Neurocognitive decline associated with HIV infection remains prevalent even in the antiretroviral therapy (ART) era, albeit usually in less severe forms. The differential diagnosis of cognitive impairment in this population is quite broad, including infectious causes such as CNS opportunistic infections, causes directly related to HIV such as HIV-associated neurocognitive disorders and causes entirely unrelated to HIV infection such as primary dementia syndromes. In this case, a 47-year old man with HIV and on ART with an undetectable plasma viral load presented with rapidly progressive dementia to a clinic in Zambia. He had been functioning independently and fully employed prior to symptom onset but had to stop working within two months of symptom onset due to the severity and rapidity of his cognitive decline. Initial workup led to an empiric diagnosis and initiation of an empiric treatment regimen which was ultimately ineffective. This prompted re-evaluation, addition workup and, ultimately, discovering the correct diagnosis. This case highlights the stepwise approach to developing a diagnosis in a resource-limited setting where there exists a high burden of HIV infection, including the necessity of empiric diagnoses of treatment plans when investigations are limited and the importance of reconsidering these diagnoses in the face of additional clinical information. In addition, it highlights both infectious and non-infectious causes of cognitive decline in people with HIV.