HIV-Associated Neurocognitive Disorders

1st Edition - February 21, 2024
Editors: Guoku Hu, Huangui Xiong, Shilpa Buch
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 7 4 4 - 7
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 7 4 5 - 4

HIV-Associated Neurocognitive Disorders (HAND) presents a complex and evolving challenge in the context of HIV-1 infection and treatment. This comprehensive volume dives into the… Read more

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HIV-Associated Neurocognitive Disorders (HAND) presents a complex and evolving challenge in the context of HIV-1 infection and treatment. This comprehensive volume dives into the clinical manifestations, molecular and cellular mechanisms, and therapeutic strategies underlying HAND and its associated comorbidities. This book brings together cutting-edge research and clinical insights, making it an essential resource for researchers, clinicians, and students engaged in HIV-related studies and neurocognitive research. This resource also aims to advance our understanding of HAND to contribute to the development of novel diagnostic tools and therapeutic interventions for improved patient outcomes.

Cover image
Title page
Table of Contents
Copyright
Contributors
The neuroHIV journey
Preface
Chapter 1. An overview of the mechanisms of HIV-1 infection, latency, pathogenesis, and eradication strategies from the CNS
Introduction
Main HIV-1 reservoirs
HIV latency in the CNS
HIV-1 reservoir and pathogenesis in the CNS
Strategies to eradicate HIV-1 from the CNS reservoirs
Future prospectives
Conclusions
Chapter 2. Central nervous system complications of human immunodeficiency virus infection
Introduction
HIV molecular biology
HIV life cycle
Antiretroviral therapy
HIV immunopathogenesis
HIV and CD4+ T cells
End organ disease
Nervous system comorbidities
HIV-associated neurocognitive disorders
Adjunctive therapies for NeuroHIV
Future prospective
Conflict of interest statement
Chapter 3. Health literacy in HIV-associated neurocognitive disorders
What is health literacy?
Measurement of health literacy
Health literacy in HIV disease
HIV and the brain
Health literacy and the brain
HIV, health literacy, and neuropsychological functioning
Chapter 4. Neuroimaging insights into the CNS effects of HIV infection
Introduction
Brain structure: white matter, basal ganglia, and cortical involvement
Brain metabolites: support for neuronal damage and neuroinflammation
Brain activity: altered function and connectivity at rest and during tasks
Brain metabolism and microglial activation: evidence for neuroinflammation
Considerations and future directions
Chapter 5. Endolysosome iron: Early and upstream subcellular organellar events associated with HAND
Introduction
Iron and endolysosomes
Iron and mitochondria
Iron and endoplasmic reticulum
Iron and nuclei
Conclusions
Author contributions statement
Chapter 6. White matter loss and oligodendrocyte dysfunction in HAND
Introduction
The importance of the myelin membrane in nervous system function
White matter dysfunction in HIV before and after antiretroviral therapy
How does HIV cause cellular stress in oligodendrocytes?
Models of HIV-HAND
Effects of ARVs on oligodendrocyte maturation and myelination
Conclusion
Chapter 7. Pathogenesis of HIV-associated pain
Neuropathology in pain circuits
Etiological causes
Potential pathogenic mechanisms
Conclusion
Chapter 8. Neuropathogenesis of HIV-associated neuropathic pain
Introduction
Neuropathic pain processing
HIV-associated sensory neuropathy
HIV-associated pain models
Factors contributing to multi-morbidity in HIV chronic pain
Conclusion
Chapter 9. Neuropathic pain in HIV and the role of the autophagy pathway
Introduction—neuropathic pain
Neuropathic pain and HIV
Therapeutic treatments against neuropathic pain
Autophagy and pain
Autophagy and alleviation of neuropathic pain
Autophagy, HIV-NP, and opioid abuse
Conclusion
Chapter 10. Host peripheral immune dynamics increase HIV-associated neurocognitive disorders incidence and progression
Introduction to HAND pathogenesis
Peripheral inflammation and HIV
Barrier dysfunction during HIV
Microbial translocation and HAND
HIV and microbiome
Microbiome and monocytes
Monocytes and HAND
Gut inflammation and CNS monocyte trafficking
Peripheral inflammation and BBB permeability
Neurogenesis and neurodegeneration
Inflammation, neurogenesis, and HAND
Conclusions
Chapter 11. The role of immunometabolism in HIV-associated depression and cognitive impairment
Introduction
Immunometabolism in HIV-associated depression
Pathways contributing to depression in PWH
Inflammation in HIV-associated depression
Factors associated with depression in PWH
Immunometabolism in HAND
Inflammation in HAND
The role of immunity in HAND
Immune activation and neuroinflammation in HAND
Factors associated with HAND in PWH
Summary
Chapter 12. Role of extracellular viral regulatory proteins in neuropathogenesis
Introduction
Gp120
Tat
Vpr
Nef
Conclusions
Chapter 13. Role of inflammasomes in HIV-1 and drug abuse-mediated neuroinflammation
Introduction
Inflammasomes
Types of inflammasomes
Neuroinflammation
Neuroinflammation in HIV-1 infection and drug use disorders
Role of inflammasomes in HIV infection and drug use disorders
Role of microglia in inflammasome activation
Role of astrocytes in inflammasome activation
Role of neurons in inflammasome activation
Roles of extracellular vesicles in inflammasome activation
Targeting inflammasomes as therapeutics
Pharmacological inhibition of inflammasome
Indirect pharmacological inhibitors of the inflammasome signaling pathway
Direct pharmacological inhibitors of the inflammasome signaling pathway
Pharmacological inhibitors of the inflammasome signaling components
Outstanding questions
Conclusion and future perspectives
Chapter 14. The contribution of myeloid cells to HIV neuropathogenesis
Introduction
Monocytes
Macrophages/microglia
Conclusion
Gaps in knowledge and suggested future research
Chapter 15. Immunophilin ligands modulate phagocytosis and viral replication in HIV-infected macrophages
Immunophilin ligands and neuro-HIV
IPLs impacting HIV replication, and the role of IL-6
Structural and functional alterations in macrophages by HIV and IPLs
Conclusion
