One of the possible causes of persistent inflammation of the brain parenchyma in the age of antiretrovirals is residual HIV replication, despite effective viral suppression in the bloodstream with Antiretroviral treatment (ART). The central nervous system (CNS) is infected early during primary HIV infection and is one of the reservoirs of this virus during chronic infection. Inadequate penetration of certain ART into the CNS could promote some degree of intrathecal HIV replication.We describe the case of an HIV-infected patient compliant to ART with an undetectable viral load in the blood but present in the cerebrospinal fluid (CSF). The patient presented with subacute rhombencephalitis due to HIV which was fatal to him.An HIV-infected and treated patient, well controlled on ART, with new neurological disorders, should be promptly investigated by brain MRI and CSF analysis for exhaustive detection of viruses including that of HIV itself.