Gut microbiota: a novel target for traditional Chinese medicine in the treatment of HIV/AIDS immunological non-responders

Despite effective antiretroviral therapy (ART), many individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) achieve viral suppression but fail to fully restore cluster of differentiation 4 (CD4)⁺ T lymphocyte (CD4 cell) counts—a condition known as immunological non-response (INRs). INRs are associated with elevated health risks, including increased susceptibility to AIDS-related and non-AIDS-related complications. The pathogenesis of INRs remains incompletely understood, and no established therapeutic interventions exist, posing a major challenge in contemporary HIV/AIDS management. Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition. Dysbiosis of the gut microbiota may contribute to persistent immune activation, cytokine imbalance, and cellular pyroptosis, all of which could impair immune reconstitution in people living with HIV/AIDS. Traditional Chinese medicine (TCM) has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs. Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs. This review explores the interplay between gut microbiota and TCM, examines the association between gut dysbiosis and INRs, discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development, and highlights how TCM interventions regulate gut microbiota to promote immune recovery. By focusing on the gut microbiota as a therapeutic interface, this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.