840. Clinical characteristics and serologic biomarkers associated with TB relapse and death in HIV/TB co-infected persons
Session: Oral Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011: 9:15 AM
Room: 156ABC
Background: Readily obtainable biomarkers which reflect disease severity and predict response to TB therapy in HIV/ TB co-infected persons are needed. This study evaluated serologic markers of immune activation along with clinical and radiological characteristics for their association with TB relapse and death in HIV/TB co-infected persons receiving standard TB therapy.

Methods: We analyzed  markers of inflammation in plasma along with demographic, clinical and X-ray data for 182 of 187 evaluable participants in a phase 2, randomized, double-blind, placebo-controlled clinical trial of prednisolone as an adjunct to standard TB therapy in HIV infected persons with smear positive pulmonary TB between October 1998 and 2000. We measured the following markers from stored frozen plasma by multiplex ELISA: TNF-a, sTNFR-I, sTNF-RII, IFN-a, IFN-g, IL-17, IL-7, and the soluble intracellular adhesion molecule (iCAM). Univariate and multivariate models of TB relapse or death used Cox proportional hazard analysis.

Results: There were 29 deaths and 18 relapses that occurred a median of 93 (IQR, [48-139]) weeks after enrollment. There were no differences between the randomized arms, so they were analyzed as one group. At baseline, higher CXR score was associated with male sex, lower BMI, and higher sTNFRI and neopterin levels. In separate multivariable models adjusted for age, sex, baseline CD4 cell count and baseline LVL, higher neopterin (1.3 [1.1-1.6]) and higher IFN-a (1.3 [1.1-1.5]) were each associated with a greater risk of death, while IFN-a (1.3 [1.1-1.5]) was also associated with a higher risk of relapse.

Conclusion: Elevated baseline levels of IFN-a were independently associated with death and relapse in HIV/TB co-infected patients after adjusting for other important correlates; neopterin also was associated with a higher risk of death in HIV/TB co-infected patients who received standard anti-tuberculous therapy but did not receive ART. Further study of these inflammation markers in the context of ART is warranted.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Matifadza Hlatshwayo, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, Christopher Whalen, MD, MS, University of Georgia School of Public Health, Athens, GA, Robert Kalayjian, MD, The MetroHealth Medical Center, Cleveland, OH and Charles Mahan, MD, Cuyahoga County TB Program, Cleveland, OH; MetroHealth Medical Center, Cleveland, OH

Disclosures:

M. Hlatshwayo, None

C. Whalen, None

R. Kalayjian, None

C. Mahan, None

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