Developments in Neuroprotection for HIV-Associated Neurocognitive Disorders (HAND)

Kolson, Dennis L.

doi:10.1007/s11904-022-00612-2

Cited by 19 publications

(19 citation statements)

References 128 publications

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“…The mechanisms underlying this risk are not fully understood but may involve shared neuroinflammatory pathways. [10] Neurological opportunistic infections: • Opportunistic infections that affect the central nervous system, such as toxoplasmosis or cryptococcal meningitis, can contribute to cognitive impairment in individuals with HIV. [11] Psychosocial factors: • Psychosocial factors, including stress, depression, and social isolation, can impact cognitive function.…”

Section: Discussionmentioning

confidence: 99%

HIV-related neurocognitive disorders: Diagnosis, Treatment, and Mental Health Implications: A Review

Elendu,

Aguocha,

Okeke

et al. 2023

Medicine

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HIV-related neurocognitive disorders (HAND) have emerged as a significant concern in the context of HIV infection. This article provides a comprehensive overview of the diagnosis, treatment, and mental health implications associated with HAND. Diagnosis of HAND involves a multifaceted approach, combining clinical assessments, neurocognitive testing, and neuroimaging techniques. Various screening tools and standardized assessments have been developed to aid in the early detection and monitoring of HAND. Timely diagnosis allows for appropriate interventions and personalized treatment strategies. Treatment for HAND encompasses a multidisciplinary approach targeting different aspects of cognitive impairment. Antiretroviral therapy (ART) remains the cornerstone of treatment, effectively reducing viral load and preventing further neurocognitive decline. Adjunctive therapies, including cognitive rehabilitation, pharmacological interventions, and psychosocial support, play crucial roles in managing cognitive symptoms and enhancing overall quality of life. Mental health implications associated with HAND are profound and require special attention. Individuals with HAND are at higher risk of experiencing psychological distress, depression, anxiety, and reduced social functioning. Integrated care models that address physical and mental health aspects are vital in optimizing treatment outcomes and promoting mental well-being in this population. Furthermore, this paper highlights the need for ongoing research to unravel the underlying mechanisms of HAND and develop targeted interventions. Identifying risk factors, understanding the impact of HIV on the brain, and exploring novel treatment modalities are essential areas of focus. Additionally, living with HAND social and cultural aspects must be considered to ensure equitable access to care and support for all affected individuals.

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Section: Discussionmentioning

confidence: 99%

HIV-related neurocognitive disorders: Diagnosis, Treatment, and Mental Health Implications: A Review

Elendu,

Aguocha,

Okeke

et al. 2023

Medicine

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“…There is some evidence of higher Central Nervous System Penetrance Effectiveness (CPE) score of cART regimens showing protection against HAND but the clinical picture is complicated by neuropsychiatric side effects of these regimens [40]. The recent introduction of integrase strand transfer inhibitors (INSTI) such as dolutegravir was initially promising due to effectiveness in blocking viral replication but current trial evidence including a 96 week placebo controlled doubleblind intensification study does not suggest any significant effect on HAND [40]. One South African study (2023) suggested reduction in cognitive impairment on commencing dolutegravir but was undertaken in treatment na€ ıve patients commencing cART without a control arm [41].…”

Section: Interventional Approachesmentioning

confidence: 99%

“…There have been recent randomized controlled trials of lithium, and B vitamins as adjuvant treatments in cART-treated PWHA, both of which were unsuccessful [39]. There is some evidence of higher Central Nervous System Penetrance Effectiveness (CPE) score of cART regimens showing protection against HAND but the clinical picture is complicated by neuropsychiatric side effects of these regimens [40]. The recent introduction of integrase strand transfer inhibitors (INSTI) such as dolutegravir was initially promising due to effectiveness in blocking viral replication but current trial evidence including a 96 week placebo controlled double-blind intensification study does not suggest any significant effect on HAND [40].…”

Section: Interventional Approachesmentioning

confidence: 99%

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Paddick,

Mukaetova-Ladinska

2023

Current Opinion in Psychiatry

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Purpose of review We reviewed recent literature on prevalence and interventional approaches for cognitive impairment in the context of HIV infection alongside current controversies and challenges around its nomenclature, screening, and diagnosis. Recent findings Prevalence estimates for HIV-associated neurocognitive disorder (HAND) indicate that HAND remains highly prevalent despite combination antiretroviral treatment (cART) widely used. The available data are heterogeneous, particularly in sub-Saharan Africa (SSA) where recent reviews indicate substantial heterogeneity, wide prevalence estimates and lack of data from the majority SSA countries, despite them currently experiencing the greatest burden worldwide of both HIV and HAND. Several alternative approaches to diagnosis and classification of cognitive impairment in HIV have been published, taking into account changing clinical phenotypes. Summary Cognitive impairment remains a significant challenge in the care of people living with HIV despite advances in treatment. Ongoing controversies exist around nomenclature and classification, screening measures, and the phenotype and aetiology of observed impairments. Two current areas of research priority and focus include understanding current phenotypes of individuals living and ageing with treated HIV and differing levels of risk for HAND in these phenotypes, alongside the effects of commonly occurring comorbidities. The current evidence base for interventional approaches is limited, but growing. The most promising avenues appear to be multidisciplinary. These are currently focussed on high income settings rather than SSA where the majority of people living with HIV, and affected by cognitive impairment in the context of HIV, currently reside.

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“…Within days of infection, HIV-infected blood monocytes breach the blood-brain barrier (BBB), activating perivascular macrophages and microglia, the principal productively infected cells in the CNS [1,12,13]. The establishment of a latent viral reservoir within microglia underlies the persistent neuroinflammation and immune activation characteristic of HAND, which is lessened but not abolished by cART [1,14].…”

Section: Introductionmentioning

confidence: 99%

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells

Kaur,

Minchella,

Alvarez-Carbonell

et al. 2023

IJMS

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HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20–30%, with the most pronounced effects in latently infected HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron–sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

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Developments in Neuroprotection for HIV-Associated Neurocognitive Disorders (HAND)

Cited by 19 publications

References 128 publications

HIV-related neurocognitive disorders: Diagnosis, Treatment, and Mental Health Implications: A Review

HIV-related neurocognitive disorders: Diagnosis, Treatment, and Mental Health Implications: A Review

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells

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