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

TL;DR

This paper reviews how autophagy, a cellular process, affects immune recovery in HIV patients on antiretroviral therapy.

Contribution

The paper highlights autophagy's role in immune recovery and its potential as a therapeutic target for HIV patients.

Findings

Autophagy modulates CD4+ T cell survival and immune recovery in HIV patients.

Impaired autophagy may contribute to immunological non-response in ART-treated individuals.

Autophagy interacts with cell death pathways like apoptosis and necroptosis in HIV progression.

Abstract

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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