Unveiling the Molecular Mechanisms of Erythropoietin in HIV Pathogenesis: A Review

Abstract

Erythropoietin is a glycoprotein hormone traditionally recognized for its central role in regulating erythropoiesis. Increasing evidence, however, highlights its pleiotropic effects in immunity, inflammation, and cellular protection, which are particularly relevant in the pathogenesis of human immunodeficiency virus infection. Anemia remains one of the most common complications of HIV and is often linked to impaired EPO production or resistance to EPO signaling, exacerbated by chronic inflammation and viral-induced bone marrow suppression. Beyond hematopoiesis, EPO modulates immune responses, attenuates oxidative stress, and exerts anti-apoptotic effects through key pathways such as JAK2/STAT5, PI3K/Akt, and MAPK. These mechanisms may mitigate immune cell loss and tissue damage but can also inadvertently support viral persistence by protecting infected cells. Recombinant human EPO has shown clinical benefits in correcting HIV-associated anemia, yet its broader therapeutic implications and potential as a biomarker remain insufficiently explored. This review examines the molecular mechanisms by which EPO influences HIV pathogenesis, integrating insights into hematopoietic dysfunction, immune modulation, oxidative stress, apoptosis, and viral dynamics. A deeper understanding of these mechanisms could expand the therapeutic landscape of HIV care, positioning EPO as both a treatment adjunct and a marker of disease progression.