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

Objectives: Despite 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. Methods: HIV-infected, ART-naive Thai adults with CD4 T cell count <= 350 cells/mu L 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. Results: Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/mu L and plasma HIV-viral-load 4.9log10 copies/ mu L. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count < 100 cells/mu L 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. Conclusions: Restoration 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. (c) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.