HIV Encephalitis in the Antiretroviral Era: Pathophysiology, Clinical Recognition, and Management

Human immunodeficiency virus (HIV) encephalitis represents a distinct neuroinflammatory condition resulting from direct and indirect effects of HIV within the central nervous system (CNS). Despite the widespread availability of combination antiretroviral therapy (ART), which has dramatically reduced the incidence of severe HIV-associated dementia, milder forms of neurocognitive impairment persist in nearly half of all HIV-infected individuals. This condition arises from complex pathophysiological mechanisms, including viral seeding of the CNS by infected monocytes, compartmentalized viral replication, and sustained release of neurotoxic cytokines from activated microglia and macrophages, rather than from direct neuronal infection. Clinically, HIV encephalitis typically presents with subcortical deficits—psychomotor slowing, executive dysfunction, and memory impairment—in a waxing and waning pattern distinct from the progressive cortical deterioration seen in Alzheimer disease. Diagnosis relies on comprehensive neuropsychological assessment, exclusion of opportunistic infections and neoplasms via cerebrospinal fluid analysis and neuroimaging, and recognition of characteristic magnetic resonance findings including cerebral atrophy and symmetric subcortical white matter hyperintensities. Effective management is founded upon prompt initiation of ART regimens with high CNS penetration effectiveness, with integrase strand transfer inhibitors such as dolutegravir representing preferred agents. The prognosis has been transformed from uniformly fatal within one year to a chronic, manageable condition, though poor adherence, advanced age, and baseline cognitive deficits predict poorer outcomes. An interprofessional team approach—integrating infectious disease specialists, neurologists, pharmacists, nurses, and mental health professionals—remains the cornerstone of comprehensive care, optimizing adherence, monitoring for complications such as CNS viral escape, and ultimately preserving quality of life for patients living with HIV encephalitis.