{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T14:01:57Z","timestamp":1700575317726},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,5,2]],"date-time":"2008-05-02T00:00:00Z","timestamp":1209686400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells\/mm<jats:sup>3<\/jats:sup> {Interquartile range (IQR) -17, -104} and +85,332 copies\/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2334-8-59","type":"journal-article","created":{"date-parts":[[2009,8,7]],"date-time":"2009-08-07T09:25:15Z","timestamp":1249637115000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption"],"prefix":"10.1186","volume":"8","author":[{"given":"Kenneth H","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona R","family":"Loutfy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos M","family":"Tsoukas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole F","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,5,2]]},"reference":[{"key":"650_CR1","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1056\/NEJM199803263381301","volume":"338","author":"FJ Palella Jr.","year":"1998","unstructured":"Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998, 338: 853-860. 10.1056\/NEJM199803263381301.","journal-title":"N Engl J Med"},{"key":"650_CR2","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1056\/NEJM200102153440702","volume":"344","author":"SG Deeks","year":"2001","unstructured":"Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM: Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001, 344: 472-480. 10.1056\/NEJM200102153440702.","journal-title":"N Engl J Med"},{"key":"650_CR3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1097\/00002030-200401230-00011","volume":"18","author":"C Katlama","year":"2004","unstructured":"Katlama C, Dominguez S, Gourlain K, Duvivier C, Delaugerre C, Legrand M, Tubiana R, Reynes J, Molina JM, Peytavin G, Calvez V, Costagliola D: Benefit of treatment interruption in HIV-infected patients with multiple therapeutic failures: a randomized controlled trial (ANRS 097). AIDS. 2004, 18: 217-226. 10.1097\/00002030-200401230-00011.","journal-title":"AIDS"},{"key":"650_CR4","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1056\/NEJMoa035103","volume":"349","author":"J Lawrence","year":"2003","unstructured":"Lawrence J, Mayers DL, Hullsiek KH, Collins G, Abrams DI, Reisler RB, Crane LR, Schmetter BS, Dionne TJ, Saldanha JM, Jones MC, Baxter JD: Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. N Engl J Med. 2003, 349: 837-846. 10.1056\/NEJMoa035103.","journal-title":"N Engl J Med"},{"key":"650_CR5","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1056\/NEJMoa062360","volume":"355","author":"WM El Sadr","year":"2006","unstructured":"El Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C: CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006, 355: 2283-2296. 10.1056\/NEJMoa062360.","journal-title":"N Engl J Med"},{"key":"650_CR6","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1440-1711.2004.01204.x","volume":"82","author":"J Gamberg","year":"2004","unstructured":"Gamberg J, Pardoe I, Bowmer MI, Howley C, Grant M: Lack of CD28 expression on HIV-specific cytotoxic T lymphocytes is associated with disease progression. Immunol Cell Biol. 2004, 82: 38-46. 10.1111\/j.1440-1711.2004.01204.x.","journal-title":"Immunol Cell Biol"},{"key":"650_CR7","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1084\/jem.20021288","volume":"198","author":"MS Topp","year":"2003","unstructured":"Topp MS, Riddell SR, Akatsuka Y, Jensen MC, Blattman JN, Greenberg PD: Restoration of CD28 expression in CD28-CD8+ memory effector T cells reconstitute antigen-induced IL-2 production. J Exp Med. 2003, 198: 947-955. 10.1084\/jem.20021288.","journal-title":"J Exp Med"},{"key":"650_CR8","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1182\/blood-2002-07-2103","volume":"101","author":"JM Brenchley","year":"2003","unstructured":"Brenchley JM, Karandikar NJ, Betts MR, Ambrozak DR, Hill BJ, Crotty LE, Casazza JP, Kuruppu J, Migueles SA, Connors M, Roederer M, Douek DC, Koup RA: Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood. 2003, 101: 2711-2720. 