SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity

SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity J. Gerardo Garcia-Lerma, Michele Daly, Chuong Dinh, Angela Holder, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4650825/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Studies in SIV-infected macaques have shown that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posited that optimized ART regimens designed to have robust penetration in tissue reservoirs and provide long-lasting antiviral activity may be advantageous for HIV or SIV remission. Macaques infected with RT-SHIV received oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir and rilpivirine without (n=4) or with (n=4) the immune activator vesatolimod after the initial onset of viremia. All animals were fully suppressed during treatment (4-12 months) and showed no virus rebound during a follow up period of 1.5-2 years despite CD8+ T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a new type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation. Health sciences/Diseases/Infectious diseases/HIV infections Biological sciences/Microbiology/Virology/Retrovirus Full Text Additional Declarations Yes there is potential Competing Interest. JGGL, MD, WH, PW, and WS are named in a US Patent Application (No. 18/002,494) entitled “Methods for achieving viral remission using long-acting antiretroviral agents”. Supplementary Files DalyetalNatCommsupplementarymaterialsFINAL.pdf Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4650825","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":328386849,"identity":"82eb664f-9112-4589-ad37-c4403e32e1ff","order_by":0,"name":"J. Gerardo Garcia-Lerma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAoElEQVRIiWNgGAWjYBACxgYG9g8fGJhJ08LGOIMkLUDAxsxDkhbm2e3XHtvUWMsz8C8+JkGcw+acKTfOOZZu2CDxLI1ILTNyEqRzGw4nMEicMTYgXosliVrSj0kzgrTw9xg+INYWZsMeoF/aJNgSidNiOCP94YMfwBDj5z984ABxWhp4ID5gk0ggSgMDgzwDO9Q5/MTZMQpGwSgYBSMQAABuZC0TQLZ7JAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6437-7745","institution":"Centers for Disease Control and Prevention","correspondingAuthor":true,"prefix":"","firstName":"J.","middleName":"Gerardo","lastName":"Garcia-Lerma","suffix":""},{"id":328386850,"identity":"01246a27-0402-4760-9bf4-8f2b980e988d","order_by":1,"name":"Michele Daly","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Michele","middleName":"","lastName":"Daly","suffix":""},{"id":328386851,"identity":"8c97e430-1495-4317-ad96-f131e825a660","order_by":2,"name":"Chuong Dinh","email":"","orcid":"","institution":"Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA","correspondingAuthor":false,"prefix":"","firstName":"Chuong","middleName":"","lastName":"Dinh","suffix":""},{"id":328386852,"identity":"103954df-57d7-4c52-b661-39398cb1670b","order_by":3,"name":"Angela Holder","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Angela","middleName":"","lastName":"Holder","suffix":""},{"id":328386853,"identity":"1e5a2cef-328d-4872-b5ec-8d2a8a7b7571","order_by":4,"name":"Donna Rudolph","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Donna","middleName":"","lastName":"Rudolph","suffix":""},{"id":328386854,"identity":"8f4600f3-b78b-4981-9201-4046ed35b926","order_by":5,"name":"Susan Ruone","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Ruone","suffix":""},{"id":328386855,"identity":"8d8333b7-f30a-4686-bab8-6414860c6a5b","order_by":6,"name":"Alison Swaims-Kohlmeier","email":"","orcid":"","institution":"Emory University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Alison","middleName":"","lastName":"Swaims-Kohlmeier","suffix":""},{"id":328386856,"identity":"d0cb940b-47a5-4728-a60c-efd4a8311ad2","order_by":7,"name":"George Khalil","email":"","orcid":"","institution":"Quantitative Sciences and Data Management Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Khalil","suffix":""},{"id":328386857,"identity":"5bc3b513-9dd0-47e9-b535-e5122a287017","order_by":8,"name":"Sunita Sharma","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Sunita","middleName":"","lastName":"Sharma","suffix":""},{"id":328386858,"identity":"ff0df20e-254b-474f-a3cf-0d825b401896","order_by":9,"name":"James Mitchell","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"","lastName":"Mitchell","suffix":""},{"id":328386859,"identity":"47d2469e-9475-413b-be4a-676b61339227","order_by":10,"name":"Jillian Condrey","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Jillian","middleName":"","lastName":"Condrey","suffix":""},{"id":328386860,"identity":"f9d3b49e-aaea-4f20-9bde-37087e7d149a","order_by":11,"name":"Daniel Kim","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Kim","suffix":""},{"id":328386861,"identity":"ba1c6362-1dd7-4a7b-ad21-c3a1a6c03bfe","order_by":12,"name":"Yi Pan","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Pan","suffix":""},{"id":328386862,"identity":"876b2833-8a38-4771-900a-0195d5fae0ff","order_by":13,"name":"Kelly Curtis","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Kelly","middleName":"","lastName":"Curtis","suffix":""},{"id":328386863,"identity":"e5ee0149-9c81-457d-8de5-7fdfa5bdc80b","order_by":14,"name":"Peter Williams","email":"","orcid":"","institution":"Janssen Research \u0026 Development","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Williams","suffix":""},{"id":328386864,"identity":"6c55e8ab-441f-4803-8093-d852d9e61a24","order_by":15,"name":"William Spreen","email":"","orcid":"","institution":"ViiV Healthcare (United Kingdom)","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Spreen","suffix":""},{"id":328386865,"identity":"e297f916-7988-4313-82b2-72ad023490ff","order_by":16,"name":"Walid Heneine","email":"","orcid":"","institution":"Centers for Disease Control and Prevention","correspondingAuthor":false,"prefix":"","firstName":"Walid","middleName":"","lastName":"Heneine","suffix":""}],"badges":[],"createdAt":"2024-06-27 20:10:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4650825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4650825/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61458060,"identity":"a26ea7c5-9cdb-44f7-8643-52e012c41066","added_by":"auto","created_at":"2024-07-31 04:01:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1773280,"visible":true,"origin":"","legend":"","description":"","filename":"DalyetalNatureCommmaintextandfiguresFINAL.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4650825/v1_covered_153c7262-06b3-45de-be59-435e66eb0914.pdf"},{"id":61457660,"identity":"9bfd4f2f-ae2f-432c-bd8a-acef902eac58","added_by":"auto","created_at":"2024-07-31 03:53:07","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":325324,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"DalyetalNatCommsupplementarymaterialsFINAL.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4650825/v1/c821af6e732656c6870c5609.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nJGGL, MD, WH, PW, and WS are named in a US Patent Application (No. 18/002,494) entitled “Methods for achieving viral remission using long-acting antiretroviral agents”.","formattedTitle":"SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4650825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4650825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Studies in SIV-infected macaques have shown that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posited that optimized ART regimens designed to have robust penetration in tissue reservoirs and provide long-lasting antiviral activity may be advantageous for HIV or SIV remission. Macaques infected with RT-SHIV received oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir and rilpivirine without (n=4) or with (n=4) the immune activator vesatolimod after the initial onset of viremia. All animals were fully suppressed during treatment (4-12 months) and showed no virus rebound during a follow up period of 1.5-2 years despite CD8+ T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a new type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation.","manuscriptTitle":"SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-31 03:53:03","doi":"10.21203/rs.3.rs-4650825/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"53dadc17-73f3-4801-97bc-ccc50a1892ca","owner":[],"postedDate":"July 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":34756817,"name":"Health sciences/Diseases/Infectious diseases/HIV infections"},{"id":34756818,"name":"Biological sciences/Microbiology/Virology/Retrovirus"}],"tags":[],"updatedAt":"2024-11-21T19:40:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-31 03:53:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4650825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4650825","identity":"rs-4650825","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}