Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review

HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and...

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Detalhes bibliográficos
Autores: Borrajo López, Ana, Pérez-Rodríguez, D., Fernández-Pereira, C., Prieto González, José María, Agis Balboa, Roberto Carlos
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositório:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21537
Acesso em linha:https://portalcientifico.sergas.gal//documentos/6522c7d7ec1a10197ffd9133
http://hdl.handle.net/20.500.11940/21537
Access Level:Acceso aberto
Palavra-chave:Humans
HIV Infections
Genomics
Neurocognitive Disorders
HIV-1
AIDS Dementia Complex
AS Santiago
IDIS
CHUS
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spelling Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review Borrajo López, Ana Pérez-Rodríguez, D. Fernández-Pereira, C. Prieto González, José María Agis Balboa, Roberto Carlos Humans HIV Infections Genomics Neurocognitive Disorders HIV-1 AIDS Dementia Complex AS Santiago IDIS CHUS HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases. This work was partially supported by: (i) Instituto de Salud Carlos III (ISCIII) through the project PI18/01311 (co-funded by European Regional Development Fund (FEDER), A way to make Europe, UE) to R.C. Agis-Balboa and (ii) by a Ramon & Cajal grant [RYC2021-031699-I] to A.B. https://portalcientifico.sergas.gal//documentos/6522c7d7ec1a10197ffd9133 http://hdl.handle.net/20.500.11940/21537
title Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
spellingShingle Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
Borrajo López, Ana
Humans
HIV Infections
Genomics
Neurocognitive Disorders
HIV-1
AIDS Dementia Complex
AS Santiago
IDIS
CHUS
title_short Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
title_full Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
title_fullStr Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
title_full_unstemmed Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
title_sort Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review
author Borrajo López, Ana
author_facet Borrajo López, Ana
Pérez-Rodríguez, D.
Fernández-Pereira, C.
Prieto González, José María
Agis Balboa, Roberto Carlos
author_role author
author2 Pérez-Rodríguez, D.
Fernández-Pereira, C.
Prieto González, José María
Agis Balboa, Roberto Carlos
author2_role author
author
author
author
topic Humans
HIV Infections
Genomics
Neurocognitive Disorders
HIV-1
AIDS Dementia Complex
AS Santiago
IDIS
CHUS
topic_facet Humans
HIV Infections
Genomics
Neurocognitive Disorders
HIV-1
AIDS Dementia Complex
AS Santiago
IDIS
CHUS
description HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases.
publishDate 2023
format article
url https://portalcientifico.sergas.gal//documentos/6522c7d7ec1a10197ffd9133
http://hdl.handle.net/20.500.11940/21537
eu_rights_str_mv openAccess
institution Servizo Galego de Saúde (SERGAS)
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
instname_str Servizo Galego de Saúde (SERGAS)
_version_ 1878739950242889728
publishDateSort 2023
author_browse Agis Balboa, Roberto Carlos
Borrajo López, Ana
Fernández-Pereira, C.
Prieto González, José María
Pérez-Rodríguez, D.
score 6,8972664

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