The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice

Antiretroviral therapy (ART) has significantly improved the prognosis of human immunodeficiency virus type 1 (HIV-1) infection. Although ART can suppress plasma viraemia below detectable levels, it cannot eradicate the HIV-1 DNA (provirus) integrated into the host cell genome. This integration often results in unrepaired DNA damage due to HIV-induced inhibition of DNA repair pathways. Furthermore, HIV in-fection causes telomere attrition in host chromosomes, a critical factor contributing to CD4+ T-cell senescence and apoptosis. HIV proteins can induce DNA damage, block DNA replication, and activate DNA damage responses across various organs. In this review, we explore multiple aspects of the intricate interactions between HIV-1 and the host genome involved in CD4+ T-cell depletion, inflammaging, clonal expansion of infected cells in long-term treated patients, and viral latency. We discuss the molecular mechanisms of DNA damage that contribute to comorbidities in HIV-1-infected individuals and highlight emerging therapeutic strategies targeting the integrated HIV provirus.