Background:
People living with advanced HIV (CD4 < 50 $cells/\mu L$) face a disproportionately high risk of tuberculosis (TB) and early mortality within the first year of starting antiretroviral therapy (ART). Current TB screening methods often fail to detect incipient or subclinical infections in this severely immunosuppressed population. Identifying simple, parsimonious inflammatory biomarkers could provide a critical tool for risk stratification and the development of targeted interventions.
Abstract:
Methods: A case-cohort study ($n=257$) was nested within the REMEMBER randomized trial, which enrolled 850 HIV-positive participants with CD4 < 50 $cells/\mu L$ from ten countries. We evaluated 26 plasma biomarkers using multiplexed immunoassays to identify profiles predictive of incident TB or all-cause death within 48 weeks of ART initiation.
Results: Incident TB occurred in 6.1% of participants, and 5.5% died. A parsimonious 6-biomarker signature (CXCL10, IL-1$\beta$, IL-10, sCD14, TNF-$\alpha$, and TNF-$\beta$) was developed using cross-validation. This signature predicted incident TB with a sensitivity of 0.90 (95% CI: 0.87–0.94) and an AUC of 0.81 (95% CI: 0.78–0.83). While biomarkers associated with TB often declined after ART, those associated with mortality remained persistently elevated.
Conclusion: In advanced HIV, a baseline 6-biomarker inflammatory signature can accurately predict the risk of developing active TB despite screening and preventive therapy. This tool may help clinicians select high-risk patients for intensified monitoring or novel therapeutic strategies.
Keywords: tuberculosis, biomarker, antiretroviral therapy, early mortality.
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- Data de Publicação: 27/11/2019
- Autores: Yukari C. Manabe1 , Bruno B. Andrade2,3,4 , Nikhil Gupte1,5 , Samantha Leong6 , Manisha Kintali6 , Mitch Matoga7 , Cynthia Riviere8 , Wadzanai Sameneka9 , Javier R. Lama10 , Kogieleum Naidoo11,12, Yue Zhao13, W. Evan Johnson13, Jerrold J. Ellner6 , Mina C. Hosseinipour7,14, Gregory P. Bisson15, Padmini Salgame6 , Amita Gupta1 for the ACTG A5274 REMEMBER and NWCS 408 Study Team
