Predicting tuberculosis among people living with HIV on antiretroviral treatment in high TB burden settings

Tuberculosis (TB) remains a common opportunistic infection and a major cause of death among people living with HIV (PWH). The aim of this thesis is to evaluate biomarkers that can predict incident TB and to investigate the role of human cytomegalovirus (HCMV) infection in TB disease progression among PWH in high TB and HIV burden settings.
The present thesis begins by showing the incidence of TB among PWH who are on long term antiretroviral therapy (ART) in Thailand. We analyzed data from the HIV cohort with the longest follow-up in Southeast Asia. Then, we provide new evidence that the monocyte to lymphocyte ratio (MLR), a simple biomarker that is available in routine HIV care, can be used to predict the occurrence of TB in PWH. We also validated the MLR in combination with the hemoglobin level to assess TB disease progression in a large international PWH cohort. This thesis also identified the role of the plasma kynurenine to tryptophan (K/T ratio) in predicting TB disease, diagnosis and monitoring treatment response. Lastly, we assessed the role of HCMV infection in the progression of TB disease among virally suppressed PWH.
The results presented here might only apply to high TB and HIV burden settings. Nevertheless, the findings from this thesis have the potential to open up the use of biomarkers that are readily available in routine HIV care and may provide an opportunity to scale up preventive treatment, which has great potential to reduce TB morbidity and mortality in PWH.