Neurological impact of HIV/AIDS and substance use alters brain function and structure

Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV infection is often assoc...

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Main Authors: James Haorah, Samikkannu Malaroviyam, Hemavathi Iyappan, Thangavel Samikkannu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1505440/full
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author James Haorah
Samikkannu Malaroviyam
Hemavathi Iyappan
Thangavel Samikkannu
author_facet James Haorah
Samikkannu Malaroviyam
Hemavathi Iyappan
Thangavel Samikkannu
author_sort James Haorah
collection DOAJ
description Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV infection is often associated with substance use, which promotes HIV transmission and viral replication and exacerbates HANDs even in the era of cART. Thus, the comorbid effects of substance use exacerbate the neuropathogenesis of HANDs. Unraveling the mechanism(s) of this comorbid exacerbation at the molecular, cell-type, and brain region levels may provide a better understanding of HAND persistence. This review aims to highlight the comorbid effects of HIV and substance use in specific brain regions and cell types involved in the persistence of HANDs. This review includes an overview of post-translational modifications, alterations in microglia-specific biomarkers, and possible mechanistic pathways that may link epigenomic modifications to functional protein alterations in microglia. The impairment of the microglial proteins that are involved in neural circuit function appears to contribute to the breakdown of cellular communication and neurodegeneration in HANDs. The epigenetic modification of N-terminal acetylation is currently understudied, which is discussed in brief to demonstrate the important role of this epigenetic modification in infected microglia within specific brain regions. The discussion also explores whether combined antiretroviral therapy is effective in preventing HIV infection or substance-use-mediated post-translational modifications and protein alterations in the persistence of neuropathogenesis in HANDs.
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spelling doaj-art-b256300e95fa442ba5a3850faed3983a2025-01-07T06:50:34ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011110.3389/fmed.2024.15054401505440Neurological impact of HIV/AIDS and substance use alters brain function and structureJames HaorahSamikkannu MalaroviyamHemavathi IyappanThangavel SamikkannuHuman immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV infection is often associated with substance use, which promotes HIV transmission and viral replication and exacerbates HANDs even in the era of cART. Thus, the comorbid effects of substance use exacerbate the neuropathogenesis of HANDs. Unraveling the mechanism(s) of this comorbid exacerbation at the molecular, cell-type, and brain region levels may provide a better understanding of HAND persistence. This review aims to highlight the comorbid effects of HIV and substance use in specific brain regions and cell types involved in the persistence of HANDs. This review includes an overview of post-translational modifications, alterations in microglia-specific biomarkers, and possible mechanistic pathways that may link epigenomic modifications to functional protein alterations in microglia. The impairment of the microglial proteins that are involved in neural circuit function appears to contribute to the breakdown of cellular communication and neurodegeneration in HANDs. The epigenetic modification of N-terminal acetylation is currently understudied, which is discussed in brief to demonstrate the important role of this epigenetic modification in infected microglia within specific brain regions. The discussion also explores whether combined antiretroviral therapy is effective in preventing HIV infection or substance-use-mediated post-translational modifications and protein alterations in the persistence of neuropathogenesis in HANDs.https://www.frontiersin.org/articles/10.3389/fmed.2024.1505440/fullHIVdrugs of abusemicrogliaCARTHANDs
spellingShingle James Haorah
Samikkannu Malaroviyam
Hemavathi Iyappan
Thangavel Samikkannu
Neurological impact of HIV/AIDS and substance use alters brain function and structure
Frontiers in Medicine
HIV
drugs of abuse
microglia
CART
HANDs
title Neurological impact of HIV/AIDS and substance use alters brain function and structure
title_full Neurological impact of HIV/AIDS and substance use alters brain function and structure
title_fullStr Neurological impact of HIV/AIDS and substance use alters brain function and structure
title_full_unstemmed Neurological impact of HIV/AIDS and substance use alters brain function and structure
title_short Neurological impact of HIV/AIDS and substance use alters brain function and structure
title_sort neurological impact of hiv aids and substance use alters brain function and structure
topic HIV
drugs of abuse
microglia
CART
HANDs
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1505440/full
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AT samikkannumalaroviyam neurologicalimpactofhivaidsandsubstanceusealtersbrainfunctionandstructure
AT hemavathiiyappan neurologicalimpactofhivaidsandsubstanceusealtersbrainfunctionandstructure
AT thangavelsamikkannu neurologicalimpactofhivaidsandsubstanceusealtersbrainfunctionandstructure