HIV, smoking, and the brain: a convergence of neurotoxicities

Abstract Purpose of review The purpose of this review is to characterize the combined effects of tobacco smoking and human immunodeficiency virus (HIV) infection in people with HIV (PWH) and identify possible therapeutic targets through shared mechanisms for neurotoxicity. Recent findings HIV and to...

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Main Authors: Benjamin L. Orlinick, Shelli F. Farhadian
Format: Article
Language:English
Published: BMC 2025-02-01
Series:AIDS Research and Therapy
Subjects:
Online Access:https://doi.org/10.1186/s12981-025-00714-y
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author Benjamin L. Orlinick
Shelli F. Farhadian
author_facet Benjamin L. Orlinick
Shelli F. Farhadian
author_sort Benjamin L. Orlinick
collection DOAJ
description Abstract Purpose of review The purpose of this review is to characterize the combined effects of tobacco smoking and human immunodeficiency virus (HIV) infection in people with HIV (PWH) and identify possible therapeutic targets through shared mechanisms for neurotoxicity. Recent findings HIV and tobacco smoke can exert neurotoxicity through shared mechanisms such as brain volume changes, microglial dysregulation, and dysregulation of the cholinergic anti-inflammatory pathway (CAP) through the alpha7-nicotinic acetylcholine receptor (nAChR). Evidence also suggests the potential for synergistic effects of HIV and tobacco smoking on neurotoxicity. Summary People with HIV (PWH) are disproportionately affected by both neurocognitive impairment (NCI) and tobacco smoking compared to the general population. Both HIV and tobacco smoking are known to have neurotoxic effects and have the potential for clinically significant impacts on brain health and cognitive functioning. Less, however, is known about how PWH may be uniquely affected by the interactive neurotoxic effects of both HIV and tobacco smoking. Evidence suggests that smoking and HIV can have synergistic effects on neurotoxicity and NCI in PWH. Some mechanisms for neurotoxicity include increased oxidative stress from microglial activation and dysfunction in the alpha7- nAChR cholinergic anti-inflammatory pathway leading to increased neuroinflammation and neuronal apoptosis. Mechanisms may vary by cell type and brain region, however, and there is a need for more human-facing, longitudinal studies on smoking in PWH.
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spelling doaj-art-ee1c7201e6604916968f57d6904488de2025-02-09T12:55:20ZengBMCAIDS Research and Therapy1742-64052025-02-012211910.1186/s12981-025-00714-yHIV, smoking, and the brain: a convergence of neurotoxicitiesBenjamin L. Orlinick0Shelli F. Farhadian1Yale School of Medicine, Section of Infectious DiseasesYale School of Medicine, Section of Infectious DiseasesAbstract Purpose of review The purpose of this review is to characterize the combined effects of tobacco smoking and human immunodeficiency virus (HIV) infection in people with HIV (PWH) and identify possible therapeutic targets through shared mechanisms for neurotoxicity. Recent findings HIV and tobacco smoke can exert neurotoxicity through shared mechanisms such as brain volume changes, microglial dysregulation, and dysregulation of the cholinergic anti-inflammatory pathway (CAP) through the alpha7-nicotinic acetylcholine receptor (nAChR). Evidence also suggests the potential for synergistic effects of HIV and tobacco smoking on neurotoxicity. Summary People with HIV (PWH) are disproportionately affected by both neurocognitive impairment (NCI) and tobacco smoking compared to the general population. Both HIV and tobacco smoking are known to have neurotoxic effects and have the potential for clinically significant impacts on brain health and cognitive functioning. Less, however, is known about how PWH may be uniquely affected by the interactive neurotoxic effects of both HIV and tobacco smoking. Evidence suggests that smoking and HIV can have synergistic effects on neurotoxicity and NCI in PWH. Some mechanisms for neurotoxicity include increased oxidative stress from microglial activation and dysfunction in the alpha7- nAChR cholinergic anti-inflammatory pathway leading to increased neuroinflammation and neuronal apoptosis. Mechanisms may vary by cell type and brain region, however, and there is a need for more human-facing, longitudinal studies on smoking in PWH.https://doi.org/10.1186/s12981-025-00714-yHIVTobacco smokingNeurocognitive impairmentnAChRNeuroinflammationNicotine
spellingShingle Benjamin L. Orlinick
Shelli F. Farhadian
HIV, smoking, and the brain: a convergence of neurotoxicities
AIDS Research and Therapy
HIV
Tobacco smoking
Neurocognitive impairment
nAChR
Neuroinflammation
Nicotine
title HIV, smoking, and the brain: a convergence of neurotoxicities
title_full HIV, smoking, and the brain: a convergence of neurotoxicities
title_fullStr HIV, smoking, and the brain: a convergence of neurotoxicities
title_full_unstemmed HIV, smoking, and the brain: a convergence of neurotoxicities
title_short HIV, smoking, and the brain: a convergence of neurotoxicities
title_sort hiv smoking and the brain a convergence of neurotoxicities
topic HIV
Tobacco smoking
Neurocognitive impairment
nAChR
Neuroinflammation
Nicotine
url https://doi.org/10.1186/s12981-025-00714-y
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