International Mentored Scientist Award

Potential for Xpert MTB/RIF Ultra cycle threshold values to monitor early response to anti-TB treatment in HIV co-infected patients on antiretroviral therapy

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Despite steady improvements over time, TB treatment success rate remains lower among HIV-coinfected patients (77%) compared to 86% of the general TB population globally. Successful treatment of TB in HIV co-infected individuals is limited by varying levels of immunosuppression, drug-drug interactions, increased pill burden, in addition to a poor quality of life in the psychological domain. It is challenging to direct individualized treatment plans and improve TB treatment outcomes in this population because of the lack of tools to effectively monitor anti-TB therapy in HIV co-infected patients, especially in resource-limited settings. Currently, the conventional method of measuring TB treatment response is sputum smear microscopy, but many people living with HIV have smear-negative TB at baseline because bacillary load reduces with increasing level of immunosuppression. Sputum cultures are also rarely obtained in resource-limited settings because of a lack of specialized laboratories. Cultures are also generally limited by contamination from other fast-growing bacteria, and long turnaround times which increases loss to follow-up. However, we recently demonstrated that baseline sputum Xpert MTB/RIF Cycle Threshold (ct) values, a semi-quantitative measurement of bacterial load by the GeneXpert test, predicts two-month sputum culture status in HIV co-infected patients. We propose to further explore this method using a newer version of the GeneXpert test (Xpert MTB/RIF Ultra) with higher sensitivity and carry out intensive monitoring of early treatment response using Xpert Ultra ct values. Since two-month sputum culture is a widely accepted marker of TB treatment outcome, we want to determine if Xpert ct values from sputum collected at different time points during the first 8 weeks of treatment, predict two-month sputum culture status, in a longitudinal cohort of HIV-infected individuals being investigated for HIV-associated pneumonias in Uganda.