Impact of Active Tuberculosis on Immune Recovery in HIV-infected Individuals Receiving ART H.Y. Tan 1, Y.K. Yong 1, L.Y. Ong 1, Y.M. Lee 1, S.F.S. Omar 1, S. Shasheela 1, Y.K. Pang 2, A. Kamarulzaman 1 1. Centre of Excellence for Research in AIDS (CERiA), University of Malaya 2. Respiratory Unit, Department of Medicine, University of Malaya Medical Centre Kuala Lumpur, Malaysia

Introduction Immune reconstitution disease (IRD) or immune reconstitution inflammatory syndrome (IRIS) frequently complicates ART treatment particularly in severely immune deficient patients – little is known about the immunopathology of the syndrome – predictive markers have yet to be found

Materials & Methods TB disease Baseline No TB disease worsening No TB disease Post-ART Event No TB disease TB disease TB-IRD (n=7) TBOI (n=8) Unmasking-TB (n=6) non-TB, HIV (n=21) - sCD14, IL-18, sTNF-RI and sCD30 of baseline and event were measured using standard ELISA method. - A prospective longitudinal cohort of patients with CD4 <200cells/ul commencing ART was established at UMMC in Samples are collected at baseline and at 5 time points to week 48 of ART. - Additional samples were collected from those who develop symptoms suggestive of IRD or unmasking- TB disease. - From the cohort, 21 HIV-patients with TB disease either at baseline or developed soon after initiation of ART were recruited into this study. -Each case was matched with one non-TB, HIV patients similar in age, baseline plasma viral load and CD4 count. - The patients were divided into 4 groups: case control

Results & Discussions - Significantly high level of baseline sCD14 was seen in both TB-IRD and unmasking-TB patients suggesting that these two adverse events are associated with high baseline bacterial (LPS or LAM) load. - Baseline IL-18 was significantly higher in TB-IRD patient as compared to TBOI patients. - Differences of baseline sTNFRI and sCD30 among the 4 groups of patients were significant.

- Level of sCD14 in TBOI and unmasking-TB were high as compared to TB-IRD and non-TB, HIV patients. - Level of IL-18 in TB-IRD and unmasking-TB patients were significantly higher as compared to TBOI and non-TB, HIV patients suggesting that activation and production of pro-inflammatory cytokine from macrophages may involve in the pathogenesis of these adverse event. - Significantly higher level of sTNFRI was seen in TB-IRD patients as compared to TBOI suggesting Th1 bias. - Significantly higher level of sCD30 was seen in unmasking-TB patients as compared to non-TB, HIV patients suggesting Th2 bias.

Conclusions -Pre-ART sCD14 and IL-18 predict paradoxical TB-IRD and unmasking-TB -both TB-IRD and unmasking-TB event are mediated by innate immunity. -Cytokine environment (Th1/Th2 bias) has an influence to these adverse events.

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