New Potential Axes of HIV Neuropathogenesis With Relevance to Biomarkers and Treatment

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) affect approximately half of people living with HIV despite viral suppression with antiretroviral therapies and represent a major cause of morbidity. HAND affects activities of daily living including driving, using the Internet and, importantly, maintaining drug adherence. Whilst viral suppression with antiretroviral therapies (ART) has reduced the incidence of severe dementia, mild neurocognitive impairments continue to remain prevalent. The neuropathogenesis of HAND in the context of viral suppression remains ill-defined, but underlying neuroinflammation is likely central and driven by a combination of chronic intermittent low-level replication of whole virus or viral components, latent HIV infection, peripheral inflammation possibly from a disturbed gut microbiome or chronic cellular dysfunction in the central nervous system. HAND is optimally diagnosed by clinical assessment with imaging and neuropsychological testing, which can be difficult to perform in resource-limited settings. Thus, the identification of biomarkers of disease is a key focus of the field. In this chapter, recent advances in the pathogenesis of HAND and biomarkers that may aid its diagnosis and treatment will be discussed.