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Published online before print January 7, 2009, doi:10.1212/01.wnl.0000343510.08643.74)
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 Volume 72, Number 17, April 28, 2009
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NEUROLOGY 2009;72:1458-1464
© 2009 American Academy of Neurology

PML-IRIS in patients with HIV infection

Clinical manifestations and treatment with steroids

K. Tan, BM, BS, MRCP (UK), R. Roda, MD, PhD, L. Ostrow, MD, PhD, J. McArthur, MBBS, MPH and A. Nath, MD

From the Department of Neurology, Johns Hopkins University, Baltimore, MD.

Address correspondence and reprint requests to Dr. Avindra Nath, Department of Neurology, 509 Pathology, 600 N. Wolfe St., Baltimore, MD 21287 anath1{at}jhmi.edu

Background: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection that develops in immunosuppressed patients with HIV infection. Paradoxically, some of these patients may develop PML during combined antiretroviral therapy in the setting of immune reconstitution. We describe the types of PML in relation to immune reconstitution inflammatory syndrome (IRIS) and the effects of steroid use in these patients.

Methods: We performed a retrospective review of the literature (1998 to 2007) and of all HIV-infected patients diagnosed with PML-IRIS at Johns Hopkins Hospital (2004 to 2007). We recorded information on clinical features, microbiologic and virological analysis, neuroimaging, pathology, treatment, and outcome.

Results: Of 54 patients with PML-IRIS, 36 developed PML and IRIS simultaneously (PML-s-IRIS) and 18 had worsening of preexisting PML (PML-d-IRIS) after the initiation of combined antiretroviral therapy. PML-IRIS developed between 1 week and 26 months after initiation of antiretroviral therapy. PML-d-IRIS patients developed IRIS earlier, had higher lesion loads on MRI of the brain, had shorter durations of survival, and had higher mortality rate compared to PML-s-IRIS patients. Twelve patients received treatment with steroids, of which five died and seven showed good neurologic recovery. Patients who survived had received steroids early after IRIS diagnosis for longer durations and had contrast enhancement on IRIS neuroimaging.

Conclusions: Immune reconstitution following initiation of combined antiretroviral therapy may lead to activation of an inflammatory response to detectable or latent JC virus infection. Early and prolonged treatment with steroids may be useful in these patients but requires further investigation.

Abbreviations: FLAIR = fluid-attenuated inversion recovery; HAART = highly active antiretroviral therapy; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; JHH = Johns Hopkins Hospital; PML = progressive multifocal leukoencephalopathy; PML-d-IRIS = worsening of preexisting PML; PML-s-IRIS = PML and IRIS simultaneously.

Supplemental data at www.neurology.org

Editorial, page 1454

e-Pub ahead of print on January 7, 2009, at www.neurology.org.

Disclosure: The authors report no disclosures.

Received July 3, 2008. Accepted in final form November 12, 2008.


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