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J Neuroimmunol. 2010 Feb 26;219(1-2):100-4. doi: 10.1016/j.jneuroim.2009.11.013. Epub 2009 Dec 4.

Unmasking of PML by HAART: unusual clinical features and the role of IRIS.

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Owen Clinic, Antiviral Research Center, and HIV Neurobehavioral Research Center, University of California, San Diego, La Jolla, CA, United States.


For patients with HIV/AIDS, highly active antiretroviral therapy (HAART) is currently the only effective therapy for progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease caused by polyomavirus JC. Immune reconstitution inflammatory syndrome (IRIS) following initiation of HAART can cause paradoxical clinical deterioration in patients with established PML. Because the onset of PML follows soon after initiation of HAART in some cases (unmasking), we investigated the role IRIS plays in unmasked PML. We reviewed records of 20 PML cases seen from 1997-2006 at the UCSD HIV primary care clinic. Eight cases presented with PML symptoms within 6months of initiating HAART (referred to hereafter as unmasked PML), six patients were diagnosed with PML before initiating HAART, and six were diagnosed more than 6months after starting HAART. Patients with unmasked PML constituted 40% of our series, had relatively long survival, and commonly (50%) had lesions exclusively in the posterior fossa, a localization not previously reported with such a high prevalence. Only 3 of the 8 patients with unmasked PML had IRIS reactions as evidenced by contrast enhancement around lesions on MRI, suggesting that IRIS is not necessary for the pathogenesis of this syndrome.

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