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Heavily treatment-experienced (HTE) people with HIV (PWH) are limited to two or fewer available fully active ARV classes and are more likely to have an AIDS-defining event. Appropriate identification and management of HTE PWH is crucial to improving patient outcomes and reducing the future spread of drug-resistant HIV. As treatment options become more limited owing to drug resistance, the availability of more potent drugs with a marked increase in virologic suppression is needed in the current ART era. The purpose of this narrative review is to review the identification of HTE PWH, novel mechanisms of resistance, and management of HTE PWH in resource-rich and resource-limited settings using novel ARVs and combination ART.<\/jats:p>","DOI":"10.1177\/03000605241301883","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T05:10:37Z","timestamp":1733375437000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Heavily treatment-experienced patients with HIV: are new mechanisms of action enough?"],"prefix":"10.1177","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6986-2042","authenticated-orcid":false,"given":"Marisa B.","family":"Brizzi","sequence":"first","affiliation":[{"name":"HIV Clinical Pharmacy Specialist, Department of Pharmacy, University of Cincinnati Health, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Cable","sequence":"additional","affiliation":[{"name":"Assistant Professor of Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimple C.","family":"Patel","sequence":"additional","affiliation":[{"name":"HIV Clinical Pharmacy Specialist, Department of Pharmacy, University of Cincinnati Health, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Williams","sequence":"additional","affiliation":[{"name":"Associate Professor of Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9985-0693","authenticated-orcid":false,"given":"Zoe","family":"Adjei","sequence":"additional","affiliation":[{"name":"PGY-2 Ambulatory Pharmacy Resident, Department of Pharmacy, University of Cincinnati Health, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Fichtenbaum","sequence":"additional","affiliation":[{"name":"Professor of Clinical Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"bibr1-03000605241301883","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04161-5"},{"key":"bibr2-03000605241301883","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371101"},{"key":"bibr3-03000605241301883","doi-asserted-by":"publisher","DOI":"10.7573\/dic.2021-9-1"},{"key":"bibr4-03000605241301883","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000002679"},{"key":"bibr5-03000605241301883","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002635"},{"key":"bibr6-03000605241301883","unstructured":"HIV drug resistance: brief report 2024. 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