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Blood RNA biomarkers for tuberculosis screening in people living with HIV prior to anti-retroviral therapy initiation: A diagnostic accuracy study.

Tiffeney MannRishi K GuptaByron Wp ReeveGcobisa NdlangalavuAneesh ChandranAmirtha P KrishnaClaire Jacqueline CalderwoodHappy TshivhulaZaida PalmerSelisha NaidooDesiree L MbuGrant TheronMahdad Noursadeghi
Published in: medRxiv : the preprint server for health sciences (2023)
Our data demonstrate that blood RNA biomarkers do not perform any better than CRP as triage tests for TB among PLHIV prior to ART initiation. Since CRP is already widely available on a low cost point-of-care platform, our findings support further evaluation of the clinical and health-economic impact of CRP-based triage for pre-ART TB screening. An underlying mechanism that limits the diagnostic accuracy of RNA biomarkers for TB among PLHIV prior to ART may be upregulation of interferon signalling in untreated HIV. Since interferon activity underpins upregulated expression of TB biomarker genes, HIV-induced upregulation of interferon-stimulated genes may reduce the specificity of blood transcriptomic biomarkers for TB in this context. These findings highlight a wider need to identify interferon-independent host-response based biomarkers to support disease specific screening of PLHIV pre-ART initiation.
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