Editorial: Advances in Understanding NeuroHIV Associated Changes in Neuroimmune Communication in the Combined Anti-retroviral Therapy (cART) Era

In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction.

The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages, as well as choroid plexus and meningeal macrophages, dendritic cells, and granulocytes. These myeloid populations enjoy an intimate relationship with the CNS, where they play an essential role in both health and disease. Although the importance of these cells is clearly recognized, their exact function in the CNS continues to be explored. Here, we review the subsets of myeloid cells that inhabit the parenchyma, meninges, and choroid plexus and discuss their roles in CNS homeostasis. We also discuss the role of these cells in various neurological pathologies, such as autoimmunity, mechanical injury, neurodegeneration, and infection. We highlight the neuroprotective nature of certain myeloid cells by emphasizing their therapeutic potential for the treatment of neurological conditions.