{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:16:34Z","timestamp":1783707394698,"version":"3.55.0"},"reference-count":162,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015498","name":"Innov\u00e1ci\u00f3s \u00e9s Technol\u00f3giai Miniszt\u00e9rium","doi-asserted-by":"publisher","award":["TKP2021-EGA-20"],"award-info":[{"award-number":["TKP2021-EGA-20"]}],"id":[{"id":"10.13039\/501100015498","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015498","name":"Innov\u00e1ci\u00f3s \u00e9s Technol\u00f3giai Miniszt\u00e9rium","doi-asserted-by":"publisher","award":["EK\u00d6P-24-4-I-DE-435"],"award-info":[{"award-number":["EK\u00d6P-24-4-I-DE-435"]}],"id":[{"id":"10.13039\/501100015498","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian Academy of Science","award":["BO\/00110\/23\/5"],"award-info":[{"award-number":["BO\/00110\/23\/5"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The capsid (CA) of the human immunodeficiency virus (HIV) has emerged as a critical therapeutic target owing to its essential roles in viral replication, nuclear import, and integration. Capsid inhibitors (CIs) disrupt these processes by binding to highly conserved structural interfaces, offering a novel mechanism distinct from enzyme-targeting antiretrovirals. In this review, we summarize the molecular architecture of the HIV-1 CA and its interactions with host factors, and we compare key structural and functional differences between HIV-1 and HIV-2. We provide an overview of established and investigational CIs, explore the resistance-associated mutations, their structural basis, and their impact on inhibitor potency, alongside insights into cross-resistance patterns. Special emphasis is placed on lenacapavir, exploring data from pivotal trials and emerging applications in both treatment and prevention, including long-acting pre-exposure prophylaxis (PrEP). Moreover, we highlight future perspectives, including the need for global surveillance of CA polymorphisms, strategies to overcome resistance, and challenges in accessibility and cost-effectiveness in resource-limited settings. Collectively, CIs represent a transformative addition to the HIV therapeutic arsenal, though their optimal deployment requires careful consideration of efficacy, resistance, and implementation barriers.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014361","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:49:41Z","timestamp":1783705781000},"page":"e1014361","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-5996","authenticated-orcid":true,"given":"Mohamed","family":"Mahdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Botond","family":"Lakatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos Andr\u00e1s","family":"M\u00f3ty\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyula","family":"Hoffka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"T\u0151zs\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ppat.1014361.ref001","author":"World Health Organization."},{"key":"ppat.1014361.ref002","article-title":"Global, regional, and national burden of hiv\/aids, 1990-2021, and forecasts to 2050, for 204 countries and territories: The global burden of disease study 2021","volume":"11","author":"GH Collaborators","year":"2024","journal-title":"The Lancet HIV"},{"key":"ppat.1014361.ref003","volume-title":"Retroviruses","author":"JM 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