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Do CCR5 antagonists improve the overall survival of patients with AIDS-related progressive multifocal leucoencephalopathy?
  1. Edouard Januel1,
  2. Guillaume Martin-Blondel2,3,
  3. Cédric Lamirel4,
  4. Hervé Picard1,
  5. Gilles Pialoux5,
  6. Christine Katlama6,
  7. Isabelle Cochereau4,
  8. François-Xavier Lescure7,
  9. Antoine Moulignier8
  1. 1 Unité de Recherche Clinique, Fondation Adolphe de Rothschild, Paris, France
  2. 2 Service des Maladies Infectieuses et Tropicales, CHU Toulouse, Toulouse, France
  3. 3 INSERM UMR1043–CNRS UMR5282, Université Toulouse III, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France
  4. 4 Département d’Ophtalmologie, Fondation Adolphe de Rothschild, Paris, France
  5. 5 Service des Maladies Infectieuses et Tropicales, Assistance Publique−Hôpitaux de Paris, Hôpital Tenon‒Université Paris 6, Paris, France
  6. 6 Service des Maladies Infectieuses et Tropicales, Assistance Publique−Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière‒Université Paris, Paris, France
  7. 7 Service des Maladies Infectieuses et Tropicales, Assistance Publique−Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, and IAME, UMR 1137, Sorbonne Paris Cité, Université Paris 7, Paris, France
  8. 8 Service de Neurologie, Fondation Adolphe de Rothschild, Paris, France
  1. Correspondence to Dr Antoine Moulignier, Service de Neurologie, Fondation Adolphe de Rothschild, Paris 75019, France; amoulignier{at}fo-rothschild.fr

https://doi.org/10.1136/jnnp-2017-317203

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    Introduction

    Progressive multifocal leucoencephalopathy (PML), a devastating demyelinating disease caused by John Cunningham virus (JCV) reactivation, affects patients with severe immune deficiencies.1 Despite having tested numerous molecules over the last 25 years, their benefits have often been overstated based on isolated case reports or small series.1 Because those therapies offered patients with PML some, although limited, hope, the desire to try an inaccurately tested but potentially lifesaving treatment surpasses rigorous clinical trial evaluation before widespread use. Notably, cidofovir’s alleged promise, based on case reports, largely evaporated when prospective cohort studies demonstrated that it had no influence on AIDS-related PML (AR-PML) overall survival (OS) or residual disability.2 That story might be repeating itself with maraviroc (MVC) use, also based on only a few favourable case reports.3

    Restoring JCV-specific immune responses is the most effective way to improve survival of patients with PML.1 Immune recovery is not always beneficial and a subset of patients with PML may worsen due to immune reconstitution inflammatory syndrome (PML-IRIS), mediated by CD8+ T cells strongly expressing CC chemokine receptor-5 (CCR5). MVC is a non-competitive CCR5 antagonist approved in the HIV armamentarium. Histological findings and some case reports inferred that MVC might work as a mediating double-edged sword by enhancing CD4+ T-cell reconstitution and its potential immunomodulatory properties to improve AR-PML and AR-PML-IRIS survival in various conditions (idiopathic CD4+ T-cell lymphocytopaenia, sarcoidosis and natalizumab-treated patients with multiple sclerosis).4 But, MVC had no beneficial effect on OS of patients with PML in one-third of reports (online supplementary …

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    Footnotes

    • Contributors EJ: performed medical chart research and data acquisition, analysed the data and contributed to the writing of the manuscript. GM-B: contributed to study concept, acquisition and interpretation of the data, and writing of the manuscript. CL and F-XL: contributed to interpretation of the data and writing of the manuscript. HP: performed data analysis and interpretation, and critical revision of the manuscript. GP, CK and IC: contributed to interpretation of the data and critical revision of the manuscript. AM: was responsible for study concept, overall supervision of interpretation of the data and writing of the manuscript.

    • Funding GM-B has received lecture fees from Abbvie,Pfizer and ViiV Healthcare France, and travel and accommodations funding from Eumedica France. CL reports lecture fees and travel and accommodations funding from Allergan and Thea, and lecture fees from Alcon. GP reports grants from Gilead and BMS, lecture fees from Abbvie Viiv Healthcare, GSK, Janssen, MSD, and Nephrotek. CK reports grants and lecture fees from Merck-Sharp-Dome, Bristol-Myers-Squibb, Viiv Healthcare and Gilead Sciences, and grants from Janssen Pharmaceuticals. F-XL reports lecture fees from MSD, GILEAD and Biomerieux, travel and accommodations funding from Genmark and for meeting travel from Eumedica and Pfizer. AM reports lecture fees and travel and accommodations funding from Biogen Idec, Novartis and MSD, and travel and accommodations funding from Teva and Merck-Serono.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval The Rothschild Foundation’s Institutional Review Board.

    • Provenance and peer review Not commissioned; externally peer reviewed.