TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB. (28th January 2015)

• Record Type: Journal Article
• Authors: Haridas, Viraga; Pean, Polidy; Jasenosky, Luke D.; Madec, Yoann; Laureillard, Didier; Sok, Thim; Sath, Sun; Borand, Laurence; Marcy, Olivier; Chan, Sarin; Tsitsikov, Erdyni; Delfraissy, Jean-François; Blanc, François-Xavier; Goldfeld, Anne E.
• Is Part Of: AIDS. Volume 29:Number 3(2015)
• Publication Date: 2015-01-28
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000546
• Languages: English
• ISSNs: 0269-9370

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>To investigate the impact of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) upon immunological recovery and the T-cell compartment after initiation of TB and antiretroviral therapy (ART).</p> </sec> <sec> <title>Design and methods:</title> <p>We prospectively evaluated T-cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (<italic>n</italic> = 154) of highly immunosuppressed HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretrovirals randomized clinical trial. We compared findings from patients who developed TB-IRIS with findings from patients who did not develop TB-IRIS. Data were evaluated with mixed-effect linear regression, Kaplan–Meier estimates, and Wilcoxon rank-sum tests, and q-values were calculated to control for multiple comparisons.</p> </sec> <sec> <title>Results:</title> <p>Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR<sup>+</sup>CD45RO<sup>+</sup>CD4<sup>+</sup>, CCR5<sup>+</sup>CD4<sup>+</sup>, OX40<sup>+</sup>CD4<sup>+</sup>, and Fas<sup>+</sup> effector memory CD8<sup>+</sup> T cells, and significantly elevated levels of plasma interleukin (IL)-6, IL-1β, IL-8, and IL-10, and viral load. Post-ART initiation, effector memory CD4<sup>+</sup> and Fas<sup>+</sup> effector memory CD4<sup>+</sup> T-cell frequencies significantly expanded, and central memory CD4<sup>+</sup> T-cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, effector memory/central memory CD4<sup>+</sup> T-cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients.</p> </sec> <sec> <title>Conclusions:</title> <p>A distinct pattern of pre-ART T-cell and cytokine markers appear to poise the immune response of certain patients to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4<sup>+</sup> T-cell memory compartment towards an effector memory-dominated phenotype. We speculate that these pre and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome.</p> </sec> </abstract>