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

Background: We 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. Methods: PBMC 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-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-10 and IL-17 in culture supernatants using a cytometric bead array. Results: Controls had higher IFN-gamma production at 24, 48, 72 and 96 h upon stimulation with BCG lysate, plateauing at 48 h (Median = 1991 vs. 733 mu g/mL; p = 0.01), and after 48-72 h of stimulation with Mtb lysate, plateauing at 48 h (3838 vs. 2069 mu g/mL; p = 0.049). YLHIV had higher TNF-alpha production at all time points upon stimulation with ESAT-6, with highest concentration at 36 h (388 vs. 145 mu g/mL; p = 0.02). Within the YLHIV group, total CD4 T cell count and CD4/CD8 ratio were associated with IFN-gamma response to Mtb lysate and ESAT-6, respectively. Conclusions: Even 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.