1. Evidence for use of urinary LAM
Dr Tom Boyles
University of the Witwatersrand, Johannesburg, South Africa
With thanks to Ankur Gupta-Wright for slides from STAMP trial
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2. Conflicts of interest Alere now Abbott-
Speaker fees for academic meetings
Donation of LAM strips
Lending of equipment for studies
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3. The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018

4. Significant morbidity and mortality from HIV/TB
0.4 million deaths in 20161
TB causes 32-67% deaths in HIV+ adults admitted to hospital in Africa2
Half undiagnosed at time of death2
Urine-diagnostics have good diagnostic yield3
Urine easily obtained
Disseminated TB common in advanced HIV
Global Tuberculosis Report 2017
Gupta et al, AIDS Systematic Review and Meta-Analysis of PM studies
Lawn et al, BMC Med 2015 & BMC Med Observational study
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5. We don’t do
If no one does it skip
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7. Costs and training Costs Cost savings Training $3 per test
Less other investigations e.g. ultrasound scans
Training
Debate regarding use at bedside or by referral to laboratory services
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8. How to test a test Diagnostic intervention research
Test research
Diagnostic research
Diagnostic intervention research
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9. The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018

10. The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018

11. P = Adults suspected of having TB I = Urine LAM C = Xpert/nothing
O = Morbidity and mortality
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12. Pooled sensitivity 44% Pooled specificity 92%
All patients with HIV
Pooled sensitivity 44% Pooled specificity 92%
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13. Pooled sensitivity 54% Pooled specificity 90%
Inpatients with HIV
Pooled sensitivity 54% Pooled specificity 90%
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14. Pooled sensitivity 21% Pooled specificity 97%
Outpatients with HIV
Pooled sensitivity 21% Pooled specificity 97%
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15. Pooled sensitivity 49% Pooled specificity 90%
CD4 <200
Pooled sensitivity 49% Pooled specificity 90%
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16. Pooled sensitivity 56% Pooled specificity 90%
CD4 <100
Pooled sensitivity 56% Pooled specificity 90%
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20. A note on specificity Possible cross reactivity with NTM
Higher specificity with more reference samples and composite reference standards
Nel 19/21 patients with confirmed NTM but no evidence of TB were LAM +ve
Low cross reactivity found in patients with CF who had NTM of the lung
Lawn >99% specificity when using multiple samples and composite reference standard
Nel et al CID 2017
Lawn et al BMC Med 2017
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21. Current WHO guidance 1- LAM not to be used except as below
2- LAM may be use in HIV positive adult inpatients with
Signs and symptoms of TB with CD4 count <100
If seriously ill regardless of CD4 count
With unknown CD4 count
(conditional recommendation, low quality evidence)
WHO consolidated guideline 2016
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22. What’s new since ?
Nel 19/21 patients with confirmed NTM but no evidence of TB were LAM +ve
Low cross reactivity found in patients with CF who had NTM of the lung
Lawn >99% specificity when using multiple samples and composite reference standard
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23. We identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44 %) tested positive for urinary LAM
Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB.
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24. How to test a test Diagnostic intervention research
Test research
Diagnostic research
Diagnostic intervention research
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26. Patients with HIV needing admission
Randomised to routine diagnostics +/- LAM
2500 patients in 4 countries
Median CD4– 84
Primary outcomes = 8 week mortality
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27. NNT 25
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28. on behalf of the STAMP trial team
Rapid urine-based screening for TB to reduce AIDS-related mortality in hospitalized patients in Africa (STAMP) trial
Ankur Gupta-Wright, Elizabeth L Corbett, Joep J van Oosterhout, Doug Wilson, Daniel Grint, Melanie Alufandika, Jurgens A Peters, Lingstone Chiume, Stephen D Lawn & Katherine Fielding
on behalf of the STAMP trial team
CROI 2018
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29. 2600 UNSELECTED adult HIV+ admissions
Edendale, KZN, South Africa
2600 UNSELECTED adult HIV+ admissions
Irrespective of TB symptoms
Exclude:
<18 years old
TB treatment in last 12 months
IPT in last 6 months
Outside follow-up area
Admitted >48 hours
Unable to provide consent
Zomba, Malawi
Standard of care arm
Sputum Xpert MTB/RIF
Intervention arm
Sputum Xpert MTB/RIF +
Urine TB-LAM and Xpert MTB/RIF +
CROI 2018
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30. Unselected HIV +ve admissions 90% at least 1 TB symptom 85% on ART
CD4 215
11.5% had TB
CROI 2018
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31. CROI 2018
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32. Microbiologically confirmed TB, intervention arm (n=210)
Samples submitted for TB testing:
99.0% produced urine
56.9% produced sputum
14.3% (n=30)
Sputum Xpert (n=85)
8.6% (n=18)
13.8% (n=29)
3.8% (n=8)
41.4% (n=87)
Urine LAM (n=158)
6.2% (n=13)
11.4% (n=24)
Urine Xpert (n= 74)
Note: 1 patient was negative on all Xpert and LAM tests but was sputum TB culture positive
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33. Diagnostic accuracy, incremental yield and cost of determine TB-LAM and sputum induction for in seriously ill adults with HIV, cough and WHO danger signs
Tom H Boyles1, Rulan Griesel2, Annemie Stewart2,
Marc Mendelson1, Gary Maartens2
1Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, South Africa
2 Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa
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34. Cough and WHO danger signs CD4 107 50% had TB
325 HIV +ve admissions
Cough and WHO danger signs
CD4 107
50% had TB
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35. $50
$42
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37. Summary Cheap Point of care Identifies sick patients with TB
2 RCTs show mortality benefit
May be cost saving
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