A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS

Abstract

Cidofovir did not improve neurological examination scores at week 8. However, such scores were significantly better in subjects who entered with suppressed plasma HIV-1-RNA levels, which could be the result of control of HIV-1 infection itself or cidofovir.

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

“…Numerous therapies have been anecdotally reported to be successful, but PML progression may rarely be stopped by reducing or eliminating immunosuppression (37). Agents that have failed to alter the course of PML include interferon-␣, cidofovir, topotecan, and cytarabine (102)(103)(104)(105). Several rheumatic disease patients have survived after withdrawal of immunosuppressive therapy and initiation of cidofovir, interferon, or cytarabine treatment, but in no case was there a clear therapeutic response.…”

Progressive Multifocal Leukoencephalopathy After Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia

“…Immunomodulatory agents such as interleukin-2 and interferon-alpha, and antivirals such as cytarabine and cidofovir have shown efficacy in isolated cases but failed to show benefit in larger studies. [38][39][40] Because JCV entry into human glial cells may be mediated by the serotonergic 5-HT 2A receptor, interest has been shown in using 5-HT 2A receptor antagonists, such a mefloquine and mirtazapine, to treat PML. 41 However, a phase I/II clinical trial (ClinicalTrials.gov identifier: NCT00746941) that studied the effects of mefloquine in patients with PML was terminated early because it failed to reduce the titer of JCV in the CSF after treatment, a finding consistent with the outcome of the patient described in Case 1.…”

Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls

“…A subsequent trial tested the topoisomerase inhibitor topotecan, which proved toxic with minimal activity resulting in discontinuation of the trial after accrual of only 12 patients [50]. Subsequently, cidofovir therapy was tested in a phase 1-2 open-label trial with 24 patients, but did not improve the survival as seen with the use of cART [51]. Cidofovir outcomes were combined with several observational cohorts in a careful meta-analysis that confirmed no efficacy on mortality or morbidity using cidofovir [52].…”