{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T06:38:18Z","timestamp":1780814298959,"version":"3.54.1"},"reference-count":15,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["R37 AI076119"],"award-info":[{"award-number":["R37 AI076119"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["R01 AI148382"],"award-info":[{"award-number":["R01 AI148382"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["P30 AI050409"],"award-info":[{"award-number":["P30 AI050409"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["U54 AI150472"],"award-info":[{"award-number":["U54 AI150472"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["R01 AI120860"],"award-info":[{"award-number":["R01 AI120860"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["F31 AI155158-01A1"],"award-info":[{"award-number":["F31 AI155158-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["T32 GM008367"],"award-info":[{"award-number":["T32 GM008367"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["R37 AI076119"],"award-info":[{"award-number":["R37 AI076119"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["R01 AI148382"],"award-info":[{"award-number":["R01 AI148382"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["P30 AI050409"],"award-info":[{"award-number":["P30 AI050409"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["U54 AI150472"],"award-info":[{"award-number":["U54 AI150472"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["R01 AI120860"],"award-info":[{"award-number":["R01 AI120860"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["F31 AI155158-01A1"],"award-info":[{"award-number":["F31 AI155158-01A1"]}]},{"name":"Nahmias-Schinazi Distinguished Chair","award":["T32 GM008367"],"award-info":[{"award-number":["T32 GM008367"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Long-acting (LA) anti-HIV regimens show promise for increasing dosing intervals and consequently, improving the patients\u2019 quality of life. The first FDA-approved LA therapy is Cabenuva, which comprises rilpivirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (integrase strand transfer inhibitor). Novel promising LA anti-HIV agents such as lenacapavir (a capsid-targeting antiviral) and islatravir (EFdA, a nucleoside reverse transcriptase translocation inhibitor) need to be explored as combination therapies. Therefore, we sought to determine whether combination of lenacapavir with islatravir, rilpivirine, or cabotegravir displayed synergy, additivity, or antagonism. We performed dose-response matrices of these drug combinations in an HIV-1 reporter cell line and subsequently analyzed the data with SynergyFinder Plus, which employs four major drug interaction models: highest single agent, Bliss independence, Loewe additivity, and zero interaction potency. Most of these models predict additive inhibition by the studied drug combinations This work highlights the importance of effective drug combinations in LA-regimens.<\/jats:p>","DOI":"10.3390\/v14061202","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T21:43:42Z","timestamp":1654119822000},"page":"1202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Drug Interactions in Lenacapavir-Based Long-Acting Antiviral Combinations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7597-1248","authenticated-orcid":false,"given":"Maria E.","family":"Cilento","sequence":"first","affiliation":[{"name":"Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Tsuey","family":"Ong","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-4967","authenticated-orcid":false,"given":"Philip R.","family":"Tedbury","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan G.","family":"Sarafianos","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","unstructured":"(2022, March 20). UNIAIDS, Global HIV & AIDS Statistics\u2014Fact Sheet. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/jama.2018.1917","article-title":"HIV Preexposure Prophylaxis: A Review","volume":"319","author":"Riddell","year":"2018","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/1871526517666170505122800","article-title":"HAART in HIV\/AIDS Treatments: Future Trends","volume":"18","author":"Lu","year":"2018","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_4","unstructured":"Eggleton, J.S., and Nagalli, S. (2021). Highly Active Antiretroviral Therapy (HAART). StatPearls, Treasure Island (FL), StatPearls Publishing LLC."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s40265-020-01326-8","article-title":"Cabotegravir Plus Rilpivirine: First Approval","volume":"80","author":"Markham","year":"2020","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/QCO.0000000000000701","article-title":"Long-acting injectable HIV therapies: The next frontier","volume":"34","author":"Thornhill","year":"2021","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/COH.0000000000000467","article-title":"4\u2032-Ethynyl-2-fluoro-2\u2032-deoxyadenosine, MK-8591: A novel HIV-1 reverse transcriptase translocation inhibitor","volume":"13","author":"Markowitz","year":"2018","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8392","DOI":"10.1073\/pnas.90.18.8392","article-title":"Production of high-titer helper-free retroviruses by transient transfection","volume":"90","author":"Pear","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12585","DOI":"10.1128\/JVI.01726-08","article-title":"Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research","volume":"82","author":"Takeuchi","year":"2008","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zheng, S., Wang, W., Aldahdooh, J., Malyutina, A., Shadbahr, T., Tanoli, Z., Pessia, A., and Tang, J. (2022). SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets. Genom. Proteom. Bioinform.","DOI":"10.1101\/2021.06.01.446564"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Malyutina, A., Majumder, M.M., Wang, W., Pessia, A., Heckman, C.A., and Tang, J. (2019). Drug combination sensitivity scoring facilitates the discovery of synergistic and efficacious drug combinations in cancer. PLoS Comput. Biol., 15.","DOI":"10.1101\/512244"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.csbj.2015.09.001","article-title":"Searching for Drug Synergy in Complex Dose-Response Landscapes Using an Interaction Potency Model","volume":"13","author":"Yadav","year":"2015","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1744-7348.1939.tb06990.x","article-title":"The toxicity of poisons applied jointly","volume":"26","author":"Bliss","year":"1939","journal-title":"Ann. Appl. Biol."},{"key":"ref_14","first-page":"285","article-title":"The problem of synergism and antagonism of combined drugs","volume":"3","author":"Loewe","year":"1953","journal-title":"Arzneimittelforschung"},{"key":"ref_15","first-page":"93","article-title":"What is synergy?","volume":"41","author":"Berenbaum","year":"1989","journal-title":"Pharmacol. Rev."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:02Z","timestamp":1760138582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":15,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["v14061202"],"URL":"https:\/\/doi.org\/10.3390\/v14061202","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,31]]}}}