The interconnection between periodontitis and HIV-1 latency: Molecular mechanisms and therapeutic insights

Periodontitis is one of the major global public health problems associated with the occurrence and development of diverse systemic diseases, especially acquired immune deficiency syndrome (AIDS), necessitating further research and clinical attention. The persistence of HIV-1 latency poses a significant challenge to the attainment of a functional cure for AIDS, despite the introduction of highly active antiretroviral therapy (HAART). A similar mechanistic basis between periodontitis and HIV-1 latency has been revealed by many studies, suggesting possible mechanisms whereby periodontitis and HIV-1 latency may mutually influence each other. Therefore, we aimed to systematically summarize the current research on periodontitis and HIV-1 latency to investigate their potential correlations. This study revealed several common hubs for periodontitis and HIV-1 latency in the nuclear factor kappa-B (NF-κB) signaling pathway and other signaling pathways, including the Wnt/β-catenin pathway, bromodomain-containing protein 4 (BRD4), protein kinase C (PKC), the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, programmed cell death protein 1 (PD-1), histone deacetylases (HDACs), and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Furthermore, we will discuss the hypothesis that periodontal pathogens may represent the unifying mechanism elucidating the intricate interconnection between periodontitis and HIV-1 latency. This article presents a detailed and comprehensive overview of the relationship underlying periodontitis and HIV-1 latency in terms of molecular mechanisms, which may provide novel theoretical insight into the pathogenesis of periodontitis and HIV-1 latency and reveal suitable therapeutic targets for the two diseases.