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Simon Mendelsohn (cohort 2015-16) co-authored this article.

We evaluated longitudinal kinetics of an 11-gene blood transcriptomic tuberculosis (TB) signature, RISK11, and effects of TB preventative therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11+ participants were randomised to TPT or no TPT; RISK11- participants received no TPT. PLHIV received standard-of-care ART and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by RT-qPCR. Measurements and Main Results RISK11+ status was transient in most of the 128 HIV-negative participants with longitudinal samples; >70% of RISK11+ participants reverted to RISK11- by 3 months, irrespective of TPT. By comparison, reversion from a RISK11-positive state was less common in 645 PLHIV (42.1%). Non-HIV viral and non-tuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%), than those with bacterial organisms other than TB (13.4%), or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Conclusions Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (


Visit the American Journal of Respiratory and Critical Care Medicine to read the full article.