{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:12:22Z","timestamp":1793401942317,"version":"4.5.0"},"reference-count":204,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NHLBI","award":["2R15HL143545-02"],"award-info":[{"award-number":["2R15HL143545-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Despite the success of antiretroviral therapy (ART) in suppressing viral replication in the blood, HIV persists in the central nervous system (CNS) and causes chronic neurocognitive impairment, a hallmark of HIV-associated neurocognitive disorders (HAND). This review looks at the complex interactions among HIV, the blood\u2013brain barrier (BBB), neuroinflammation, and the roles of viral proteins, immune cell trafficking, and pro-inflammatory mediators in establishing and maintaining latent viral reservoirs in the CNS, particularly microglia and astrocytes. Key findings show disruption of the BBB, monocyte infiltration, and activation of CNS-resident cells by HIV proteins like Tat and gp120, contributing to the neuroinflammatory environment and neuronal damage. Advances in epigenetic regulation of latency have identified targets like histone modifications and DNA methylation, and new therapeutic strategies like latency-reversing agents (LRAs), gene editing (CRISPR\/Cas9), and nanoparticle-based drug delivery also offer hope. While we have made significant progress in understanding the molecular basis of HIV persistence in the CNS, overcoming the challenges of BBB penetration and neuroinflammation is key to developing effective therapies. Further research into combination therapies and novel drug delivery systems will help improve outcomes for HAND patients and bring us closer to a functional cure for HIV.<\/jats:p>","DOI":"10.3390\/v17040572","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:05:31Z","timestamp":1744776331000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neuroinflammation, Blood\u2013Brain Barrier, and HIV Reservoirs in the CNS: An In-Depth Exploration of Latency Mechanisms and Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"17","author":[{"given":"Noor","family":"Said","sequence":"first","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":false,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wallet, C., De Rovere, M., Van Assche, J., Daouad, F., De Wit, S., Gautier, V., Mallon, P.W.G., Marcello, A., Van Lint, C., and Rohr, O. 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