HIV infected people are living longer due to the success of combined antiretroviral therapy (cART). However,
greater than 40-70% of HIV infected individuals develop HIV associated neurocognitive disorders (HAND) that continues
to be a major public health issue. While cART reduces peripheral virus, it does not limit the low level, chronic
neuroinflammation that is ongoing during the neuropathogenesis of HIV. Monocyte transmigration across the blood brain
barrier (BBB), specifically that of the mature CD14+CD16+ population that is highly susceptible to HIV infection, is
critical to the establishment of HAND as these cells bring virus into the brain and mediate the neuroinflammation that
persists, even if at low levels, despite antiretroviral therapy. CD14+CD16+ monocytes preferentially migrate into the CNS
early during peripheral HIV infection in response to chemotactic signals, including those from CCL2 and CXCL12. Once
within the brain, monocytes differentiate into macrophages and elaborate inflammatory mediators.
Monocytes/macrophages constitute a viral reservoir within the CNS and these latently infected cells may perpetuate the
neuropathogenesis of HIV. This review will discuss mechanisms that mediate transmigration of CD14+CD16+ monocytes
across the BBB in the context of HIV infection, the contribution of these cells to the neuropathogenesis of HIV, and
potential monocyte/macrophage biomarkers to identify HAND and monitor its progression.