Failure of antiviral therapy with brincidofovir in non-HIV progressive multifocal leukoencephalopathy
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LETTER TO THE EDITOR
Failure of antiviral therapy with brincidofovir in non‑HIV progressive multifocal leukoencephalopathy Jean‑Philippe Talarmin1 · Schéhérazade Rezig2 · Adissa Tran‑Minoui3 · Christian Berthou4 · Jean‑Richard Eveillard4 Received: 26 December 2019 / Accepted: 9 February 2020 © Belgian Neurological Society 2020
Keywords Progressive multifocal leukoencephalopathy · Brincidofovir · CMX001 · JC virus Dear Editor, Brincidofovir (formerly CMX001) is a lipid conjugate of cidofovir, with a broad-spectrum activity against dsDNA viruses [1]. Although it has mainly been used in adenovirus infections, brincidofovir has shown potent activity against polyomaviruses in in vitro models [2]. It also demonstrated suppression of JC virus replication in human brain-derived cells [2] and in human brain progenitor-derived astrocytes and COS-7 cells [3], with a favorable toxicity profile. Moreover, brincidofovir seems to have a higher in vitro potency (100–1000-fold greater) than cidofovir, and, unlike the latter, is orally available, penetrates into the central nervous system, and does not cause nephrotoxicity by accumulating in renal tubules [1]. Thus, Brincidofovir might be a therapeutic option for progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system due to the reactivation of JC virus in a context of severe immunodeficiency, for which no approved treatment is available. However, clinical data are scarce, and to the best of our knowledge only one case report has been published, in a patient diagnosed with PML complicating idiopathic CD4+ lymphocytopenia [4]. The patient presented with progressive neurological symptoms, and did not respond to the initial treatment with * Jean‑Philippe Talarmin jp.talarmin@ch‑cornouaille.fr 1
Department of Internal Medicine and Infectious Diseases, Centre Hospitalier de Cornouaille, Quimper, France
2
Department of Infectious Diseases, Centre Hospitalier Universitaire, Brest, France
3
Department of Virology, Centre Hospitalier Universitaire, Brest, France
4
Department of Hematology, Centre Hospitalier Universitaire, Brest, France
risperidone, cidofovir, and mefloquine. Cidofovir and mefloquine were discontinued, and brincidofovir was initiated, followed 3 weeks later by an investigational interleukin-7 to increase the CD4+ cell count. During the following weeks, neurological function stabilized, and the serum viral load decreased from 3456 to 100 copies/mL [4]. During the 38th meeting of the International Society for Heart and Lung Transplantation in 2018, a poster by Schneider and colleagues reported two more cases of patients treated with Brincidofovir, which have not been published yet [5]. The two patients were lung transplant recipients, and developed PML, respectively, 2.5 and 9.5 years post transplantation. A significant improvement was noted for both patients after initiation of Brincidofovir, before progression resumed and patients died. We report two cases of patients, who received brincidofovir on a compa
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