Unveiling the Role of Extracellular Vesicles in HIV Infection: Molecular Mechanisms, Viral Persistence and Therapeutic Opportunities.

Abstract

Human immunodeficiency virus (HIV) infection remains a major global health challenge despite the success of antiretroviral therapy, largely due to the persistence of viral reservoirs and chronic immune dysregulation. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication during viral infection, operating at the interface between viral and host cellular pathways. Depending on their cellular origin and molecular cargo, EVs can exert context-dependent effects, with studies suggesting roles in both viral dissemination and persistence, as well as in the modulation of antiviral immune responses. This review examines the molecular mechanisms through which EVs have been proposed to contribute to HIV infection, focusing on host-virus interactions, immune regulation, chronic inflammation, and viral latency. We further discuss emerging therapeutic strategies targeting EV biology, including approaches aimed at modulating EV biogenesis and cargo composition, as well as the development of engineered EVs as platforms for drug delivery, gene editing, and immune modulation. Overall, this study highlights the emerging roles of EVs in HIV infection, emphasizing both their potential relevance and the limitations that currently complicate the interpretation of EV-associated effects.