Mentored Scientist Award

In high burden countries, isoniazid preventive therapy (IPT) is recommended for all HIV-infected individuals for whom active TB is deemed unlikely. However confident exclusion of active disease is required prior to initiation of this life-saving intervention. Although the highly sensitive WHO four-part symptom screen effectively rules-out active TB for those who screen-negative, up to two-thirds of HIV-infected individuals screen-positive and are therefore misclassified as ineligible for IPT. For substantial reductions in TB incidence and TB-associated mortality to be achieved, new strategies are needed to improve the selection of HIV-infected individuals for IPT. C-Reactive Protein (CRP), a non-specific inflammatory marker, was shown to be effective in ruling-out active TB among TB suspects in South Africa however its role in determining IPT eligibility in a general population of HIV-infected individuals has not been previously evaluated. The objective of this study is to identify a TB screening algorithm which improves selection of HIV-infected individuals for IPT, beyond that of the currently recommended WHO symptom screen. We will prospectively administer the WHO symptom screen and measure CRP levels using an inexpensive, rapid and easy-to-use point-of-care (POC) assay in 500 HIV-infected adults presenting to an HIV/AIDS clinic in Kampala, Uganda for ART initiation. We will determine the diagnostic accuracy and predictive value of the WHO symptom screen and POC CRP testing for active TB in reference to microbiologic data (Aim 1). We will then identify the optimal TB screening algorithm for determining IPT eligibility by comparing the proportion of HIV-infected adults correctly and incorrectly identified as eligible for IPT (Aim 2). Completion of this pilot study will provide important preliminary data used to plan future studies (K23) which will inform TB screening practices in high burden, resource-poor settings.