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Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography

Abstract

Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

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Figure 1: Radiological and clinical findings in participants with evidence of subclinical pathology (infiltrates, scars or active nodules).
Figure 2: Radiological findings in participants with discrete nodules.

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Acknowledgements

This work was funded by the Wellcome Trust (grant no. 090170 (H.E.) and 104803 (R.J.W.)), the Bill and Melinda Gates Foundation–Wellcome Trust Grand challenges in Global Health (grant no. 37822; D.B.Y.), the US National Institutes of Health (NIH) (grant no. R01 HL106804; J.L.F.) and the intramural research program of the NIH–NIAID (C.E.B.). R.J.W. also received support from the European Union (grant no. FP& HEALTH F3-2012-305578), the National Research Foundation of South Africa (grant no. 96841), the Research Councils of the UK via the Francis Crick Institute (grant no. 10218 and U117565642) and the Medical Research Council of South Africa (Strategic Health Innovations partnership).

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H.E., A.O., C.E.B. and R.J.W. designed the study with input from K.A.W., D.B.Y. and J.L.F.; H.E., T.O. and Q.S.-H. screened participants for study entry; H.E., G.W. and C.F.K. collected samples and data, and provided clinical care for participants during follow-up; J.M.W. led the radiologists and nuclear medicine physicians who reported the [18F]FDG PET–CT scans; K.A.W. and H.E. processed samples; H.E., M.L. and R.P.L. analyzed data with advice and input from R.J.W., K.A.W., C.E.B., J.M.W., A.K.C., C.M.G., A.O. and J.L.F.; R.J.W. supervised data analysis; H.E. and R.J.W. wrote the manuscript, with early input from A.O., C.E.B., D.B.Y., M.L. and J.L.F., and subsequently all authors provided advice and approved the final manuscript.

Corresponding authors

Correspondence to Hanif Esmail or Robert J Wilkinson.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3 and Supplementary Table 1 (PDF 1878 kb)

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Esmail, H., Lai, R., Lesosky, M. et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat Med 22, 1090–1093 (2016). https://doi.org/10.1038/nm.4161

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