Abstract
Progressive multifocal leukoencephalopathy (PML) is a rare but often fatal demyelinating disease of the central nervous system, caused by the reactivation of the John Cunningham virus (JCV). It predominantly affects individuals with compromised immune systems, especially those living with AIDS. Immune Reconstitution Inflammatory Syndrome (IRIS) is a paradoxical event that can occur in patients receiving antiretroviral therapy (ART), where the immune system's recovery triggers a damaging inflammatory response. We present the case of a 39-year-old female patient with a history of AIDS and PML who was recently restarted on ART and presented with worsening left-sided weakness. She was managed for paradoxical PML and IRIS, and received steroids along with ART, with significant improvement.