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HIV cure strategists: ignore the central nervous system at your patients' peril.

Early in the AIDS epidemic, numerous investigators determined that central nervous system (CNS) disorders including dementia were common among persons infected with HIV. Moreover, it has been established that infected persons without clearly identified dementia can have mild HIV associated neurological disorders [1]. HIV can be identified within cerebrospinal fluid (CSF) of almost all HIV-infected persons not receiving antiretroviral therapy (ART) and post-mortem brain tissues have readily detectable viral expression primarily within resident microglial cells and macrophages [2,3]. Furthermore, in patients with undetectable viral load in both plasma and CSF, HIV DNA was detectable in all subjects in brain autopsy tissue [4]. Further, experimental animal models in which CD4þ T cells are depleted or absent emphasize the importance of the macrophage reservoir [5,6]. Thus, it is somewhat surprising that the CNS as an important reservoir in persons receiving treatment remains hotly debated.