{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:47:48Z","timestamp":1791920868878,"version":"4.3.4"},"reference-count":91,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    The mainstay of antiretroviral therapy (ART) has been combination oral therapy. While oral ART is highly effective, nonadherence remains a chief concern. Addressing this concern in recent years is the emergence of long\u2010acting antiretrovirals for the treatment and prevention of HIV\u20101 infection. The most recently approved long\u2010acting antiretroviral is the first\u2010in\u2010class capsid inhibitor lenacapavir (LEN) for heavily treatment\u2010experienced adults with multidrug\u2010resistant HIV\u20101 infection. Due to its biannual subcutaneous dosing scheme to inhibit the HIV\u20101 capsid, LEN exhibits unique pharmacokinetics and reinforces an evolving era of ART. In this review, we evaluate published and accepted research articles, conference proceedings, and clinical trial records to provide a comprehensive overview of LEN for treatment and preliminary data for the prevention of HIV\u20101 infection. These data include clinical trials outcomes,\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    resistance profiles, and preclinical data supporting downstream indications. We also discuss the unique clinical pharmacology of LEN with the goal of serving as a resource toward subsequent physiologically based, population\u2010based, and other miscellaneous pharmacometric\u2010focused analyses. Given the dynamic nature of the HIV treatment and prevention research fields, we also discuss ongoing studies related to LEN for treatment\u2010na\u00efve adults and for prevention. Lastly, we discuss important pharmacologic gaps in special populations, drug\u2013drug interactions, and at the sites of action germane to HIV treatment and prevention. The information discussed in this review will provide knowledge and understanding of the unique pharmacologic properties of LEN to assist clinicians and researchers as they navigate the dynamic HIV research landscape.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3447","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:40:58Z","timestamp":1727311258000},"page":"353-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lenacapavir: Playing the Long Game in the New Era of Antiretrovirals"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0372-2924","authenticated-orcid":false,"given":"Noah C.","family":"Neverette","sequence":"first","affiliation":[{"name":"Center for Clinical Pharmaceutical Sciences, Department of Pharmacy &amp; Therapeutics, School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-5819","authenticated-orcid":false,"given":"Julie B.","family":"Dumond","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-3539","authenticated-orcid":false,"given":"Deborah K.","family":"McMahon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2778-3725","authenticated-orcid":false,"given":"Aaron S.","family":"Devanathan","sequence":"additional","affiliation":[{"name":"Center for Clinical Pharmaceutical Sciences, Department of Pharmacy &amp; Therapeutics, School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"e_1_2_13_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(22)00063-0"},{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506816"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002142"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-011-9942-x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-021-01883-8"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/apc.2009.0309"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/378301"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03391-y"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114862"},{"key":"e_1_2_13_10_1","unstructured":"Gilead Sciences Prescribing information for lenacapavir injection (Sunleca) [Package Insert](2022)."},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3503"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb785"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.02.008"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001220"},{"key":"e_1_2_13_15_1","first-page":"100","article-title":"Structure, function, and interactions of the HIV\u20101 capsid protein","volume":"11","author":"Rossi E.","year":"2021","journal-title":"Life (Basel)"},{"key":"e_1_2_13_16_1","unstructured":"Li C. Burdick R.C.&Hu W.S.Lenacapavir Disrupts HIV\u20101 Core Integrity While Stabilizing the Capsid Lattice. (Abstract 215).Conference on Retroviruses and Opportunistic Infections(2023)."},{"key":"e_1_2_13_17_1","first-page":"383","article-title":"A molecular switch modulates assembly and host factor binding of the HIV\u20101 capsid","volume":"30","author":"Schirra R.T.","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2443-1"},{"key":"e_1_2_13_19_1","unstructured":"NIH Lenacapavir Chemical and Physical Properties.PubChemhttps:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Lenacapavir#section=Depositor\u2010Supplied\u2010Synonyms."