Effective combined antiretroviral therapy provides partial immune recovery to mycobacterial antigens in vertically infected, BCG-vaccinated youth living with HIV

Abstract

BackgroundWe assessed the cytokine response by PBMC of youth living with HIV (YLHIV) under combined antiretroviral therapy (cART) to Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (BCG) antigens. MethodsPBMC from 20 Brazilian YLHIV under cART with long-term (≥1 year) virological control, and 20 healthy controls were cultured for 24–96 h under stimulation with BCG, Mtb lysates, ESAT-6 and SEB. We measured TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10 and IL-17 in culture supernatants using a cytometric bead array. ResultsControls had higher IFN-γ production at 24, 48, 72 and 96 h upon stimulation with BCG lysate, plateauing at 48 h (Median = 1991 vs. 733 pg/mL; p = 0.01), and after 48–72 h of stimulation with Mtb lysate, plateauing at 48 h (3838 vs. 2069 pg/mL; p = 0.049). YLHIV had higher TNF-α production at all time points upon stimulation with ESAT-6, with highest concentration at 36 h (388 vs. 145 pg/mL; p = 0.02). Within the YLHIV group, total CD4 T cell count and CD4/CD8 ratio were associated with IFN-γ response to Mtb lysate and ESAT-6, respectively. ConclusionsEven under long-term cART, YLHIV seem to have a suboptimal T-helper-1 response to mycobacterial antigens. This can be explained by early immunodeficiency in vertical infection, with lasting damage.