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Home >> Publications >> TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB.

Publication

Author(s):

Haridas V, Pean P, Jasenosky LD, Madec Y, Laureillard D, Sok T, Sath S, Borand L, Marcy O, Chan S, Tsitsikov E, Delfraissy JF, Blanc FX, Goldfeld AE; CAPRI-T (ANRS 12164) Study Team.

Pub Title:

TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB.

Pub Date:

Jan 28 2015

Pub Region(s):

Asia-Pacific

Journal:

Title: 
AIDS
Link: 
http://ovidsp.tx.ovid.com/sp-3.15.1b/ovidweb.cgi?QS2=434f4e1a73d37e8cd0a0337826dace8325ac91717eac72a50038109a2409b01e5c2b797bac9414cd2385d95128329b9c45a2fdc5d93c5c3206b60beb9bcf9c3723c78f0afc590bd211239ab8b06e933dff51471b4f4df1fe9d268602552f1062eb6e93737d

PubMed: 25486415
Pub PDF: PDF icon 25486415.pdf

Abstract
OBJECTIVE:
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).

DESIGN AND METHODS: We prospectively evaluated T-cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n = 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.

RESULTS: Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DRCD45ROCD4, CCR5CD4, OX40CD4, and Fas effector memory CD8 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 and Fas effector memory CD4 T-cell frequencies significantly expanded, and central memory CD4 T-cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, effector memory/central memory CD4 T-cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients.

CONCLUSIONS: 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 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.

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Citation:

Haridas V, Pean P, Jasenosky LD, Madec Y, Laureillard D, Sok T, Sath S, Borand L, Marcy O, Chan S, Tsitsikov E, Delfraissy JF, Blanc FX, Goldfeld AE; CAPRI-T (ANRS 12164) Study Team. TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB. AIDS. 2015 Jan 28;29(3):263-73. doi: 10.1097/QAD.0000000000000546. PubMed PMID: 25486415.