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 immunotherapyReport as inadecuate




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 - Download this document for free, or read online. Document in PDF available to download.

Journal of Immune Based Therapies and Vaccines

, 3:7

First Online: 25 September 2005Received: 06 April 2004Accepted: 25 September 2005

Abstract

BackgroundWith 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 individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy.

MethodsWe assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro 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.

ResultsMedian CD4 T-cell counts in IRIS patients rose from 22 cells-μl before initiation of ART, to 70 cells-μl after 8 months of therapy median 6.5 fold increase. This coincided with IRIS diagnosis, lower levels of naïve 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-μl at baseline, which rose to 249 cells-μl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC IRIS > CP > UC. Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery.

ConclusionThese 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.

KeywordsImmune reconstitution T cells HIV-1 Mycobacterial infection MAC Electronic supplementary materialThe online version of this article doi:10.1186-1476-8518-3-7 contains supplementary material, which is available to authorized users.

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Author: A Pires - M Nelson - AL Pozniak - M Fisher - B Gazzard - F Gotch - N Imami

Source: https://link.springer.com/







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