CD4+ T Cell Exhaustion Biomarkers in Chronic HIV Infection: Prognostic Implications

Mangen Joshua Fred

Department of Pharmacy Kampala International University Uganda

Email: mangenjoshuafred@gmail.com

ABSTRACT

Chronic human immunodeficiency virus (HIV) infection was characterized by progressive immune dysfunction, in which CD4+ T cell depletion and exhaustion play pivotal roles. CD4+ T cell exhaustion, marked by impaired proliferative capacity and sustained expression of inhibitory receptors, contributes to poor immune reconstitution despite effective antiretroviral therapy. Biomarkers such as programmed cell death protein 1 (PD-1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte antigen 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3) had been proposed as key indicators of T cell dysfunction, while soluble inflammatory mediators provide complementary prognostic information. The purpose of this review was to critically evaluate the prognostic implications of CD4+ T cell exhaustion biomarkers in chronic HIV infection, focusing on their utility for predicting disease progression, therapeutic outcomes, and comorbid risks. A narrative synthesis was conducted using PubMed, Scopus, and Web of Science databases for studies published between 2012 and 2025, including clinical trials, mechanistic investigations, and translational studies of immune biomarkers in HIV. Evidence indicated that high expression of PD-1 and TIM-3 correlates with accelerated CD4+ decline, higher viral reservoirs, and increased risk of opportunistic infections. Combinatorial biomarker profiling enhanced prognostic accuracy beyond single markers. Importantly, exhaustion biomarkers also predicted responsiveness to immune-based therapies and vaccine strategies. Despite their promise, variability across cohorts and technical limitations hindered standardization. CD4+ T cell exhaustion biomarkers provided valuable insights into HIV pathogenesis and may guide prognostic assessment and therapeutic innovation.

Keywords: HIV, CD4+ T cell, Immune exhaustion, Biomarkers, Prognosis.

CITE AS: Mangen Joshua Fred (2025). CD4+ T Cell Exhaustion Biomarkers in Chronic HIV Infection: Prognostic Implications. IDOSR JOURNAL OF APPLIED SCIENCES 10(2):29-32, 2025. https://doi.org/10.59298/IDOSRJAS/2025/102.2932