Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review
Abstract
Incidence of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients
has declined in the combined antiretroviral therapy (cART) era although a growing
number of acquired immunodeficiency syndrome (AIDS)-related PML-immune reconstitution inflammatory syndromes (PML-IRIS) have been published during the same
period. Therapeutic management of PML-IRIS is not consensual and mainly relies
on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of
published PML-IRIS cases, to assess the benefit of corticosteroids in the management
of PML-IRIS, focusing on confirmed cases. We performed a literature review of the 46
confirmed cases of PML-IRIS cases occurring in HIV-infected patients from 1998 to
September 2016 (21 unmasking and 25 paradoxical PML-IRIS). AIDS-related PML-IRIS
patients were mostly men (sex ratio 4/1) with a median age of 40.5 years (range 12–66).
Median CD4 T cell count before cART and at PML-IRIS onset was 45/μl (0–301) and
101/μl (20–610), respectively. After cART initiation, PML-IRIS occurred within a median
timescale of 38 days (18–120). Clinical signs were motor deficits (69%), speech disorders (36%), cognitive disorders (33%), cerebellar ataxia (28%), and visual disturbances
(23%). Brain MRI revealed hyperintense areas on T2-weighted sequences and FLAIR
images (76%) and suggestive contrast enhancement (87%). PCR for John Cunningham
virus (JCV) in cerebrospinal fluid (CSF) was positive in only 84% of cases; however, when
performed, brain biopsy confirmed diagnosis of PML in 90% of cases and demonstrated
histological signs of IRIS in 95% of cases. Clinical worsening related to PML-IRIS and
leading to death was observed in 28% of cases. Corticosteroids were prescribed in 63%
of cases and maraviroc in one case. Statistical analysis failed to demonstrate significant benefit from steroid treatment, despite spectacular improvement in certain cases.
Diagnosis of PML-IRIS should be considered in HIV-infected patients with worsening
neurological symptoms after initiation or resumption of effective cART, independently
of CD4 cell count prior to cART. If PCR for JCV is negative in CSF, brain biopsy should
be discussed. Only large multicentric randomized trials could potentially demonstrate
the possible efficacy of corticosteroids and/or CCR5 antagonists in the management of
PML-IRIS.