},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-023-00864-9"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182986ff8"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjaceaccp\/mkr018"},{"key":"e_1_2_13_23_1","unstructured":"VanderVeen L.Activity and Resistance Characterization of the HIV Capsid Inhibitor Lenacapavir. (Abstract 128).Conference on Retroviruses and Opportunistic Infections(2021)."},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad562"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02057-20"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01804-22"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab503"},{"key":"e_1_2_13_28_1","unstructured":"Sager J.Safety and PK of Subcutaneous GS\u20106207 A Novel HIV\u20101 Capsid Inhibitor. (Abstract 141).Conference on Retroviruses and Opportunistic Infections(2019)."},{"key":"e_1_2_13_29_1","unstructured":"Daar E.Dose\u2010response Relationship of Subcutaneous Long\u2010acting HIV Capsid Inhibitor. (Abstract 469).Conference on Retroviruses and Opportunistic Infections(2020)."},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(22)00291-0"},{"key":"e_1_2_13_31_1","unstructured":"Hagins D.P.et al.Long\u2010Acting Lenacapavir in a Combination Regimen for Treatment Naive PWH: Week 80. (Abstract 522).Conference on Retroviruses and Opportunistic Infections(2023)."},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(22)00375-7"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2115542"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00113-3"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac364"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad500.1431"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa060"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac388"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae115"},{"key":"e_1_2_13_40_1","unstructured":"Hingrat Q.L.Rapid Selection of HIV\u20102 Capsid Mutations After Failure of a Lenacapavir\u2010Containing Regimen. (Abstract 682).Conference on Retroviruses and Opportunistic Infections(2024)."},{"key":"e_1_2_13_41_1","unstructured":"Ogbuagu O.CAPELLA: Wk 104 results with long\u2010acting subcutaneous Lenacapavir in persons living with multidrug\u2010resistant HIV. IDWeek(2023)."},{"key":"e_1_2_13_42_1","unstructured":"NDA 215973\/215974.Sunlenca [FDA Integrated Review](2022)."},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01328-1"},{"key":"e_1_2_13_44_1","unstructured":"Gilead Sciences Study of Lenacapavir and Emtricitabine\/Tenofovir Disoproxil Fumarate (F\/TDF) in Prevention of HIV in Cisgender Women in the United States (HPTN\u2010102) (PURPOSE 3).ClinicalTrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT06101329?intr=Lenacapavir&rank=4> (2024)."},{"key":"e_1_2_13_45_1","unstructured":"Gilead Sciences Study of Lenacapavir and Emtricitabine\/Tenofovir Disoproxil Fumarate (F\/TDF) for Prevention of HIV in People Who Inject Drugs (HPTN\u2010103) (PURPOSE\u20104).Clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT06101342?intr=Lenacapavir&rank=5#publications> (2024)."},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00626"},{"key":"e_1_2_13_47_1","unstructured":"Jogiraju V.Pharmacokinetics of a Simplified Subcutaneous Lenacapavir Regimen Versus Phase 2\/3 Regimen. (Poster PESUB22).International AIDS Conference(2022)."},{"key":"e_1_2_13_48_1","unstructured":"Shaik N.et al.Comparison of Long\u2010Acting Lenacapavir Phase 2\/3 Regimen vs Simplified Regimen Using Population\u2010PK Analysis and Simulation. (Poster EPB0230).International AIDS Society Conference(2023)."},{"key":"e_1_2_13_49_1","unstructured":"Shaik N.A.et al.Population PK Analysis to Guide Dosing Window Following Lenacapavir SC Administration. (Abstract 504).Conference on Retroviruses and Opportunistic Infections(2023)."},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00293-X"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01344-23"},{"key":"e_1_2_13_52_1","unstructured":"Eron J.J.Lenacapavir Plus bNAbs for People With HIV and Sensitivity to Either Teropavimab or Zinlirvimab. (Abstract 120).Conference on Retroviruses and Opportunistic Infections<https:\/\/www.croiconference.org\/abstract\/lenacapavir\u2010plus\u2010bnabs\u2010for\u2010people\u2010with\u2010hiv\u2010and\u2010sensitivity\u2010to\u2010either\u2010teropavimab\u2010or\u2010zinlirvimab\/> (2024)."},{"key":"e_1_2_13_53_1","unstructured":"Gilead Sciences Study to Compare Bictegravir\/Lenacapavir Versus Current Therapy in People With HIV\u20101 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY\u20101).clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT05502341?intr=Lenacapavir&page=1&rank=9> (2024)."},{"key":"e_1_2_13_54_1","unstructured":"Mounzer K.Phase 2 Study of Switch to Daily BIC + LEN in Individuals on a Complex HIV Treatment Regimen. (Abstract 642).Conference on Retroviruses and Opportunistic Infections(2024)."},{"key":"e_1_2_13_55_1","unstructured":"Gilead Sciences Study to Compare Bictegravir\/Lenacapavir Versus Current Therapy in People With HIV\u20101 Who Are Successfully Treated With Biktarvy (ARTISTRY\u20102).clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT06333808?term=ARTISTRY\u20102&rank=1> (2024)."