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...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Servizo Galego de Saúde (SERGAS) |
| Repository: | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| OAI Identifier: | oai:runa.sergas.gal:20.500.11940/21537 |
| Online Access: | https://portalcientifico.sergas.gal//documentos/6522c7d7ec1a10197ffd9133 http://hdl.handle.net/20.500.11940/21537 |
| Access Level: | Open access |
| Keyword: | Humans HIV Infections Genomics Neurocognitive Disorders HIV-1 AIDS Dementia Complex AS Santiago IDIS CHUS |
| _version_ | 1878739950242889728 |
|---|---|
| author | Borrajo López, Ana |
| author2 | Pérez-Rodríguez, D. Fernández-Pereira, C. Prieto González, José María Agis Balboa, Roberto Carlos |
| author2_role | author author author author |
| author_browse | Agis Balboa, Roberto Carlos Borrajo López, Ana Fernández-Pereira, C. Prieto González, José María Pérez-Rodríguez, D. |
| author_facet | Borrajo López, Ana Pérez-Rodríguez, D. Fernández-Pereira, C. Prieto González, José María Agis Balboa, Roberto Carlos |
| author_role | author |
| collection | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_cafe9b9ce4ebe6b3e28e793e1f2ae53f |
| institution | Servizo Galego de Saúde (SERGAS) |
| instname_str | Servizo Galego de Saúde (SERGAS) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:runa.sergas.gal:20.500.11940/21537 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| reponame_str | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| 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 |
| 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 | 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_short | 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 |
| 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 |
| url | https://portalcientifico.sergas.gal//documentos/6522c7d7ec1a10197ffd9133 http://hdl.handle.net/20.500.11940/21537 |