{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:12:23Z","timestamp":1788459143166,"version":"build-2803163510"},"reference-count":97,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VAMC-CT"},{"name":"Ruth and Fred Kunnes Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The C-C chemokine receptor type 5 (CCR5) is the principal co-receptor for R5-tropic HIV-1 and remains one of the most promising therapeutic targets in the pursuit of an HIV cure. The discovery that individuals carrying the naturally occurring CCR5\u039432 mutation exhibit marked resistance to HIV infection established the foundation for both genetic and pharmacological approaches to CCR5 inhibition. This review summarizes recent advances in CCR5-targeted therapies with a focus on CRISPR\/Cas9-mediated gene editing and maraviroc-mediated receptor blockade. We discuss the molecular mechanisms, preclinical evidence and emerging clinical data supporting CRISPR-based CCR5 disruption, including multiplex editing strategies designed to overcome viral tropism switching. We also examine the evolving role of maraviroc beyond viral entry inhibition, highlighting its immunomodulatory effects, potential latency-reversing activity and applications in graft-versus-host disease and cancer. Together, these complementary strategies underscore the potential of CCR5-targeted interventions as integral components of future combination therapies aimed at achieving durable HIV remission or functional cure.<\/jats:p>","DOI":"10.3390\/v18090972","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:13:25Z","timestamp":1788455605000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CCR5 as a Therapeutic Target in HIV Disease: From CRISPR\/Cas9 Gene Editing to Maraviroc-Mediated Inhibition"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2341-0974","authenticated-orcid":false,"given":"Uzair","family":"Iqbal","sequence":"first","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8333-6747","authenticated-orcid":false,"given":"Khadija","family":"Khalid","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8253-530X","authenticated-orcid":false,"given":"Mohamed","family":"Shaltout","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus","family":"Yukselten","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, J.W., Liu, J.H., and Xun, J.J. 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