Multiple CNS infections can coexist in advanced AIDS, but are most commonly reported in autopsy case studies. We describe the case of an HIV+ individual, who was first diagnosed with CNS toxoplasmosis, confirmed by brain biopsy. After initiation of combined anti-retroviral therapy (cART) and successful treatment of CNS toxoplasmosis, he developed worsening neurological symptoms and was subsequently diagnosed with progressive multifocal leukoencephalopathy. Retrospective analysis of the MRI scans indicated that PML was already present early on but was interpreted as edema associated with CNS toxoplasmosis. Clinicians should be aware that multiple pathologies may coexist in the brain of immunosuppressed individuals and that PML may develop and worsen despite the use of cART.