TY - JOUR
T1 - Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis
AU - CORTIS Study Team
AU - Mulenga, Humphrey
AU - Musvosvi, Munyaradzi
AU - Mendelsohn, Simon C
AU - Penn-Nicholson, Adam
AU - Kimbung Mbandi, Stanley
AU - Gartland, Andrew-Fiore
AU - Tameris, Michèle
AU - Mabwe, Simbarashe
AU - Africa, Hadn
AU - Bilek, Nicole
AU - Kafaar, Fazlin
AU - Khader, Shabaana A
AU - Carstens, Balie
AU - Hadley, Katie
AU - Hikuam, Chris
AU - Erasmus, Mzwandile
AU - Jaxa, Lungisa
AU - Raphela, Rodney
AU - Nombida, Onke
AU - Kaskar, Masooda
AU - Nicol, Mark P
AU - Mbhele, Slindile
AU - Van Heerden, Judi
AU - Innes, Craig
AU - Brumskine, William
AU - Hiemstra, Andriëtte
AU - Malherbe, Stephanus T
AU - Hassan-Moosa, Razia
AU - Walzl, Gerhard
AU - Naidoo, Kogieleum
AU - Churchyard, Gavin
AU - Hatherill, Mark
AU - Scriba, Thomas J
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Objectives 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 (https://creativecommons.org/licenses/by/4.0/).
AB - Objectives 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 (https://creativecommons.org/licenses/by/4.0/).
U2 - 10.1164/rccm.202103-0548OC
DO - 10.1164/rccm.202103-0548OC
M3 - Article
C2 - 34520313
SN - 1073-449X
VL - 204
SP - 1463
EP - 1472
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 12
ER -
