{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:58:53Z","timestamp":1790456333852,"version":"4.1.0"},"reference-count":225,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antiretroviral therapy (ART) has significantly improved the prognosis of human immunodeficiency virus type 1 (HIV-1) infection. Although ART can suppress plasma viremia 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 the HIV-1-induced inhibition of DNA repair pathways. Furthermore, HIV-1 infection causes telomere attrition in host chromosomes, a critical factor contributing to CD4+ T cell senescence and apoptosis. HIV-1 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, the 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-1 provirus.<\/jats:p>","DOI":"10.3390\/ijms26073184","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice"],"prefix":"10.3390","volume":"26","author":[{"given":"Manlio","family":"Tolomeo","sequence":"first","affiliation":[{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Infectious Diseases, (Azienda Ospedaliera Universitaria Policlinico) A.O.U.P. Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Tolomeo","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-1796","authenticated-orcid":false,"given":"Antonio","family":"Cascio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Infectious Diseases, (Azienda Ospedaliera Universitaria Policlinico) A.O.U.P. Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3390\/v14010054","article-title":"Structural Analysis of Retrovirus Assembly and Maturation","volume":"14","author":"Krebs","year":"2021","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41579-021-00586-9","article-title":"Structure and function of retroviral integrase","volume":"20","author":"Maertens","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4331\/wjbc.v8.i1.32","article-title":"Retroviral integrase protein and intasome nucleoprotein complex structures","volume":"8","author":"Grawenhoff","year":"2017","journal-title":"World J. Biol. 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