Immune reconstitution inflammatory syndrome in a patient with progressive multifocal leukoencephalopathy

Abstract

SUMMARYProgressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection of the central nervous system. A 52-year-old man with HIV infection, recently started on antiretroviral therapy, presented with symptoms of mental cloudiness, blurry vision and ataxia. MRI of the brain showed nodular perivascular space enhancement with surrounding vasogenic oedema and midline shift. A lumbar puncture revealed noninflammatory cerebrospinal fluid and was positive for JC virus. As the patient developed worsening symptoms in the setting of initiation of antiretroviral therapy with immune recovery, a diagnosis of JC virus-associated immune reconstitution inflammatory syndrome (IRIS) was made. With recent literature on the use of CCR5 antagonist maraviroc in PML, our patient was started on maraviroc and noted to have improvement in PML IRIS. This is the first case of an HIV-positive patient successfully treated for PML IRIS with maraviroc, as verified by our literature review; also, our case has clinical implications in improving outcome in PML IRIS. BACKGROUND

Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review

“…Building on these observations, it was suggested that CCR5 might be implicated in the pathogenesis of PML-IRIS, hence warranting further studies. The single patient in our review who received maraviroc and the very few contradictory published case reports prevent us from drawing conclusions on the potential immunomodulatory benefits of maraviroc in inflammatory PML settings ( 29 , 38 , 58 , 60 ). Worthy of note, the double-blinded randomized placebo-controlled CADIRIS trial showed that the addition of maraviroc to cART did not reduce the risk of IRIS in 276 patients with advanced HIV infection ( 62 ).…”

Not a Disease of the Past: A Case Series of Progressive Multifocal Leukoencephalopathy in the Established Antiretroviral Era

“…9,34,35 Several small reports and case series have supported this conjecture. 12 Although the CADIRIS study, a large randomized controlled trial evaluating the use of maraviroc for the prevention of development of any IRIS-related disease, ultimately found no reduction in incident IRIS with the addition of maraviroc, there are several potential limitations to applying this study to the PML population as there were no instances of PML identified in the CADIRIS study. 13 Therefore, the findings of the CADIRIS study are not applicable to PML-IRIS.…”

“…9,10 As a result, maraviroc is currently being used anecdotally for the treatment of PML-IRIS in both the multiple sclerosis and HIV populations, with mixed results. [11][12][13] Because the initial studies describing immune cell trafficking in PML-IRIS were performed in HIV-negative patients, there is some concern that these results may not apply to PLWH and PML-IRIS. 14 Therefore, guidelines for the management of PML-IRIS do not make definitive recommendations regarding the use of maraviroc, citing a lack of quality evidence to support its general use.…”

Prevention and therapy of JC polyomavirus-mediated progressive multifocal leukoencephalopathy – a realistic possibility?

“…Alternatively, the C-C motif chemokine receptor (CCR5) antagonist maraviroc approved for the treatment of HIV infection, has been discussed to be useful in preventing overshooting IRIS [88][89][90]. Since maraviroc was not helpful in other PML cases [91], its therapeutic role for PML-IRIS prevention or treatment has to be defined in larger trials.…”