Background: HIV-associated CD8 encephalitis (CDE) is a severe inflammatory disorder characterized by infiltration of the brain by CD8+ T-lymphocytes in HIV positive patients, often when the virus is well-controlled by anti-retroviral therapy (ART). Hallmark clinical features include headache, confusion and progressive cognitive decline. Most patients who receive prompt corticosteroid therapy evolve favorably, though if left untreated, CDE can lead to coma and even death. The therapeutic impact of altering the ART regimen while giving corticosteroids remains unclear. Methods: Patient chart, functional measures, and laboratory findings were reviewed for the length of the patient’s two hospitalisations for CDE in 2019 and 2021. Results: Here we present a case of an HIV positive 43-year-old male who presented with headache, confusion and memory issues both in 2019 and 2021. Imaging and lumbar puncture guided the diagnosis of CDE in 2019, while careful patient history on the patient’s second hospitalisation confirmed the diagnosis of HIV encephalitis due to medication non-compliance in 2021. Conclusions: This case adds to the current state of knowledge regarding the clinical presentation of CD8 encephalitis, while highlighting both similarities and differences with other CNS pathology seen in the context of HIV.