New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment

Angelovich, Thomas A; Churchill, Melissa; Wright, Edwina; Brew, Bruce J.

doi:10.1007/7854_2019_126

Cited by 8 publications

(3 citation statements)

References 239 publications

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“…If systemic HIV-1 replication is not controlled by ART, localized HIV-1-CNS replication and infection results in HIV-1 encephalitis and dementia (Gatanaga et al, 1999 ; Bingham et al, 2011 ; Gelman et al, 2013 ; Gelman, 2015 ; de Almeida et al, 2017 ; Mangus et al, 2018 ). However, in the current ART era, CNS damage is mild due to controlled peripheral and CNS replication as well as limited HIV-1 infection; despite this, 50% of the HIV-1-infected individuals still show significant signs of cognitive impairment, but the mechanism of CNS dysfunction is unknown (Eggers et al, 2017 ; Yoshimura, 2017 ; Bandera et al, 2019 ; Fernandes and Pulliam, 2019 ; Kim-Chang et al, 2019 ; Paul, 2019 ; Portilla et al, 2019 ; Swinton et al, 2019 ; Angelovich et al, 2020 ). Several groups have proposed that CNS damage in the current ART era corresponds to a combination of HIV-1 reservoirs within the brain, low level expression and secretion of viral proteins, as well as associated inflammation (Wong and Yukl, 2016 ; Veenstra et al, 2017 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Górska

Eugenín

2020

Front. Cell. Infect. Microbiol.

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Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS). HIV-1 and viral proteins compromise glutamate synaptic transmission, resulting in poor cell-to-cell signaling and bystander toxicity. In this study, we identified that myeloid HIV-1-brain reservoirs survive in Glu and glutamine (Gln) as a major source of energy. Thus, we found a link between synaptic compromise, metabolomics of viral reservoirs, and viral persistence. In the current manuscript we will discuss all these interactions and the potential to achieve eradication and cure using this unique metabolic profile.

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Section: Introductionmentioning

confidence: 99%

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Górska

Eugenín

2020

Front. Cell. Infect. Microbiol.

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“…These findings support the role of epigenetic perturbations of monocytes in HIV-associated CI and the potential to identify immuno-epigenetic signatures that could be used to research novel therapeutic approaches. The results of this small study still need to be validated in larger cohorts, preferably with pure subsets of monocytes such as microglia, which play a vital role in brain dysfunction [ 34 ].…”

Section: Epigenetic Epidemiologic Studies Of Pwhmentioning

confidence: 99%

Epigenome-wide epidemiologic studies of human immunodeficiency virus infection, treatment, and disease progression

et al. 2022

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Despite significant advances in the treatment and care of people with HIV (PWH), several challenges remain in our understanding of disease pathogenesis to improve patient care. HIV infection can modify the host epigenome and as such can impact disease progression, as well as the molecular processes driving non-AIDS comorbidities in PWH. Epigenetic epidemiologic studies including epigenome-wide association studies (EWAS) offer a unique set of tools to expand our understanding of HIV disease and to identify novel strategies applicable to treatment and diagnosis in this patient population. In this review, we summarize the current state of knowledge from epigenetic epidemiologic studies of PWH, identify the main challenges of this approach, and highlight future directions for the field. Emerging epigenetic epidemiologic studies of PWH can expand our understanding of HIV infection and health outcomes, improve scientific validity through collaboration and replication, and increase the coverage of diverse populations affected by the global HIV pandemic. Through this review, we hope to highlight the potential of EWAS as a tool for HIV research and to engage more investigators to explore its application to important research questions.

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“…Although successful antiretroviral therapy (ART) has substantially reduced the incidence of HIV-associated dementia, milder forms of HIV-associated neurocognitive disorders (HAND) continue to be a prevalent comorbidity associated with HIV. [1][2][3][4][5] Current observations of HIVassociated neurocognitive impairment (NCI) persist despite the use of effective ART. However, recent studies suggest that non-HIV factors, such as comorbidities and aging, may have become the primary contributors to NCI in adults with HIV.…”

Section: Introductionmentioning

confidence: 99%

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland

Lai,

Treisman,

Celentano

et al. 2023

Int J STD AIDS

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Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association. Methods: We analyzed data from 788 adults (≥45 years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis. Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14 μmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10 years, suggesting that extended cocaine use may have a substantial influence on cognitive performance. Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment.

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New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment

Cited by 8 publications

References 239 publications

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Epigenome-wide epidemiologic studies of human immunodeficiency virus infection, treatment, and disease progression

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland

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