Maraviroc and JC Virus-Associated Immune Reconstitution Inflammatory Syndrome

New England Journal of Medicine (Impact Factor: 55.87). 01/2014; 370(5):486-8. DOI: 10.1056/NEJMc1304828
Source: PubMed


The immune reconstitution inflammatory syndrome can be a serious complication of immune reversal in the treatment of progressive multifocal leukoencephalopathy. A new potential treatment for IRIS is described in this letter.To the Editor: The immune reconstitution inflammatory syndrome (IRIS) can be a serious complication in immunocompromised patients in whom progressive multifocal leukoencephalopathy (PML) has developed. IRIS occurs in such patients when their immunocompromised state reverses.(1) Although restored immune surveillance is vital for clearing the JC virus that causes PML, improved management strategies for IRIS are needed because of its potential for considerable complications and death. The common, though unproven, use of glucocorticoids to treat IRIS may limit JC viral clearance.(2) Because of the indirect implication of chemokine receptor 5-positive (CCR5+) T cells in IRIS pathophysiology,(3) we used the small-molecule CCR5 ...

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Available from: Marie-Noelle Boivin, Dec 01, 2014
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    • "CCR5 is apparently involved in targeting inflammatory responses, and in animal models, blocking CCR5 has inhibited encephalitic responses in animal models and in graft versus host disease in humans (Glass et al. 2004; Reshef et al. 2012). Several case reports including both HIV-and natalizumab-associated PML support the possibility that maraviroc therapy may blunt IRIS in the setting of PML (Martin-Blondel et al. 2009; Giacomini et al. 2014). It appears that a potentially useful randomized trial testing optimal immune reconstitution with or without maraviroc would provide scientifically useful observations. "
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    ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is caused by the JC virus in the setting of chronic immune deficiency. Developing therapy has been challenged by the rarity of the disease as well as the complexity of patients in whom it develops. Several small trials directed at presumptive antiviral therapies have failed to show convincing clinical efficacy. However, the prognosis of PML has evolved from an almost uniformly fatal encephalitis to a disease where a majority of patients survive. This improvement in outlook has been driven by effective immune reconstitution strategies for the underlying disease, most prominently the improved therapy for human immunodeficiency virus and ability to reverse the effects of natalizumab. While a rapid acting and effective antiviral therapy remains a sought for goal, optimal immune reconstitution to control JC virus without causing brain-damaging immune reconstitution inflammatory syndrome (IRIS) currently is the most practical approach to treat PML.
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    ABSTRACT: An immune reconstitution disorder occurs in up to 40 % of severely immunodeficient HIV patients who commence antiretroviral therapy (ART), with an immune reconstitution inflammatory syndrome (IRIS) being encountered most commonly. Differences in the immunopathogenesis of an IRIS associated with different types of pathogen have become apparent but common features have also been defined. These include severe immunodeficiency prior to commencing ART associated with a high pathogen load and 'compensatory' immune responses, particularly innate immune responses, which inadequately control the pathogen and increase the risk of immunopathology as the immune system recovers on ART. Prevention of an IRIS may be achieved by optimising therapy for opportunistic infections before ART is commenced, delaying ART or using immunomodulatory therapy to prevent or suppress the immune response that causes the immunopathology. However, further clinical studies are required to examine these options in a systematic manner for the various types of IRIS.
    Current HIV/AIDS Reports 06/2014; 11(3). DOI:10.1007/s11904-014-0213-0 · 3.80 Impact Factor
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