Tenofovir in Progressive Multifocal Leukoencephalopathy

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the CNS caused by reactivation of the JC polyomavirus (JCV), typically in immunocompromised individuals. As no specific therapy against JCV exists, current management focuses on immune reconstitution. Recently, a potential therapeutic effect of tenofovir was reported. METHODS: We report 2 patients with PML who received tenofovir under a compassionate use protocol. Treatment was accompanied by MRI, clinical, and virologic monitoring. RESULTS: In both patients (serum and CSF), viral load was markedly reduced. In 1 patient, this was accompanied by temporary clinical stabilization and reduction in MRI lesion burden. The other patient further declined clinically, accompanied by progression of MRI lesion size and contrast enhancement. Dense lymphocytic infiltration on biopsy suggested predominant effects of alleviated immunosuppression rather than the direct antiviral drug effect. Both patients ultimately died of the disease. DISCUSSION: Despite virus reduction in both cases, sustained clinical improvement was not achieved. This suggests that viral load reduction alone is insufficient, and pathogenesis may be largely driven by the immune response to the infection. A combination of tenofovir with low-dose anti-inflammatory drugs may be a useful addition to PML therapy.