Role of IL-6 as a predictor of Paradoxical TB IRIS in HIV Patients with Pulmonary

TB in a cohort from India Gopalan Narendran, Bruno Andrade, Alan Sher , Sudha Subramanium , Chockalingam Chandrasekhar, Soumya Swaminathan, Irene SeretiAim of Project: Identify clinical and laboratory predictors of

paradoxical TB-IRIS

Intramural NIH to India Grant

Baseline demographics IRIS (n=25) Non-IRIS (n=22)Mean + SDAge (years) 37.7+9.8 36.2+7.2Weight (kgs) 43.4+8.8 42.7+9.6 HB (gms%)* 8.7+1.8 10.4+1.9 HCT(%)** 25.5+5.9 30.0+5.7

Viral load(Log10)copies/ml*** 5.8+0.33 5.2+ 0.91

Median (IQR) CD4 cells/mm3* 93 (39-135) 156 (88-264) CD8 cells/mm3 764(311-1095) 459 (297-727) CD4/CD8 ratio*** 0.10 (0.05-0.18) 0.34 (0.21-0.47)Time to ART *(in days) 20 (14-30) 43 (23-68)

* p <0-05,**p<0.01,*** p<0.001

Cytokine profile

Profile of innate responses –at baseline and at IRIS/M3 IL-6 at baseline and at IRIS/M3

CRP at baseline and at IRIS/M3

Biomarker candidates for HIV-TB IRIS identified in our Cohort study in India

Data from each biomarker represent pre-ART values Data were adjusted by age, time to ART, CD4 count, CD4CD8 ratio, HIV RNA levls

ConclusionParadoxical TB-IRIS among culture positive PTB -caused by activation of both innate and adaptive immune responses • Predictors include high Viral Load, high monocyte count , Low CD4, Low CD4/CD8 Ratio, HCT and HB at baseline •IL-6 levels at baseline poses to be a promising predictor• Combinations of these markers can be useful to predict the disease and could be possible drug targets in future

Barber DL et al.