The effect of substance misuse on HIV persistence in the CNS

Abstract

Substance use and HIV infection are major social, medical, and scientific challenges that have a large degree of overlap in the populations that they affect. An abundance of studies show that substance use alters the development of neuropathology associated with chronic HIV infection. These include findings that support a role for substances of misuse in affecting the long-lived population of HIV-infected cells in the central nervous system (CNS). These cells are primarily myeloid populations, such as microglia and perivascular macrophages, and are thought to comprise a viral reservoir in the CNS. This reservoir is a potential source of viral rebound during cessation of therapy and is considered a major driver of neuropathogenesis. The primarily myeloid composition of the CNS reservoir is distinct from the cell types comprising peripheral reservoirs, making it likely to be established, maintained, and acted upon by different mechanisms and then those described for the periphery. In this chapter, we review the sociological effects of substance use that could influence the establishment, size and growth of the CNS reservoir, the immunologic considerations that affect how cells of reservoir may induce neuropathogenesis, and what is known regarding the molecular and epigenetic mechanisms that alter viral transcription and control replication in the cells comprising the CNS reservoir.