{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T19:50:46Z","timestamp":1774122646362,"version":"3.50.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,9,25]],"date-time":"2005-09-25T00:00:00Z","timestamp":1127606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,9,25]],"date-time":"2005-09-25T00:00:00Z","timestamp":1127606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Immune Based Ther Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1<jats:sup>+<\/jats:sup> individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for na\u00efve and activation markers, and <jats:italic>in vitro<\/jats:italic> proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Median CD4 T-cell counts in IRIS patients rose from 22 cells\/\u03bcl before initiation of ART, to 70 cells\/\u03bcl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of na\u00efve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells\/\u03bcl at baseline, which rose to 249 cells\/\u03bcl 6 months post ART, when strong T-cell responses were seen in &gt; 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS &gt; CP &gt; UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct\/augment T-cell immunity in such setting resulting in clinical benefit.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1476-8518-3-7","type":"journal-article","created":{"date-parts":[[2005,9,27]],"date-time":"2005-09-27T06:14:11Z","timestamp":1127801651000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: Beneficial effect of IL-2 and GM-CSF immunotherapy"],"prefix":"10.1186","volume":"3","author":[{"given":"A","family":"Pires","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AL","family":"Pozniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Gazzard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Gotch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Imami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,9,25]]},"reference":[{"key":"21_CR1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1089\/08892220252779638","volume":"18","author":"AL Landay","year":"2002","unstructured":"Landay AL, Bettendorf D, Chan E, Spritzler J, Schmitz JL, Bucy RP, Gonzalez CJ, Schnizlein-Bick CT, Evans T, Squires KE, et al: Evidence of immune reconstitution in antiretroviral drug-experienced patients with advanced HIV disease. 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