Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation

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new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="n5OnSYI4JoTvISUmAXFF0B6zb2KEiY7KrS9sbpLbaTI6ry1tKPVQ0cQ3Jq5MNoNc"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="n5OnSYI4JoTvISUmAXFF0B6zb2KEiY7KrS9sbpLbaTI6ry1tKPVQ0cQ3Jq5MNoNc"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="n5OnSYI4JoTvISUmAXFF0B6zb2KEiY7KrS9sbpLbaTI6ry1tKPVQ0cQ3Jq5MNoNc"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="n5OnSYI4JoTvISUmAXFF0B6zb2KEiY7KrS9sbpLbaTI6ry1tKPVQ0cQ3Jq5MNoNc"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="39352388"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" 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  <header class="heading" id="heading"> <div class="full-view" id="full-view-heading"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="The Journal of clinical investigation" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal The Journal of clinical investigation" data-pinger-ignore> J Clin Invest </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal The Journal of clinical investigation"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22J+Clin+Invest%22%5Bjour%5D&sort=date&sort_order=desc" 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class="citation-doi"> doi: 10.1172/JCI176358. </span> </div> <h1 class="heading-title"> Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Kincer+LP&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Laura P Kincer">Laura P Kincer</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Dravid+A&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ameet Dravid">Ameet Dravid</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Medicine, Poona Hospital and Research Center, Pune, India." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Ruby Hall Clinic, Pune, India." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Trunfio+M&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mattia Trunfio">Mattia Trunfio</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Calcagno+A&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Andrea Calcagno">Andrea Calcagno</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="ASL "CIttà di Torino," Torino, Italy." href="#full-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Zhou+S&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Shuntai Zhou">Shuntai Zhou</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Vercesi+R&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Riccardo Vercesi">Riccardo Vercesi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Spudich+S&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Serena Spudich">Serena Spudich</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, Yale University, New Haven, Connecticut, USA." href="#full-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gisslen+M&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Magnus Gisslen">Magnus Gisslen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden." href="#full-view-affiliation-8" ref="linksrc=author_aff"> 8 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden." href="#full-view-affiliation-9" ref="linksrc=author_aff"> 9 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Public Health Agency of Sweden, Solna, Sweden." href="#full-view-affiliation-10" ref="linksrc=author_aff"> 10 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Price+RW&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richard W Price">Richard W Price</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, University of California San Francisco, San Francisco, California, USA." href="#full-view-affiliation-11" ref="linksrc=author_aff"> 11 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Cinque+P&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paola Cinque">Paola Cinque</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy." href="#full-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Joseph+SB&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sarah B Joseph">Sarah B Joseph</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology and." href="#full-view-affiliation-12" ref="linksrc=author_aff"> 12 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#full-view-affiliation-13" ref="linksrc=author_aff"> 13 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/39352388/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> Department of Medicine, Poona Hospital and Research Center, Pune, India.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Ruby Hall Clinic, Pune, India.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy.</li> <li data-affiliation-id="full-view-affiliation-5" id="full-view-affiliation-5" ><sup class="key">5</sup> ASL "CIttà di Torino," Torino, Italy.</li> <li data-affiliation-id="full-view-affiliation-6" id="full-view-affiliation-6" ><sup class="key">6</sup> Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.</li> <li data-affiliation-id="full-view-affiliation-7" id="full-view-affiliation-7" ><sup class="key">7</sup> Department of Neurology, Yale University, New Haven, Connecticut, USA.</li> <li data-affiliation-id="full-view-affiliation-8" id="full-view-affiliation-8" ><sup class="key">8</sup> Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.</li> <li data-affiliation-id="full-view-affiliation-9" id="full-view-affiliation-9" ><sup class="key">9</sup> Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.</li> <li data-affiliation-id="full-view-affiliation-10" id="full-view-affiliation-10" ><sup class="key">10</sup> Public Health Agency of Sweden, Solna, Sweden.</li> <li data-affiliation-id="full-view-affiliation-11" id="full-view-affiliation-11" ><sup class="key">11</sup> Department of Neurology, University of California San Francisco, San Francisco, California, USA.</li> <li data-affiliation-id="full-view-affiliation-12" id="full-view-affiliation-12" ><sup class="key">12</sup> Department of Microbiology and Immunology and.