Blood biomarkers of expressed and inducible HIV-1

Blood biomarkers of expressed and inducible HIV-1

OBJECTIVE:To define the relationships between molecular measures of viral persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and expressed or inducible virus from resting CD4 T cells of individuals on suppressive antiretroviral therapy. DESIGN:We compared molecular measurement...

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Veröffentlicht in:AIDS (London) 2018-03, Vol.32 (6), p.699-708
Hauptverfasser: Cillo, Anthony R, Hong, Francis, Tsai, Angela, Irrinki, Alivelu, Kaur, Jasmine, Sloan, Derek D, Follen, Mattie, Geleziunas, Romas, Cihlar, Tomas, Win, Sandra S, Murry, Jeffrey P, Mellors, John W
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container_end_page 708
container_issue 6
container_start_page 699
container_title AIDS (London)
container_volume 32
creator Cillo, Anthony R
Hong, Francis
Tsai, Angela
Irrinki, Alivelu
Kaur, Jasmine
Sloan, Derek D
Follen, Mattie
Geleziunas, Romas
Cihlar, Tomas
Win, Sandra S
Murry, Jeffrey P
Mellors, John W
description OBJECTIVE:To define the relationships between molecular measures of viral persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and expressed or inducible virus from resting CD4 T cells of individuals on suppressive antiretroviral therapy. DESIGN:We compared molecular measurements of HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to the levels of virions produced by either unstimulated or phorbol myristate acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21 donors on suppressive antiretroviral therapy. RESULTS:We found that unstimulated virion release from cultured resting CD4 T cells was positively correlated with the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million uncultured PBMC were positively correlated with the levels of inducible virion release from both PMA/iono-stimulated PBMC (total HIV-1 DNArho = 0.64, P = 0.0017; unspliced HIV-1 RNArho = 0.77, P 
doi_str_mv 10.1097/QAD.0000000000001748
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DESIGN:We compared molecular measurements of HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to the levels of virions produced by either unstimulated or phorbol myristate acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21 donors on suppressive antiretroviral therapy. RESULTS:We found that unstimulated virion release from cultured resting CD4 T cells was positively correlated with the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million uncultured PBMC were positively correlated with the levels of inducible virion release from both PMA/iono-stimulated PBMC (total HIV-1 DNArho = 0.64, P = 0.0017; unspliced HIV-1 RNArho = 0.77, P &lt; 0.001) and PMA/iono-stimulated resting CD4 T cells (total HIV-1 DNArho = 0.75, P &lt; 0.001; unspliced HIV-1 RNArho = 0.75, P &lt; 0.001). CONCLUSION:These results show for the first time that there are strong associations between in-vivo measures of HIV-1 persistence and ex-vivo measures of spontaneous and inducible virus production from cultured PBMC and resting CD4 T cells. Findings from this study provide insight into the biology of HIV-1 persistence and suggest methods to guide the evaluation of clinical strategies to reduce the size of the viral reservoir.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0000000000001748</identifier><identifier>PMID: 29334544</identifier><language>eng</language><publisher>England: Copyright Wolters Kluwer Health, Inc</publisher><ispartof>AIDS (London), 2018-03, Vol.32 (6), p.699-708</ispartof><rights>Copyright © 2018 Wolters Kluwer Health, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5088-5ef2e0d093395eb986a254ffe39123f1ba31158243cff0bee34e4565574d099f3</citedby><cites>FETCH-LOGICAL-c5088-5ef2e0d093395eb986a254ffe39123f1ba31158243cff0bee34e4565574d099f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29334544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cillo, Anthony R</creatorcontrib><creatorcontrib>Hong, Francis</creatorcontrib><creatorcontrib>Tsai, Angela</creatorcontrib><creatorcontrib>Irrinki, Alivelu</creatorcontrib><creatorcontrib>Kaur, Jasmine</creatorcontrib><creatorcontrib>Sloan, Derek D</creatorcontrib><creatorcontrib>Follen, Mattie</creatorcontrib><creatorcontrib>Geleziunas, Romas</creatorcontrib><creatorcontrib>Cihlar, Tomas</creatorcontrib><creatorcontrib>Win, Sandra S</creatorcontrib><creatorcontrib>Murry, Jeffrey P</creatorcontrib><creatorcontrib>Mellors, John W</creatorcontrib><title>Blood biomarkers of expressed and inducible HIV-1</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>OBJECTIVE:To define the relationships between molecular measures of viral persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and expressed or inducible virus from resting CD4 T cells of individuals on suppressive antiretroviral therapy. DESIGN:We compared molecular measurements of HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to the levels of virions produced by either unstimulated or phorbol myristate acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21 donors on suppressive antiretroviral therapy. RESULTS:We found that unstimulated virion release from cultured resting CD4 T cells was positively correlated with the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million uncultured PBMC were positively correlated with the levels of inducible virion release from both PMA/iono-stimulated PBMC (total HIV-1 DNArho = 0.64, P = 0.0017; unspliced HIV-1 RNArho = 0.77, P &lt; 0.001) and PMA/iono-stimulated resting CD4 T cells (total HIV-1 DNArho = 0.75, P &lt; 0.001; unspliced HIV-1 RNArho = 0.75, P &lt; 0.001). CONCLUSION:These results show for the first time that there are strong associations between in-vivo measures of HIV-1 persistence and ex-vivo measures of spontaneous and inducible virus production from cultured PBMC and resting CD4 T cells. 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DESIGN:We compared molecular measurements of HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to the levels of virions produced by either unstimulated or phorbol myristate acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21 donors on suppressive antiretroviral therapy. RESULTS:We found that unstimulated virion release from cultured resting CD4 T cells was positively correlated with the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million uncultured PBMC were positively correlated with the levels of inducible virion release from both PMA/iono-stimulated PBMC (total HIV-1 DNArho = 0.64, P = 0.0017; unspliced HIV-1 RNArho = 0.77, P &lt; 0.001) and PMA/iono-stimulated resting CD4 T cells (total HIV-1 DNArho = 0.75, P &lt; 0.001; unspliced HIV-1 RNArho = 0.75, P &lt; 0.001). CONCLUSION:These results show for the first time that there are strong associations between in-vivo measures of HIV-1 persistence and ex-vivo measures of spontaneous and inducible virus production from cultured PBMC and resting CD4 T cells. Findings from this study provide insight into the biology of HIV-1 persistence and suggest methods to guide the evaluation of clinical strategies to reduce the size of the viral reservoir.</abstract><cop>England</cop><pub>Copyright Wolters Kluwer Health, Inc</pub><pmid>29334544</pmid><doi>10.1097/QAD.0000000000001748</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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title Blood biomarkers of expressed and inducible HIV-1
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