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.