Journal of NeuroVirology

, Volume 19, Issue 4, pp 351-358

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes

  • David B. CliffordAffiliated withDepartment of Neurology, Washington University in St. Louis Email author 
  • , Avindra NathAffiliated withSection of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health
  • , Paola CinqueAffiliated withDepartment of Infectious Diseases, San Raffaele Scientific Institute
  • , Bruce J. BrewAffiliated withDepartments of Neurology and HIV Medicine, St Vincent’s Hospital and University of New South WalesDepartment of Neurology, Level 4, Xavier Building, St. Vincent’s Hospital
  • , Robert ZivadinovAffiliated withDepartment of Neurology, Buffalo Neuroimaging Analysis CenterJacobs Neurological Institute
  • , Leonid GorelikAffiliated withDepartment of Research, Biogen Idec Inc.Biogen Idec Inc.
  • , Zhenming ZhaoAffiliated withPharmaceutical Product Development, LLC
  • , Petra DudaAffiliated withDepartment of Medical Research, Biogen Idec Inc.Biogen Idec Inc.


Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.


Mefloquine Leukoencephalopathy Progressive multifocal JC virus Magnetic resonance imaging