10.1182\/blood-2002-07-2103.","journal-title":"Blood"},{"key":"650_CR9","doi-asserted-by":"publisher","first-page":"8415","DOI":"10.4049\/jimmunol.175.12.8415","volume":"175","author":"BE Palmer","year":"2005","unstructured":"Palmer BE, Blyveis N, Fontenot AP, Wilson CC: Functional and phenotypic characterization of CD57+CD4+ T cells and their association with HIV-1-induced T cell dysfunction. J Immunol. 2005, 175: 8415-8423.","journal-title":"J Immunol"},{"key":"650_CR10","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/ni845","volume":"3","author":"SA Migueles","year":"2002","unstructured":"Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan CW, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, Connors M: HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol. 2002, 3: 1061-1068. 10.1038\/ni845.","journal-title":"Nat Immunol"},{"key":"650_CR11","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1084\/jem.20031598","volume":"198","author":"SA Younes","year":"2003","unstructured":"Younes SA, Yassine-Diab B, Dumont AR, Boulassel MR, Grossman Z, Routy JP, Sekaly RP: HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J Exp Med. 2003, 198: 1909-1922. 10.1084\/jem.20031598.","journal-title":"J Exp Med"},{"key":"650_CR12","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1172\/JCI118845","volume":"98","author":"RD Schrier","year":"1996","unstructured":"Schrier RD, Wiley CA, Spina C, McCutchan JA, Grant I: Pathogenic and protective correlates of T cell proliferation in AIDS. HNRC Group. HIV Neurobehavioral Research Center. J Clin Invest. 1996, 98: 731-740. 10.1172\/JCI118845.","journal-title":"J Clin Invest"},{"key":"650_CR13","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1097\/00002030-200209060-00008","volume":"16","author":"F Garcia","year":"2002","unstructured":"Garcia F, Plana M, Mestre G, Arnedo M, Gil C, Miro JM, Cruceta A, Pumarola T, Gallart T, Gatell JM: Immunological and virological factors at baseline may predict response to structured therapy interruption in early stage chronic HIV-1 infection. AIDS. 2002, 16: 1761-1765. 10.1097\/00002030-200209060-00008.","journal-title":"AIDS"},{"key":"650_CR14","first-page":"2381","volume":"18","author":"A Boschi","year":"2004","unstructured":"Boschi A, Tinelli C, Ortolani P, Moscatelli G, Morigi G, Arlotti M: CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy. AIDS. 2004, 18: 2381-2389.","journal-title":"AIDS"},{"key":"650_CR15","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/00002030-200501030-00006","volume":"19","author":"R Thiebaut","year":"2005","unstructured":"Thiebaut R, Pellegrin I, Chene G, Viallard JF, Fleury H, Moreau JF, Pellegrin JL, Blanco P: Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells\/l. AIDS. 2005, 19: 53-61.","journal-title":"AIDS"},{"key":"650_CR16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0140-6736(04)16589-6","volume":"364","author":"B Ledergerber","year":"2004","unstructured":"Ledergerber B, Lundgren JD, Walker AS, Sabin C, Justice A, Reiss P, Mussini C, Wit F, d'Arminio MA, Weber R, Fusco G, Staszewski S, Law M, Hogg R, Lampe F, Gill MJ, Castelli F, Phillips AN: Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet. 2004, 364: 51-62. 10.1016\/S0140-6736(04)16589-6.","journal-title":"Lancet"},{"key":"650_CR17","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.4049\/jimmunol.174.2.1037","volume":"174","author":"A Harari","year":"2005","unstructured":"Harari A, Vallelian F, Meylan PR, Pantaleo G: Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J Immunol. 2005, 174: 1037-1045.","journal-title":"J Immunol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-8-59.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2334-8-59\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-8-59","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2334-8-59.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T09:35:43Z","timestamp":1630488943000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/1471-2334-8-59"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,2]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["650"],"URL":"https:\/\/doi.org\/10.1186\/1471-2334-8-59","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,2]]},"assertion":[{"value":"1 May 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"59"}}