Understanding and Intervening Against HIV-associated Tuberculosis

Understanding and Intervening Against HIV-associated Tuberculosis

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This study will evaluate already identified markers of TB disease progression and also identify new markers of TB disease progression from latent to active TB in HIV co-infected patients on cART in Botswana.

A third of the world’s population is infected with Mycobacterium tuberculosis but less than 10% will develop active disease during their lifetime. HIV infected patients on suppressive cART are still at a higher risk of developing active TB. There is therefore a need to identify biomarkers that could identify patients who are at risk of developing active TB so that they can be targeted for TB prevention strategies. In order to halt TB transmission, control efforts need to focus on latent TB infection. Current tests for latency, are not useful as predictors of disease progression. Host biomarkers detected in serum, plasma, saliva and other effusions may be useful as tools for TB diagnosis and monitoring of treatment response.  While most host markers are not specific to TB pathogenesis, a panel of markers associated with Th1-cell activity and IFN-y mediated activity has been identified to be consistently upregulated in patients with confirmed tuberculosis. Transcriptiomic profiling of peripheral blood has also revealed RNA signatures that allow differentiation of active TB from latent TB.

In this study Mupfumi will describe incident TB among patients on cART in Botswana.  As secondary objectives, she will also identify cytokines by different T cells and macrophages that are predictive of development of active TB in HIV patients on cART.