HIV-Infected Patients Developing Tuberculosis Disease Show Early Changes in the Immune Response to Novel Mycobacterium tuberculosis Antigens

Background: In individuals living with HIV infection the development of tuberculosis (TB) is associated rapid progression from asymptomatic TB to active disease. Sputum-based diagnostic tests for have low sensitivity in minimal and subclinical precluding early diagnosis. The immune response novel Mycobacterium in-vivo expressed latency antigens may help measure stages disease thereby improve diagnosis Methods: Serial prospectively sampled cryopreserved lymphocytes patients Swiss Cohort Study developing (“cases”) matched no (“controls”) were stimulated 10 antigens. Cytokine concentrations measured cases controls at four time points prior TB: T1-T4 T4 being closest point Results: 50 samples nine included. Median CD4 cell count was 289/ul TB-group 456/ul control group. Viral loads suppressed both groups. At Rv2431c-induced Rv3614/15c-induced interferon gamma-induced protein (IP)-10 responses Rv2031c-induced Rv2346/Rv2347c-induced tumor necrosis factor (TNF)-α significantly higher compared ( p < 0.004). T3 - up 2 years TNF-α Area under receiver operating characteristics (AUROC) curves resulted an AUC > 0.92 all antigen-cytokine pairs. Conclusion: vitro -specific HIV-infected that progress toward different those do not TB. These differences precede clinical years, paving way based diagnostics predict stage.