</li> <li data-affiliation-id="full-view-affiliation-13" id="full-view-affiliation-13" ><sup class="key">13</sup> UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">39352388</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC11444166&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11444166/" data-ga-category="full_text" data-ga-action="PMCID" > PMC11444166 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1172/JCI176358&id_type=DOI" href="https://doi.org/10.1172/jci176358" data-ga-category="full_text" data-ga-action="DOI" > 10.1172/JCI176358 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Laura P Kincer</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> J Clin Invest<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2024">2024</time><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/39352388/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span 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Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Dravid+A&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ameet Dravid">Ameet Dravid</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Medicine, Poona Hospital and Research Center, Pune, India." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Ruby Hall Clinic, Pune, India." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Trunfio+M&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Mattia Trunfio">Mattia Trunfio</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Calcagno+A&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Andrea Calcagno">Andrea Calcagno</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="ASL "CIttà di Torino," Torino, Italy." href="#short-view-affiliation-5" ref="linksrc=author_aff"> 5 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Zhou+S&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Shuntai Zhou">Shuntai Zhou</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Vercesi+R&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Riccardo Vercesi">Riccardo Vercesi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Spudich+S&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Serena Spudich">Serena Spudich</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, Yale University, New Haven, Connecticut, USA." href="#short-view-affiliation-7" ref="linksrc=author_aff"> 7 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gisslen+M&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Magnus Gisslen">Magnus Gisslen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden." href="#short-view-affiliation-8" ref="linksrc=author_aff"> 8 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden." href="#short-view-affiliation-9" ref="linksrc=author_aff"> 9 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Public Health Agency of Sweden, Solna, Sweden." href="#short-view-affiliation-10" ref="linksrc=author_aff"> 10 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Price+RW&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richard W Price">Richard W Price</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, University of California San Francisco, San Francisco, California, USA." href="#short-view-affiliation-11" ref="linksrc=author_aff"> 11 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Cinque+P&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Paola Cinque">Paola Cinque</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy." href="#short-view-affiliation-6" ref="linksrc=author_aff"> 6 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Joseph+SB&cauthor_id=39352388" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sarah B Joseph">Sarah B Joseph</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Microbiology and Immunology and." href="#short-view-affiliation-12" ref="linksrc=author_aff"> 12 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA." href="#short-view-affiliation-13" ref="linksrc=author_aff"> 13 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Department of Medicine, Poona Hospital and Research Center, Pune, India.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Ruby Hall Clinic, Pune, India.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Unit of Infectious Diseases, Department of Medical Sciences, University of Turin at the "Amedeo di Savoia" Hospital, Torino, Italy.</li> <li data-affiliation-id="short-view-affiliation-5" id="short-view-affiliation-5" ><sup class="key">5</sup> ASL "CIttà di Torino," Torino, Italy.</li> <li data-affiliation-id="short-view-affiliation-6" id="short-view-affiliation-6" ><sup class="key">6</sup> Unit of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.</li> <li data-affiliation-id="short-view-affiliation-7" id="short-view-affiliation-7" ><sup class="key">7</sup> Department of Neurology, Yale University, New Haven, Connecticut, USA.</li> <li data-affiliation-id="short-view-affiliation-8" id="short-view-affiliation-8" ><sup class="key">8</sup> Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.</li> <li data-affiliation-id="short-view-affiliation-9" id="short-view-affiliation-9" ><sup class="key">9</sup> Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.</li> <li data-affiliation-id="short-view-affiliation-10" id="short-view-affiliation-10" ><sup class="key">10</sup> Public Health Agency of Sweden, Solna, Sweden.</li> <li data-affiliation-id="short-view-affiliation-11" id="short-view-affiliation-11" ><sup class="key">11</sup> Department of Neurology, University of California San Francisco, San Francisco, California, USA.</li> <li data-affiliation-id="short-view-affiliation-12" id="short-view-affiliation-12" ><sup class="key">12</sup> Department of Microbiology and Immunology and.</li> <li data-affiliation-id="short-view-affiliation-13" id="short-view-affiliation-13" ><sup class="key">13</sup> UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">39352388</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC11444166&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11444166/" data-ga-category="full_text" data-ga-action="PMCID" > PMC11444166 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1172/JCI176358&id_type=DOI" href="https://doi.org/10.1172/jci176358" data-ga-category="full_text" data-ga-action="DOI" > 10.1172/JCI176358 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation 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id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> During antiretroviral therapy (ART), most people living with HIV-1 have undetectable HIV-1 RNA in their plasma. However, they occasionally present with new or progressive neurologic deficits and detectable HIV-1 RNA in the cerebrospinal fluid (CSF), a condition defined as neurosymptomatic HIV-1 CSF escape (NSE). We explored the source of neuropathogenesis and HIV-1 RNA in the CSF during NSE by characterizing HIV-1 populations and inflammatory biomarkers in CSF from 25 individuals with NSE. HIV-1 populations in the CSF were uniformly drug resistant and adapted to replication in CD4+ T cells, but differed greatly in genetic diversity, with some having low levels of diversity similar to those observed during untreated primary infection and others having high levels like those during untreated chronic infection. Higher diversity in the CSF during NSE was associated with greater CNS inflammation. Finally, optimization of ART regimen was associated with viral suppression and improvement of neurologic symptoms. These results are consistent with CNS inflammation and neurologic injury during NSE being driven by replication of partially drug-resistant virus in CNS CD4+ T cells. This is unlike nonsuppressible viremia in the plasma during ART, which typically lacks clinical consequences and is generated by virus expression without replication. