PML-IRIS in patients with HIV infection: clinical manifestations and treatment with steroids

Abstract

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.

Figure 1 Axial FLAIR and contrast-enhanced brain MRIs in two patients Axial fluid-attenuated inversion recovery (FLAIR) (A, B) and contrast-enhanced (C) brain MRI showing abnormal hyperintensity in the right motor strip (arrow in A). Seven weeks later, after completion of steroid treatment, there is enlargement of the contrast-enhanced lesion (B; arrowhead in C) despite clinical improvement. (D) Another patient with HIV infection and progressive multifocal leukoencephalopathy who had extensive patchy white matter involvement on an axial FLAIR image and (E) prominent contrast enhancement.

Figure 2 Time to onset of PML-s-IRIS and PML-d-IRIS after initiation of combined antiretroviral therapy IRIS = immune reconstitution inflammatory syndrome; PML = progressive multifocal leukoencephalopathy; PML-d-IRIS = worsening of preexisting PML; PML-s-IRIS = PML and IRIS simultaneously.