• The Journal of infection · Apr 2014

    Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy.

    • Denise C Hsu, Stephen J Kerr, Parawee Thongpaeng, Thatri Iampornsin, Sarah L Pett, John J Zaunders, Anchalee Avihingsanon, Sasiwimol Ubolyam, Jintanat Ananworanich, Anthony D Kelleher, and David A Cooper.
    • The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Electronic address: d.hsu@amr.org.au.
    • J. Infect. 2014 Apr 1;68(4):344-54.

    ObjectivesDespite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.MethodsHIV-infected, ART-naive Thai adults with CD4 T cell count ≤350 cells/μL starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.ResultsFifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/μL and plasma HIV-viral-load 4.9log10 copies/mL. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count <100 cells/μL was less (P = 0.005) and TB-sensitisation was more likely (P = 0.013) to be associated with positive baseline PPD-Sp-CD4 response. At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P = 0.017) in patients not classified as TB-sensitised. The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.ConclusionsRestoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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