The purpose of this review is to examine the literature concerning immune reconstitution disease associated with the central nervous system infections.

Immune reconstitution disease is an adverse consequence of antiretroviral therapy, characterized by an aberrant immune response and presenting with new or worsening clinical symptoms and signs after initiation of antiretroviral therapy. Immune reconstitution disease may be associated with a broad spectrum of infectious pathogens, and has been described in the context of central nervous system infections, including progressive multifocal leucoencephalopathy, human herpesvirus infections, cryptococcal meningitis and tuberculous meningitis. Central nervous system immune reconstitution disease is a challenging condition as the clinical features are nonspecific, there is no agreed case definition, the immunopathogenesis is poorly understood, and the optimal treatment strategy is unknown. Central nervous system immune reconstitution disease appears to be associated with worse outcome than extracranial immune reconstitution disease.

Reports of central nervous system immune reconstitution disease are increasing and this trend is likely to continue as access to antiretroviral therapy improves in resource-limited settings in which many central nervous system infections are endemic. Considerable challenges remain in the prevention, diagnosis and management of these conditions.