{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:01:55Z","timestamp":1791511315875,"version":"4.3.4"},"reference-count":431,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01 MH110360"],"award-info":[{"award-number":["R01 MH110360"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIMH Comprehensive NeuroHIV Center","award":["P30 MH092177"],"award-info":[{"award-number":["P30 MH092177"]}]},{"name":"Ruth L. Kirschstein National Research Service Award","award":["T32 MH079785"],"award-info":[{"award-number":["T32 MH079785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell\u2019s DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. \u201cShock and Kill\u201d uses latency reversal agents to open the provirus\u2019s chromatin, promoting high levels of gene expression that induce the killing of infected cells. \u201cBlock and Lock\u201d uses latency promoting agents to induce heterochromatin, blocking transcription and forcing HIV-1 into a state of deep latency. Here, the compounds investigated in both strategies are reviewed, including their chemical structures, mechanisms of action, and clinical results. Finally, the use of CRISPR-Cas therapeutics and the impact of chromatin architecture on its efficacy are discussed.<\/jats:p>","DOI":"10.3390\/v18030354","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:26:19Z","timestamp":1773390379000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Breaking into HIV-1\u2019s Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5420-1214","authenticated-orcid":false,"given":"Joanna E.","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea E.","family":"Gunderson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-0936","authenticated-orcid":false,"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Nonnemacher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Molecular Virology and Gene Therapy, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2025, September 24). 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