Alfred Andama

Fellowship Site: Makerere University, Uganda

Us Institution: Yale University

Project Title: Oral swab testing using GeneXpert Ultra for TB screening among PLHIV Background: Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV) worldwide (WHO report, 2019). PLHIV are at an increased risk of TB, and in some African countries, on average 60% of persons with TB have HIV (Dye, 2019). However, identifying active TB in PLHIV poses a diagnostic challenge with the traditional approaches (Candice, 2011). We aim to evaluate the performance of oral swabs to rule-out active TB disease and to facilitate early initiation of TB preventive therapy (TPT).

Rationale: Early confirmation and treatment of active TB is lifesaving for PLHIV while exclusion of active TB is a critical first step in prescribing preventive therapy. This reduces mortality in PLHIV, but has low rates of uptake in most of Sub-Saharan Africa (WHO report, 2020).

Study objectives:

1. To compare the yield of Xpert Ultra testing of material collected from repeated (up to 10 based on prior studies) Copan FLOQswabs among PLHIV with confirmed TB (i.e., positive sputum Xpert Ultra result)

2. To evaluate the sensitivity and specificity of oral swab-based Xpert Ultra testing using the optimal number of Copan FLOQswabs among PLHIV initiating (antiretroviral therapy) ART.

Methods: Leveraging infrastructure from my mentors ongoing NHLBI-funded studies of TB diagnostics in Uganda, we will collect up to 10 oral Copan FLOQswabs from PLHIV initiating ART. We will compare the yield (Aim 1) and accuracy (Aim 2) of Xpert Ultra testing of material from one vs. two Copan FLOQswabs.

Importance of the study: The proposed study will establish a novel method that utilizes the widely available GeneXpert platform and an alternative, simple to collect sample for TB screening to overcome challenges with the current approach to systematic screening for TB among PLHIV. The data will either support larger evaluations of the optimal protocol for oral swab analysis using Xpert Ultra or inform efforts to further refine oral swab analysis using alternative molecular assays. A rapid and sensitive screening tool of this type could result in earlier diagnosis and treatment of TB, facilitate early initiation of TPT, and pave a way for rapid MDR-TB detection in this vulnerable patient population