HIV is undoubtedly neurovirulent and neuropathogenic. The prevalence of HIV-associated neurocognitive disorder (HAND) remains high (estimated 30–50%) and persists despite plasma HIV RNA suppression with potent combination antiretroviral therapy. These cognitive dysfunctions range in severity, spanning from the milder deficits of asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) to more severe deficits in HIV-associated dementia (HAD). These cognitive deficits are not only widespread but impact everyday functioning, and increase morbidity and mortality with critical public health effects. To date, there are no clinically proven therapies for HAND for individuals already on stable, virologically suppressive anti-HIV regimens. Monocytes are thought to contribute to HAND pathogenesis by mediating HIV-neuroinvasion, which ultimately leads to HIV in the brain tissue, neuroinflammation and neuronal damage.
Productive HIV infection in the brain is found within the inflammatory infiltrate, which predominantly consists of macrophages. Although HIV is found in much lower frequency in brain tissues from patients on cART, we have successfully identified HIV-positive cells in cerebellum tissue that are surrounded by infiltrating macrophages using RNAscope, a novel next generation in situ hybridization technique.