},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae125"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000467"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_2_13_59_1","unstructured":"Diamond T.L.et al.No Antagonism or Cross\u2010Resistance Observed Between Islatravir and Lenacapavir. (Abstract 585).Conference on Retroviruses and Opportunistic Infections(2023)."},{"key":"e_1_2_13_60_1","unstructured":"Gilead Sciences Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV.clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT05052996?intr=Lenacapavir&page=2&rank=12> (2023)."},{"key":"e_1_2_13_61_1","unstructured":"Colson A.Efficacy and Safety of Weekly Islatravir Plus Lenacapavir in PWH at 24\u2009Weeks: A Phase II Study. (Abstract 208).Conference on Retroviruses and Opportunistic Infections(2024)."},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108524"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25408"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2020.1783233"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab152"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00538-4"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI167818"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104764"},{"key":"e_1_2_13_69_1","doi-asserted-by":"crossref","unstructured":"Gilead Sciences Pre\u2010Exposure Prophylaxis Study of Lenacapavir and Emtricitabine\/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1).ClinicalTrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT04994509?intr=Lenacapavir&rank=10> (2024).","DOI":"10.1007\/s40278-024-66078-x"},{"key":"e_1_2_13_70_1","unstructured":"Gilead Sciences Study of Lenacapavir for HIV Pre\u2010Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2).ClinicalTrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT04925752?intr=Lenacapavir&page=2&rank=11> (2023)."},{"key":"e_1_2_13_71_1","unstructured":"Ross J.&Smith M.Gilead Sciences Announces New Clinical Trial in Europe to Assess Lenacapavir for HIV Prevention as Part of Landmark Purpose Program.Gilead<https:\/\/www.gilead.com\/news\u2010and\u2010press\/press\u2010room\/press\u2010releases\/2023\/10\/gilead\u2010sciences\u2010announces\u2010new\u2010clinical\u2010trial\u2010in\u2010europe\u2010to\u2010assess\u2010lenacapavir\u2010for\u2010hiv\u2010prevention\u2010as\u2010part\u2010of\u2010landmark\u2010purpose\u2010program> (2023)."},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2407001"},{"key":"e_1_2_13_73_1","unstructured":"Gilead Sciences Inc.Gilead's Twice\u2010Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada\u00ae for HIV Prevention.Gilead<https:\/\/www.gilead.com\/news\u2010and\u2010press\/press\u2010room\/press\u2010releases\/2024\/6\/gileads\u2010twiceyearly\u2010lenacapavir\u2010demonstrated\u2010100\u2010efficacy\u2010and\u2010superiority\u2010to\u2010daily\u2010truvada\u2010for\u2010hiv\u2010prevention> (2024)."},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semperi.2020.151221"},{"key":"e_1_2_13_75_1","volume-title":"In Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach: 2010 Revision","author":"World Health Organization Considerations for ART in Adolescents","year":"2010"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/jppr.1373"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530902722679"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-43099-7_10"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000003973"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0148-z"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2004.05.010"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1270"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.08.013"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0432"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4411"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134815"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1027682"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003831"},{"key":"e_1_2_13_89_1","unstructured":"Lenacapavir predicted properties.Drug Bank<https:\/\/go.drugbank.com\/drugs\/DB15673> (2023)."},{"key":"e_1_2_13_90_1","unstructured":"Gilead Sciences A Study of GS\u20105423 and GS\u20102872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV\u20101 Infection.clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT05729568?intr=Lenacapavir&page=1&rank=2#publications> (2024)."},{"key":"e_1_2_13_91_1","unstructured":"Gilead Sciences Study of Lenacapavir Taken Twice a Year for HIV Pre\u2010Exposure Prophylaxis (PrEP) (PURPOSE 5).Clinicaltrials.gov<https:\/\/clinicaltrials.gov\/study\/NCT06513312?intr=Lenacapavir&term=PURPOSE&rank=1> (2024)."}],"updated-by":[{"DOI":"10.1002\/cpt.3647","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T00:00:00Z","timestamp":1742083200000}}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T02:44:21Z","timestamp":1737081861000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,25]]},"references-count":91,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/cpt.3447"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3447","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,25]]},"assertion":[{"value":"2024-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}