Chapter 16. Immunometabolic mechanisms of HIV-associated neurocognitive disorders and traumatic brain injury: Commonalities and contrasts between chronic and acute neurodegenerative pathologies
Introduction
Metabolic signatures
Brief intro to glycolysis and oxidative phosphorylation
Metabolic signature of HAND
Metabolic signature of TBI
Metabolic signatures conclusion and future directions
Inflammatory gene expression and transcription factors
Brain macrophages
Astroglia
Glia to glia and glia to neuron cross-talk
Mitochondria in HAND and TBI
Need for cutting-edge translational studies
Potential therapeutic strategies targeting immunometabolism in HAND and TBI
Conclusion
Chapter 17. Endolysosome dysfunction in HAND
Introduction
Physiological importance of endolysosomes
Endolysosomes and neuronal function
Endolysosome dysfunction and neuronal injury in HAND
Endolysosomes and immune responses
Endolysosome dysfunction and neuroinflammation in HAND
Conclusion and perspective
Chapter 18. Evolving biomarkers for HIV-associated neurocognitive disorders (HAND)
Introduction
Definition of HAND
Biomarkers of HAND
Biomarker profiles using machine learning
Chapter 19. Intracellular innate immunity against HIV-1 infection
Host innate immunity against HIV-1 infection
Intracellular innate immunity against HIV-1 in macrophages
Roles of dendritic cells in HIV-1 infection
Anti-HIV-1 activities by natural killer cells
Anti-HIV-1 activities of nonimmune cells
DNA sensor activation-mediated HIV-1 inhibition
Conclusion
Chapter 20. NeuroHIV and the glymphatic system
Introduction
NeuroHIV
The glymphatic system
Single nucleotide polymorphisms in aqp4
Summary
Chapter 21. The p75 neurotrophin receptor: Emerging role in the pathogenesis of mature synapses in human immunodeficiency virus–associated neurocognitive disorders
Introduction
The neurotrophins
Neurotrophin receptor complex
Activation of p75NTR and proapoptotic intracellular signaling
Diverse roles for p75NTR at the synapse
HIV-associated neurocognitive disorder and p75NTR
Small molecules
Concluding remarks
Chapter 22. The role of HIV-associated neuroendocrine dysfunction in HAND
Introduction
Systemic endocrine dysfunction in the pre-ART era
The rise of neuroendocrine dysfunction in the post-ART era
HIV-mediated dysfunction of the hypothalamic-pituitary-adrenal axis
HIV-mediated dysfunction of the hypothalamic–pituitary–gonadal axis
Reciprocal effects of steroid hormones on HIV
Conclusion
Chapter 23. Impact of SARS-CoV-2/COVID-19 on HIV-1-associated neurocognitive disorders
Introduction
Comparisons between HIV-1 and SARS-CoV-2
HIV-1 in the CNS
SARS-CoV-2 in the CNS
SARS-CoV-2 infection-mediated impacts on PLWH
Mechanisms involved in the impact of COVID-19 on PLWH
Challenges in the HIV-1-AIDS/SARS-CoV-2-COVID-19 syndemic
Chapter 24. Molecular mechanisms of dopaminergic transmission in NeuroHIV
Introduction
Dysregulation of dopaminergic transmission in HIV-associated neurocognitive disorders
HIV-1 viral proteins target monoamine transporters
HIV-1 Tat protein interacts with DAT allosterically
HIV-1 vulnerability to substance abuse
Conclusion
Chapter 25. The effect of substance misuse on HIV persistence in the CNS: Epidemiological, immunological, and molecular considerations
Introduction
Common factors affecting the reservoir
The role of stigma in substance misuse and HIV
Epidemiology of substance misuse in HIV patients
Effect of substances of misuse on HIV CNS immunopathology
Molecular effects of substance misuse on HIV transcription and replication
Caveats
Overall conclusions
Chapter 26. Extracellular vesicles in alcohol and tobacco-induced NeuroAIDS
General background
Extracellular vesicles/exosomes
EVs in the pathogenesis of HIV and drugs abuse
EVs in biomarker discovery
EVs in drug delivery
Chapter 27. NeuroHIV in the context of opioid use disorder: a complex and evolving relationship
The opioid crisis
Neuropathology of opioid use in people with HIV
HIV and opioids and blood–brain barrier
Antiretroviral delivery to the brain
Adherence differences in setting of opioid use
Conclusions and future directions
Chapter 28. Impairment of cholesterol homeostasis induced by Nef-containing extracellular vesicles as a factor in HAND pathogenesis
Introduction
Nef impairs cholesterol homeostasis
Current explanations of HAND pathogenesis
Cholesterol homeostasis and CNS disease
Cholesterol-targeting therapeutic approaches for HAND
Conclusions
Chapter 29. Long noncoding RNAs in immune response, viral infection, and opioid use
Introduction
lncRNAs and immune responses
lncRNAs and HIV infection
lncRNAs and other viral infections
LncRNAs and antiretroviral therapy
LncRNAs and drug abuse
Conclusions and perspectives
Chapter 30. Using cross-species behavioral tools to determine mechanisms contributing to HIV-associated neurocognitive disorder and comorbid substance use
What is HAND?
Difficulties related to HAND diagnosis and treatment
Using a RDoC approach toward better characterizing HAND toward tighter neural substrates
Rodent models of HIV and assessment for HAND
Additional impact of substance use in HAND
Cognitive performance of rodent models of HIV after SU treatment
Discussion
Promise for precision medicine and individualized treatment
Limitations
Conclusions and suggestions for testing in the future
Chapter 31. Therapeutic potential of curcumin in HIV-1-associated neurocognitive disorders
Introduction
Therapeutics strategy against HAND
Curcumin as a potential therapeutic agent against HAND
Obstacles and prospects
Summary
Chapter 32. Targeting the endocannabinoid system in HAND
Background
The endocannabinoid system
HIV-associated neurocognitive disorder
Clinical and preclinical evidence of therapeutic properties of cannabinoids in HAND
Conclusion and future directions
Chapter 33. Predicting the effectiveness of combination treatment of dolutegravir and fluoxetine for depressive disorders in HIV
Introduction
Computational-based method for predicting drug–drug interactions
HIV-associated neurocognitive impairment
Conclusions
Chapter 34. Antiretroviral therapy and its cerebral vascular toxicity
Introduction
The BBB and HIV infection
ART-associated toxicity
ART and BBB dysfunction
Future directions
Discussion
Conclusion
Chapter 35. Strategies for HIV-1 elimination
Introduction
Concluding remarks
Index

