Growth and Neurotrophic Factors for HIV-Associated Neurocognitive Disorders

The advent of combination antiretroviral therapy (cART) has achieved remarkable success in controlling the replication of the human immunodeficiency virus (HIV). This success has resulted in reduced morbidity and increased life expectancy for individuals living with the virus. However, paradoxically, as patients have extended lifespans, there has been a concerning increase in the prevalence of HIV-associated cognitive impairments. This rise can be attributed to the adverse effects of drug toxicity and the limited ability of these drugs to penetrate the central nervous system (CNS). Moreover, the presence of HIV proteins, which remain unaffected by antiretrovirals, contributes to neuroinflammation. Consequently, many individuals effectively managed by cART experience various forms of HIV-associated neurocognitive disorders (HAND). The mechanisms underlying these disorders encompass deficits in calcium flux, excitotoxicity, cell signaling, oxidative stress, and autophagy. Furthermore, disruptions in the processing and functionality of neurotrophic factors, including fibroblast growth factors (FGFs), brain-derived growth factor (BDNF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and glial cell-derived neurotrophic factor (GDNF), have been implicated in the disruption of neuronal function. Notably, these factors have demonstrated their capacity to interfere with the fundamental process of apoptotic cell death, a key feature of HAND and other neurodegenerative diseases. Additionally, neurotrophic factors can potentially promote neuronal differentiation, neurogenesis, and angiogenesis thereby facilitating neuronal repair. There is a conspicuous absence of effective adjunctive treatments for these diseases. Consequently, identifying novel neuroprotective compounds for addressing such conditions is paramount in this field. This chapter delves into the beneficial roles of various neurotrophic factors, including FGF, BDNF, IGF, PDGF, and GDNF, within the context of potential HIV therapies.