This Research Topic will focus on our developing understanding of the role of neuroimmune communication in neurological disorders in people living with HIV (PLWH) during the era of anti-retroviral therapy ART.
HIV infection has been transformed from a terminal diagnosis to a chronic disease, greatly extending the lives of infected individuals with access to ART. However, this success has also led to new health challenges, including the development of long-term neurological dysfunction. Prior to ART, infected individuals showed rampant neuroinflammation and significant neuronal death associated with high rates of dementia, but with ART the neuropathology associated with HIV infection has become more complex and subtler.
However, even full suppression of viral replication with the use of cART with good CNS penetrance, minor neurocognitive dysfunction, depression, and other neuropsychiatric adverse events (NPAE) remain prevalent. This suggests that the etiology of these conditions is not solely derived from viral replication. Instead, data suggest that NeuroHIV stems from dysfunction in the neuroimmune cross-talk that regulates the interactions between neural circuits, support glia, and the HIV-infected cells in the brain. Moreover, recent evidence suggests that antiretroviral drugs, both alone and through their interaction with other therapeutics, may also contribute to changes in neuroimmune communication and neurological dysfunction. These problems are particularly acute for the aging HIV-infected population, as these individuals are often on long-term ART in combination with other therapeutics.
Proper CNS function is maintained by complex interactions between neurons, astrocytes, microglia, and CNS macrophages. Cytokines and neurotrophic factors produced by supporting cells are central to neuronal health and effective, bidirectional neuroimmune communication. These interactions facilitate synapse formation and dissolution, modulate neurotransmission, and provide neuronal protection. Dysregulation of these interactions can result from HIV- or ART-associated changes in immune cell functions such as chemotaxis, phagocytosis of extracellular aggregates and damaged neurons, production of cytokines or trophic factors, maintenance of CNS vasculature, or alterations in neurotransmitter uptake. These changes can lead to the development of neuroinflammation and neuronal dysfunction and degeneration, significantly impairing the activity of neuronal circuits and resulting in behavioral changes and cognitive deficits.
The aim of this Research Topic is to more precisely define the specific changes in neuroimmune communication that are occurring in ART-treated PLWH and to examine the specific mechanisms by which these changes mediate the development of cognitive dysfunction, degeneration, and other NPAE. Contributions should focus on the impact of HIV or ART on the interactions between one or more of these cell types and/or how those interactions alter cellular function and the development of HIV infection. This Topic especially welcomes novel hypotheses regarding the etiology of NeuroHIV and identifying potential therapeutic strategies to be pursued in the coming years.
This Research Topic will focus on our developing understanding of the role of neuroimmune communication in neurological disorders in people living with HIV (PLWH) during the era of anti-retroviral therapy ART.
HIV infection has been transformed from a terminal diagnosis to a chronic disease, greatly extending the lives of infected individuals with access to ART. However, this success has also led to new health challenges, including the development of long-term neurological dysfunction. Prior to ART, infected individuals showed rampant neuroinflammation and significant neuronal death associated with high rates of dementia, but with ART the neuropathology associated with HIV infection has become more complex and subtler.
However, even full suppression of viral replication with the use of cART with good CNS penetrance, minor neurocognitive dysfunction, depression, and other neuropsychiatric adverse events (NPAE) remain prevalent. This suggests that the etiology of these conditions is not solely derived from viral replication. Instead, data suggest that NeuroHIV stems from dysfunction in the neuroimmune cross-talk that regulates the interactions between neural circuits, support glia, and the HIV-infected cells in the brain. Moreover, recent evidence suggests that antiretroviral drugs, both alone and through their interaction with other therapeutics, may also contribute to changes in neuroimmune communication and neurological dysfunction. These problems are particularly acute for the aging HIV-infected population, as these individuals are often on long-term ART in combination with other therapeutics.
Proper CNS function is maintained by complex interactions between neurons, astrocytes, microglia, and CNS macrophages. Cytokines and neurotrophic factors produced by supporting cells are central to neuronal health and effective, bidirectional neuroimmune communication. These interactions facilitate synapse formation and dissolution, modulate neurotransmission, and provide neuronal protection. Dysregulation of these interactions can result from HIV- or ART-associated changes in immune cell functions such as chemotaxis, phagocytosis of extracellular aggregates and damaged neurons, production of cytokines or trophic factors, maintenance of CNS vasculature, or alterations in neurotransmitter uptake. These changes can lead to the development of neuroinflammation and neuronal dysfunction and degeneration, significantly impairing the activity of neuronal circuits and resulting in behavioral changes and cognitive deficits.
The aim of this Research Topic is to more precisely define the specific changes in neuroimmune communication that are occurring in ART-treated PLWH and to examine the specific mechanisms by which these changes mediate the development of cognitive dysfunction, degeneration, and other NPAE. Contributions should focus on the impact of HIV or ART on the interactions between one or more of these cell types and/or how those interactions alter cellular function and the development of HIV infection. This Topic especially welcomes novel hypotheses regarding the etiology of NeuroHIV and identifying potential therapeutic strategies to be pursued in the coming years.