{"id":446415,"date":"2017-12-04T15:43:45","date_gmt":"2017-12-04T23:43:45","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/?post_type=msr-research-item&#038;p=446415"},"modified":"2018-10-16T20:06:56","modified_gmt":"2018-10-17T03:06:56","slug":"lower-viral-loads-slower-cd4-t-cell-count-decline-mrkad5-hiv-1-vaccinees-expressing-disease-susceptible-hla-b5802","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/lower-viral-loads-slower-cd4-t-cell-count-decline-mrkad5-hiv-1-vaccinees-expressing-disease-susceptible-hla-b5802\/","title":{"rendered":"Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02"},"content":{"rendered":"<p><strong><em>Background.<\/em><\/strong>\u2003HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8<sup>+<\/sup>\u00a0T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag\/Pol\/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent.<\/p>\n<p><strong><em>Methods.<\/em><\/strong>\u2003Viral loads, CD4<sup>+<\/sup>\u00a0T-cell counts, and enzyme-linked immunospot assay\u2013determined anti-HIV-1 CD8<sup>+<\/sup>\u00a0T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed.<\/p>\n<p><strong><em>Results.<\/em><\/strong>\u2003Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies\/mL;\u00a0<em>P<\/em>\u00a0= .01), a 0.76 log<sub>10<\/sub>\u00a0lower longitudinal viremia level (<em>P<\/em>\u00a0= .01), and slower progression to a CD4<sup>+<\/sup>\u00a0T-cell count of <350 cells\/mm<sup>3<\/sup>\u00a0(<em>P<\/em>\u00a0= .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses;\u00a0<em>P<\/em>\u00a0= .04) and magnitude (2300 vs 70 spot-forming cells\/10<sup>6<\/sup>peripheral blood mononuclear cells;\u00a0<em>P<\/em>\u00a0= .06) in vaccinees versus placebo recipients.<\/p>\n<p><strong><em>Conclusions.<\/em><\/strong>\u2003In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4<sup>+<\/sup>\u00a0T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition.<\/p>\n<p><strong>Clinical Trials Registration.<\/strong>\u2003NCT00413725, DOH-27-0207-1539.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Background.\u2003HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8+\u00a0T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag\/Pol\/Nef vaccine in a subset of the infected Phambili cohort [&hellip;]<\/p>\n","protected":false},"featured_media":230089,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"Oxford University Press","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"3","msr_edition":"","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"The Journal of infectious diseases","msr_number":"","msr_organization":"","msr_pages_string":"379-389","msr_page_range_start":"379","msr_page_range_end":"389","msr_series":"","msr_volume":"214","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1093\/infdis\/jiw093","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"","msr_other_contributors":"","msr_speaker":"","msr_award":"","msr_affiliation":"","msr_institution":"","msr_host":"","msr_version":"","msr_duration":"","msr_original_fields_of_study":"","msr_release_tracker_id":"","msr_s2_match_type":"","msr_citation_count_updated":"","msr_published_date":"2016-03-06","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"https:\/\/academic.oup.com\/jid\/article\/214\/3\/379\/2577316","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_s2_pdf_url":"","msr_year":0,"msr_citation_count":0,"msr_influential_citations":0,"msr_reference_count":0,"msr_s2_match_confidence":0,"msr_microsoftintellectualproperty":true,"msr_s2_open_access":false,"msr_s2_author_ids":[],"msr_pub_ids":[],"msr_hide_image_in_river":0,"footnotes":""},"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-publisher":[],"msr-focus-area":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[],"msr-conference":[],"msr-journal":[],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-446415","msr-research-item","type-msr-research-item","status-publish","has-post-thumbnail","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"Oxford University Press","msr_edition":"","msr_affiliation":"","msr_published_date":"2016-03-06","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"379-389","msr_chapter":"3","msr_isbn":"","msr_journal":"The Journal of infectious diseases","msr_volume":"214","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":1,"msr_main_download":"446418","msr_publicationurl":"https:\/\/academic.oup.com\/jid\/article\/214\/3\/379\/2577316","msr_doi":"10.1093\/infdis\/jiw093","msr_publication_uploader":[{"type":"file","title":"Leitman et al. &#8211; 2017 &#8211; Lower Viral Loads and Slower CD4 T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease- Susceptible","viewUrl":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2017\/12\/Leitman-et-al.-2017-Lower-Viral-Loads-and-Slower-CD4-T-Cell-Count-Decline-in-MRKAd5-HIV-1-Vaccinees-Expressing-Disease-Susceptible.pdf","id":446418,"label_id":0},{"type":"url","title":"https:\/\/academic.oup.com\/jid\/article\/214\/3\/379\/2577316","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1093\/infdis\/jiw093","viewUrl":false,"id":false,"label_id":0}],"msr_related_uploader":"","msr_citation_count":0,"msr_citation_count_updated":"","msr_s2_paper_id":"","msr_influential_citations":0,"msr_reference_count":0,"msr_arxiv_id":"","msr_s2_author_ids":[],"msr_s2_open_access":false,"msr_s2_pdf_url":null,"msr_attachments":[{"id":0,"url":"https:\/\/academic.oup.com\/jid\/article\/214\/3\/379\/2577316"}],"msr-author-ordering":[{"type":"text","value":"Ellen M. 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