Progressive multifocal leukoencephalopathy (PML) usually affects immunocompromised people, such as those with advanced HIV or a haematological malignancy. A minority of initial PML diagnoses are in people who are minimally or mildly immunosuppressed (Berger et al. 1998; Gheuens et al. 2010). Management is to restore immune function where possible, and this can result in remission of the PML. The two cases we describe had initial remission of PML, with subsequent development of symptoms and investigation findings consistent with recurrent PML despite interval maintenance of minimal immunosuppression and HIV suppression. This has not previously been described.