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> AIDS/HIV; Neurological disorders; T cells. </p> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" data-ga-category="literature_resources" data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/2743546330c8/jci-134-176358-g085.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="735" data-image-height="856" data-image-alt="Figure 1" data-pmc-id="PMC11444166" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/f943b21b6039/jci-134-176358-g085.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="735"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="856"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1. HIV-1 NSE populations can be… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1. HIV-1 NSE populations can be very genetically diverse. </p> </strong> <div class="figure-caption-contents"><p> ( <b> A </b> ) To facilitate… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1. HIV-1 NSE populations can be very genetically diverse. </strong> <div class="figure-caption-contents">(<b>A</b>) To facilitate plotting on a log scale, a constant (0.005) was added to all PWD values and then log transformed. PWD was calculated across all lineages in the CSF of NSE participants (blue) and untreated controls (gray). When multiple major lineages were present in a CSF NSE population, PWD was also calculated within each major lineage, thus avoiding between-lineage comparisons (orange). Means are marked with a vertical line in orange or blue. For individuals with both types of PWD calculations (shown in blue and orange), the mean value of the within-lineage comparison (orange) was used for downstream analyses. A PWD value of 0.004 roughly separated the diversity observed during primary infection from levels observed during chronic infection. The value corresponding to this cutoff is marked with a vertical gray line. Participants with mean PWD above 0.004 are marked with an asterisk. (<b>B</b>) Mean PWD was calculated for the CSF of 2 participants with ASE (PWD less than 0.004, purple closed diamond; PWD above 0.004, purple open diamond; ref. 18) and 25 participants with NSE (PWD below 0.004, gray closed diamonds; PWD above 0.004, black open diamonds). Median is shown with the horizontal bar. (<b>C</b>) Mean PWDs of lower (<i>n</i> = 14) and higher (<i>n</i> = 11) diversity NSE populations were compared with blood- (closed red triangles, <i>n</i> = 7) and CSF-derived (closed blue circles, <i>n</i> = 7) virus from untreated primary infection and blood- (open red triangles, <i>n</i> = 7) and CSF-derived (open blue circles, <i>n</i> = 7) virus from untreated chronic infection. **<i>P</i> < 0.001; ***<i>P</i> < 0.0001; ****<i>P</i> < 0.0001, Mann-Whitney <i>U</i> test. Median value of the mean PWDs is shown with the horizontal bar.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/cc7ea509a24a/jci-134-176358-g086.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="750" data-image-height="658" data-image-alt="Figure 2" data-pmc-id="PMC11444166" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/244703a0dc2e/jci-134-176358-g086.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="750"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="658"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2. Phylogenetic trees of HIV-1 NSE… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2. Phylogenetic trees of HIV-1 NSE populations. </p> </strong> <div class="figure-caption-contents"><p> Genetic diversity during HIV-1 NSE was assessed… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2. Phylogenetic trees of HIV-1 NSE populations. </strong> <div class="figure-caption-contents">Genetic diversity during HIV-1 NSE was assessed using SGA and/or Illumina MiSeq Deep Sequencing with Primer ID. CSF-derived (in blue) partial <i>env</i> neighbor-joining phylogenetic trees of participants with NSE. Trees are ordered (in rows) from lowest to highest mean PWD. Asterisks designate the “higher diversity” participants with mean PWD above 0.004.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/689fcdd12de3/jci-134-176358-g087.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="767" data-image-height="866" data-image-alt="Figure 3" data-pmc-id="PMC11444166" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/93a4bfb5da4b/jci-134-176358-g087.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="767"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="866"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3. Mean PWD is correlated with… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3. Mean PWD is correlated with CSF HIV-1 RNA. </p> </strong> <div class="figure-caption-contents"><p> Linear regressions were performed to… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3. Mean PWD is correlated with CSF HIV-1 RNA. </strong> <div class="figure-caption-contents">Linear regressions were performed to look for relationships between mean PWD and plasma HIV-1 RNA (<b>A</b>), CSF HIV-1 RNA (<b>B</b>), CSF: plasma HIV-1 RNA log<sub>10</sub> Δ (<b>C</b>), blood CD4<sup>+</sup> T cell count (<b>D</b>), nadir blood CD4<sup>+</sup> T cell count (<b>E</b>), and CSF WBC count (<b>F</b>). The relationship between mean PWD and CSF HIV-1 RNA (<b>B</b>, <i>R<sup>2</sup></i> = 0.3536, <i>P</i> = 0.0089) was the only statistically significant comparison. All <i>P</i> values were adjusted for multiple comparisons.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/8dee87b6677b/jci-134-176358-g088.