We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment.