Growth and neurotrophic factors in HIV-associated neurocognitive disorders

The advent of combination antiretroviral therapy (cART) has successfully controlled replication of the human immunodeficiency virus (HIV) leading to reduced morbidity and increased longevity of infected people. Paradoxically however, as patients live longer lives, the prevalence of HIV-associated cognitive impairments has risen due to drug toxicity and its limited cART central nervous system (CNS) penetrance. Additionally, the presence of HIV proteins, which are not impacted by antiretrovirals, are a source of neuroinflammation. As a result, almost 50 % of infected individuals on effective cART exhibit various forms of HIV-associated neurocognitive disorders (HAND) whose mechanism(s) include deficits in calcium flux, excitotoxicity, cell signaling, oxidative stress and autophagy. Additionally, defects in the processing and functioning of neurotrophic factors such as fibroblast growth factors, brain-derived growth factor, insulin-like growth factor, platelet-derived growth factor, and glial cell derived neurotrophic factor have also been implicated in disruption of neuronal function. Importantly, these factors have been shown to interfere with the fundamental mechanism of apoptotic cell death, the underlying feature of HAND and other neurodegenerative diseases. Additionally, neurotrophic factors are also capable of promoting neuronal differentiation, neurogenesis and angiogenesis, thereby facilitating repair. Currently, there are no effective adjunctive treatments for disease. Thus, identifying novel neuroprotective molecules for treating such diseases is highly warranted in this field. This chapter discusses the beneficial roles of those neurotrophic and growth factors in the context of potential HIV therapies.