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="766" data-image-height="751" data-image-alt="Figure 4" data-pmc-id="PMC11444166" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/7d5e38dc978e/jci-134-176358-g088.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="766"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="751"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4. NSE virus is adapted to… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4. NSE virus is adapted to replicating in CD4 <sup> + </sup> T cells. </p> </strong> <div class="figure-caption-contents"><p> ( <b> A </b> )… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4. NSE virus is adapted to replicating in CD4<sup>+</sup> T cells. </strong> <div class="figure-caption-contents">(<b>A</b>) Full-length CSF-derived HIV <i>envs</i> generated by SGA were cloned and used to produce pseudoviruses that were then tested in our Affinofile assay for their ability to facilitate entry into cells with low levels of CD4. None of the NSE <i>envs</i> tested were able to efficiently enter cells with low levels of CD4, but rather required high surface density of CD4 for efficient entry, indicating that the virus was adapted to replicating in T cells. Median relative infectivity values for 2 to 4 biological replicates are plotted with bars, and each individual point is shown with a circle. Representative CSF <i>envs</i> from both the lower diversity group (<i>n</i> = 8) and the higher diversity group (<i>n</i> = 9) were tested (blue bars and circles) as well as macrophage-tropic and T cell–tropic controls (black bars and circles). (<b>B</b>) CSF WBC counts in the NSE cohort and each comparator cohort. Mann-Whitney <i>U</i> tests were performed and found the ART-suppressed cohort (<i>n</i> = 49) had significantly lower CSF WBC counts than participants with NSE (<i>n</i> = 25), untreated primary infection (<i>n</i> = 7), and untreated chronic infection (<i>n</i> = 7): ****<i>P</i> = 0.0002; ****<i>P</i> = 0.0002; **<i>P</i> = 0.0044, respectively. All <i>P</i> values were corrected for multiple comparisons. Median values are shown with horizontal bars.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/23b47c2b5c23/jci-134-176358-g089.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="735" data-image-height="916" data-image-alt="Figure 5" data-pmc-id="PMC11444166" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/92c770821579/jci-134-176358-g089.gif" alt="Figure 5" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="735"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="916"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5. Inflammatory biomarkers in the CSF… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5. Inflammatory biomarkers in the CSF are elevated in participants with NSE compared with… </p> </strong> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5. Inflammatory biomarkers in the CSF are elevated in participants with NSE compared with ART-suppressed controls and trend higher in NSE participants with high-diversity viral populations compared with NSE participants with low-diversity viral populations. </strong> <div class="figure-caption-contents">We measured 1,472 protein biomarkers (Olink platform) in CSF of 18 NSE participants and 49 ART-suppressed controls. (<b>A</b>) Volcano plot comparing CSF biomarker levels during NSE to levels in suppressed controls. Levels of 678 biomarkers were significantly different after correction for multiple comparisons (red circles, most higher in NSE). The 10 biomarkers with the lowest adjusted <i>P</i> values are labeled. (<b>B</b>) Distributions (quartiles) of these 10 biomarkers are shown. (<b>C</b>) Venn diagram of the 705 CSF biomarkers that are significantly different between NSE participants and suppressed controls. (<b>D</b>) Volcano plot comparing CSF biomarkers in participants with lower versus higher diversity NSE populations. No markers were significantly different, but there was a trend for the CSF biomarkers to be higher in participants with higher diversity NSE (majority of circles to the right of 0 on the <i>x</i> axis). (<b>E</b>) Overrepresentation analysis of gene ontogeny biological processes. The 14 most overrepresented pathways in the CSF of NSE participants compared with ART-suppressed controls are shown. The color of each circle indicates the adjusted <i>P</i> value, and the size of the circle represents count. We found that 40% of the genes that were overrepresented in the CSF of NSE participants compared with ART-suppressed controls were involved in the immune response (top row).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="5" data-label-slug="figure-6"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/d6499309e2e5/jci-134-176358-g090.jpg" itemprop="contentUrl" aria-describedby="figure-caption-5" role="button" data-image-width="747" data-image-height="395" data-image-alt="Figure 6" data-pmc-id="PMC11444166" data-figure-id="F6"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-5" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8433/11444166/063331d522b6/jci-134-176358-g090.gif" alt="Figure 6" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="747"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="395"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 6. Model of the emergence of… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 6. Model of the emergence of NSE during treatment with an ART regimen representative… </p> </strong> </div> <figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 6. Model of the emergence of NSE during treatment with an ART regimen representative of those used in this cohort. </strong> <div class="figure-caption-contents">(i) Most drugs are at lower concentrations in the CSF (86). Despite the overall low levels of protein in the CSF, most ATV in the CSF is protein bound (54), thus reducing the amount of available ATV (54) to noninhibitory levels (86). In contrast, TDF and 3TC are primarily unbound in the CSF. In this drug regimen (TDF/3TC/ATV/r, the most common regimen in our cohort), 3TC is likely the only drug at inhibitory levels in CSF. During a period of poor adherence, the concentration of drug falls and the CSF HIV-1 RNA rises. Upon returning to adherence, drug levels rise and HIV-1 RNA decreases. Return to adherence will select for the M184V mutation (conveying resistance to 3TC). (ii) Resistant virus can reach the CNS as a migrating CD4<sup>+</sup> T cell carrying a provirus with the M184V mutation or (iii) evolve in the CNS during replication when all 3 drugs are at noninhibitory levels. (iv) HIV-1 RNA in the CSF remains detectable and may increase as the drug-resistant virus replicates. (v and vi) Replication increases genetic diversity, CSF HIV-1 RNA, and inflammatory biomarkers. Both v and vi are associated with the spread of drug resistant virus and an elevation in CSF WBC. (vii) Optimization of ART to a regimen with good CNS penetration and to which the NSE virus is sensitive will (viii) stop replication and improve symptoms. 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href="/?term=%22HIV+Infections%2Fblood%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV+Infections%2Fblood%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV Infections/blood"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV Infections* / blood"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV Infections* / blood"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV Infections/blood"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV Infections/blood"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword HIV Infections* / cerebrospinal fluid" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-6" aria-expanded="false" data-pinger-ignore> HIV Infections* / cerebrospinal fluid </button><div id="keyword-actions-mesh-terms-major-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword HIV Infections* / cerebrospinal fluid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22HIV+Infections%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV+Infections%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV Infections/cerebrospinal fluid"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV Infections* / cerebrospinal fluid"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV Infections* / cerebrospinal fluid"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV Infections/cerebrospinal fluid"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV Infections/cerebrospinal fluid"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword HIV Infections* / drug therapy" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-7" aria-expanded="false" data-pinger-ignore> HIV Infections* / drug therapy </button><div id="keyword-actions-mesh-terms-major-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword HIV Infections* / drug therapy"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22HIV+Infections%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV+Infections%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV Infections/drug therapy"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV Infections* / drug therapy"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV Infections* / drug therapy"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV Infections/drug therapy"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV Infections/drug therapy"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword HIV Infections* / immunology" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-8" aria-expanded="false" data-pinger-ignore> HIV Infections* / immunology </button><div id="keyword-actions-mesh-terms-major-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword HIV Infections* / immunology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22HIV+Infections%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV+Infections%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV Infections/immunology"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV Infections* / immunology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV Infections* / immunology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV Infections/immunology"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV Infections/immunology"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword HIV Infections* / virology" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-9" aria-expanded="false" data-pinger-ignore> HIV Infections* / virology </button><div id="keyword-actions-mesh-terms-major-9" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword HIV Infections* / virology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22HIV+Infections%2Fvirology%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV+Infections%2Fvirology%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV Infections/virology"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV Infections* / virology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV Infections* / virology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV Infections/virology"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV Infections/virology"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword HIV-1* / immunology" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-10" aria-expanded="false" data-pinger-ignore> HIV-1* / immunology </button><div id="keyword-actions-mesh-terms-major-10" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword HIV-1* / immunology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22HIV-1%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22HIV-1%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="HIV-1/immunology"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="HIV-1* / immunology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=HIV-1" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="HIV-1* / immunology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""HIV-1/immunology"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""HIV-1/immunology"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Humans" tabindex="0" aria-controls="keyword-actions-mesh-terms-11" aria-expanded="false" data-pinger-ignore> Humans </button><div id="keyword-actions-mesh-terms-11" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Humans"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Humans"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Humans" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Humans"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Humans"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Humans"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Inflammation / cerebrospinal fluid" tabindex="0" aria-controls="keyword-actions-mesh-terms-12" aria-expanded="false" data-pinger-ignore> Inflammation / cerebrospinal fluid </button><div id="keyword-actions-mesh-terms-12" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Inflammation / cerebrospinal fluid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Inflammation%2Fcerebrospinal+fluid%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Inflammation%2Fcerebrospinal+fluid%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Inflammation/cerebrospinal fluid"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Inflammation / cerebrospinal fluid"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Inflammation" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Inflammation / cerebrospinal fluid"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Inflammation/cerebrospinal fluid"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Inflammation/cerebrospinal fluid"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Inflammation / immunology" tabindex="0" aria-controls="keyword-actions-mesh-terms-13" aria-expanded="false" data-pinger-ignore> Inflammation / immunology </button><div id="keyword-actions-mesh-terms-13" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Inflammation / immunology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Inflammation%2Fimmunology%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Inflammation%2Fimmunology%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Inflammation/immunology"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Inflammation / immunology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Inflammation" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Inflammation / immunology"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Inflammation/immunology"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Inflammation/immunology"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Male" tabindex="0" aria-controls="keyword-actions-mesh-terms-14" aria-expanded="false" data-pinger-ignore> Male </button><div id="keyword-actions-mesh-terms-14" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Male"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Male"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Male"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Male" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Male"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Male"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Male"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Middle Aged" tabindex="0" aria-controls="keyword-actions-mesh-terms-15" aria-expanded="false" data-pinger-ignore> Middle Aged </button><div id="keyword-actions-mesh-terms-15" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Middle Aged"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Middle Aged"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Middle Aged"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Middle+Aged" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Middle Aged"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Middle Aged"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Middle Aged"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword RNA, Viral* / blood" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-16" aria-expanded="false" data-pinger-ignore> RNA, Viral* / blood </button><div id="keyword-actions-mesh-terms-major-16" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Viral* / blood"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Viral%2Fblood%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Viral%2Fblood%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Viral/blood"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA, Viral* / blood"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA%2C+Viral" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA, Viral* / blood"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Viral/blood"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Viral/blood"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword RNA, Viral* / cerebrospinal fluid" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-17" aria-expanded="false" data-pinger-ignore> RNA, Viral* / cerebrospinal fluid </button><div id="keyword-actions-mesh-terms-major-17" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Viral* / cerebrospinal fluid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Viral%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Viral%2Fcerebrospinal+fluid%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Viral/cerebrospinal fluid"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA, Viral* / cerebrospinal fluid"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA%2C+Viral" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA, Viral* / cerebrospinal fluid"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Viral/cerebrospinal fluid"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Viral/cerebrospinal fluid"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Virus Replication*" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-18" aria-expanded="false" data-pinger-ignore> Virus Replication* </button><div id="keyword-actions-mesh-terms-major-18" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Virus Replication*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Virus+Replication%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Virus+Replication%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Virus Replication"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Virus Replication*"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Virus+Replication" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Virus Replication*"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Virus Replication"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Virus Replication"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA, Viral" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> RNA, Viral </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Viral"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Viral%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Viral%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RNA, Viral"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RNA, Viral"> Search in PubMed </a></li><li><a class="search-in-mesh-link 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Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation - PubMed