Neurological complications of HIV infection

Abstract

The fact that HIV infection directly impacts the central nervous system (CNS) has been recognized since very early in the global HIV epidemic. The emergence of widespread antiretroviral therapy (ART) use has altered the clinical character of neurologic disease observed in HIV, led to new challenges related to optimization of CNS treatment, and raised a host of questions related to the role of the CNS as a potential barrier to HIV eradication and cure. This presentation will review key issues in this landscape of clinical and scientific issues facing people living with HIV, providers, and investigators in the current era. Potential mechanisms of HIV-related CNS dysfunction observed in patients treated with ART include persistent CNS infection, ongoing immune activation, effect of comorbidities including vascular disease, aging, antiretroviral drug exposure in the CNS associated with either toxicity or inadequate tissue distribution, and neurologic injury accrued prior to initiation of antiretroviral treatment. Related to issues of persistent clinical CNS abnormality in the face of ART, novel research questions are raised by efforts to successfully ‘cure’ HIV: whether the CNS may provide a reservoir for infection which may be a significant impediment to efforts to eradicate HIV. The pathobiology of this putative reservoir is under active investigation, including studies on the timing of establishment of CNS infection, the potential cells and tissues harboring HIV in the CNS, evidence of independent evolution of HIV in the CNS, and the possibility of autonomous CNS sources of HIV replication in the setting of suppressive therapy.