurology.org.

C.P. holds a Canada Research Chair in Neurological Infection and Immunity and is an Alberta Heritage Foundation for Medical Research Senior Scholar.

Disclosure: The authors report no disclosures.

Received July 23, 2008. Accepted in final form December 3, 2008.

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				Neurological Immune Reconstitution Inflammatory Syndrome in HIV Journal Watch Neurology, June 9, 2009; 2009(609): 2 - 2. [Full Text]

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