The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH

Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially...

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Main Authors: Mayara Sabino Leite de Oliveira Duarte, Wlisses Henrique Veloso de Carvalho-Silva, Rafael Lima Guimarães
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/7/884
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author Mayara Sabino Leite de Oliveira Duarte
Wlisses Henrique Veloso de Carvalho-Silva
Rafael Lima Guimarães
author_facet Mayara Sabino Leite de Oliveira Duarte
Wlisses Henrique Veloso de Carvalho-Silva
Rafael Lima Guimarães
author_sort Mayara Sabino Leite de Oliveira Duarte
collection DOAJ
description Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15–30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target.
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spelling doaj-art-acafcc0c7c30400dbd71eea66698596e2025-08-20T03:32:19ZengMDPI AGViruses1999-49152025-06-0117788410.3390/v17070884The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWHMayara Sabino Leite de Oliveira Duarte0Wlisses Henrique Veloso de Carvalho-Silva1Rafael Lima Guimarães2Department of Genetics, Federal University of Pernambuco (UFPE), Recife 50670-901, Pernambuco, BrazilDepartment of Immunology, Aggeu Magalhães Institute (IAM/FIOCRUZ), Recife 50670-420, Pernambuco, BrazilDepartment of Genetics, Federal University of Pernambuco (UFPE), Recife 50670-901, Pernambuco, BrazilHuman immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15–30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target.https://www.mdpi.com/1999-4915/17/7/884antiretroviral therapyimmunological non-respondersCD4+ T lymphocytesprogrammed cell deathpyroptosis
spellingShingle Mayara Sabino Leite de Oliveira Duarte
Wlisses Henrique Veloso de Carvalho-Silva
Rafael Lima Guimarães
The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
Viruses
antiretroviral therapy
immunological non-responders
CD4+ T lymphocytes
programmed cell death
pyroptosis
title The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
title_full The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
title_fullStr The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
title_full_unstemmed The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
title_short The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH
title_sort role of autophagy in hiv infection and immunological recovery of art treated plwh
topic antiretroviral therapy
immunological non-responders
CD4+ T lymphocytes
programmed cell death
pyroptosis
url https://www.mdpi.com/1999-4915/17/7/884
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