• Chrysoula I. Liakou
• Markos Plytas
• Marios Papadakis

Cytotoxic T-Lymphocyte-associated molecule 4 (CTLA-4) is one of the most important immune checkpoint proteins that is involved in crucial T-cell activation and immune homeostasis. Dysregulation of the expression of CTLA-4 in the setting of human immunodeficiency virus (HIV) infection has been substantively linked to immune exhaustion, defective antiviral response, and poor clinical outcome. This is a review of existing evidence about how CTLA-4 regulates immune response at various points of status in HIV disease, such as acute viremia, chronic condition, and through viral suppression caused by antiretroviral therapy (ART). The overview relies on research that characterizes the expression of CTLA-4 on HIV-specific CD4+ and CD8+ T cells, its interaction with other inhibitory receptors, including programmed cell death protein 1 (PD-1) and B-and T-lymphocyte attenuator (BTLA), as well as downstream immunoregulatory pathways that determine cytokine production and viral persistence, among others. In addition, we evaluate the effects of therapeutically targeting modulation of CTLA-4, such as checkpoint blockade approaches, on restoration of immune capacity and dynamics of viral reservoirs, recognizing both potential benefits of immune restoration and the danger of increased viral replication. Their results confirm the role of CTLA-4 as the pivot of HIV pathogenesis and need to include immunotherapeutic agents that compromise immune activation and contain viral replication. Relevant future studies need to focus on more longitudinal trials and translational clinical trials to clarify the safety and efficacy of the targeted treatment with CTLA-4 in humans with HIV.

ctla-4; immune regulation; hiv infection; t cell exhaustion; immune checkpoints; disease progression; antiretroviral therapy; viral persistence

"THE ROLE OF CTLA-4 IN IMMUNE REGULATION AND DISEASE PROGRESSION IN HIV INFECTION", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.12, Issue 9, page no.e212-e223, September-2025, Available :http://www.jetir.org/papers/JETIR2509423.pdf

"THE ROLE OF CTLA-4 IN IMMUNE REGULATION AND DISEASE PROGRESSION IN HIV INFECTION", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.12, Issue 9, page no. ppe212-e223, September-2025, Available at : http://www.jetir.org/papers/JETIR2509423.pdf