Guoku Hu

Dr. Hu is an Associate Professor in the Department of Pharmacology and Experimental Neuroscience at University of Nebraska Medical Center. His work is focused on mRNA biology, with the ultimate goal of elucidating their functional aspects in drug addiction, and also to identify novel therapeutic strategies that could enhance neuronal function and survival in patients afflicted with these disorders.

Affiliations and expertise

Associate Professor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

Huangui Xiong

Dr. Xiong is a Professor in the Department of Pharmacology and Experimental Neuroscience at University of Nebraska Medical Center and leader of the University of Nebraska Medical Center Neurophysiology Laboratory in the Center for Neurovirology and Neurodegenerative Disorders. He is a neuroelectrophysiologist working in the field of NeuroAIDS (the neurological complications of AIDS), which include neurocognitive impairment and HIV-associated dementia (HAD). Current research in his laboratory studies molecular and cellular mechanisms underlying HIV-1-associated cellular and synaptic dysfunction and injury, with the ultimate goal of identifying potential target(s) for the development of therapeutic strategies. Dr. Xiong is the author of Current Laboratory Methods in Neuroscience Research (Springer) and has additionally authored many book chapters.

Affiliations and expertise

Professor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

Shilpa Buch

Dr. Buch is a Professor and Executive Vice-Chair of the Department of Pharmacology and Experimental Neuroscience at University of Nebraska Medical Center. Her research focuses on understanding the neuropathogenesis of HIV/SIV infection using cell culture, rodents and macaques as model systems. She is the director of the Nebraska Center for Substance Abuse Research, the mission of which is to promote and enhance drug abuse research and mentor trainees in this area. Dr. Buch is a Member of the European Academy of Sciences, and a Member of the Royal Academy of Belgium.

Affiliations and expertise

Professor and Senior Executive Vice-Chair, Department of Pharmacology and Experimental Neuroscience, Director – Nebraska Center for Substance Abuse Research, University of Nebraska Medical Center, Omaha, Nebraska, USA