LAM Dr Tom Boyles University of the Witwatersrand Johannesburg South Africa The Global Action Fund for Fungal Infections meeting Kampala 1012 April 2018 With thanks to Ankur GuptaWright for slides from STAMP trial ID: 694996
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Slide1
Evidence for use of urinary LAM
Dr Tom BoylesUniversity of the Witwatersrand, Johannesburg, South Africa
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018
With thanks to Ankur Gupta-Wright for slides from STAMP trialSlide2
Conflicts of interest
Alere now Abbott-
Speaker fees for academic meetingsDonation of LAM stripsLending of equipment for studies
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide3
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide4
Significant morbidity and mortality from HIV/TB
0.4 million deaths in 2016
1
TB causes 32-67% deaths in HIV+ adults admitted to hospital in Africa
2
Half undiagnosed at time of death
2
Urine-diagnostics have good diagnostic yield
3
Urine easily obtained
Disseminated TB common in advanced HIV
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018
Global Tuberculosis Report 2017
Gupta et al, AIDS 2015. Systematic Review and Meta-Analysis of PM studies
Lawn et al, BMC Med 2015 & BMC Med 2017. Observational studySlide5
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide6
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide7
Costs and training
Costs$3 per testCost savingsLess other investigations e.g. ultrasound scansTrainingDebate regarding use at bedside or by referral to laboratory services
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide8
How to test a test
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide9
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide10
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide11
P = Adults suspected of having TB
I = Urine LAMC = Xpert/nothing
O = Morbidity and mortality
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide12
Pooled sensitivity 44%
Pooled specificity 92%
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 All patients with HIVSlide13
Pooled sensitivity 54%
Pooled specificity 90%
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Inpatients with HIVSlide14
Pooled sensitivity 21%
Pooled specificity 97%
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Outpatients with HIVSlide15
Pooled sensitivity 49%
Pooled specificity 90%
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 CD4 <200Slide16
Pooled sensitivity 56%
Pooled specificity 90%
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 CD4 <100Slide17
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide18
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide19
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide20
A note on specificity
Possible cross reactivity with NTMHigher specificity with more reference samples and composite reference standards
Nel et al CID 2017Lawn et al BMC Med 2017
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide21
Current WHO guidance
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018
1- LAM not to be used except as below
2- LAM may be use in HIV positive adult inpatients withSigns and symptoms of TB with CD4 count <100If seriously ill regardless of CD4 count With unknown CD4 count (conditional recommendation, low quality evidence)
WHO consolidated guideline 2016Slide22
What’s new since 2016 ?
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide23
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide24
How to test a test
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide25
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide26
Patients with HIV needing admission
Randomised to routine diagnostics +/- LAM2500 patients in 4 countriesMedian CD4– 84Primary outcomes = 8 week mortality
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide27
NNT 25
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide28
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018
Rapid urine-based
s
creening for T
B to reduce
A
IDS-related
m
ortality in hospitalized
p
atients 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 2018Slide29
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018
CROI 2018
Standard of care arm
Sputum
Xpert
MTB/RIF
Intervention arm
Sputum Xpert MTB/RIF
+
Urine TB-LAM and Xpert MTB/RIF
Edendale, KZN, South Africa
Zomba, Malawi
+
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
2600 UNSELECTED adult HIV+ admissions
Irrespective of TB symptomsSlide30
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018
CROI 2018
Unselected HIV +
ve admissions90% at least 1 TB symptom85% on ARTCD4 21511.5% had TBSlide31
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018
CROI 2018Slide32
Sputum Xpert (n=85)
Urine Xpert
(n= 74)
Urine LAM (n=158)
41.4%
(n=87)
14.3%
(n=30)
6.2%
(n=13)
8.6%
(n=18)
3.8%
(n=8)
11.4%
(n=24)
13.8%
(n=29)
Note: 1 patient was negative on all Xpert and LAM tests but was sputum TB culture positive
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018
Microbiologically confirmed TB, intervention arm (n=210)
Samples submitted for TB testing:
99.0% produced urine
56.9% produced sputumSlide33
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 Boyles
1,
Rulan Griesel2, Annemie Stewart
2, Marc Mendelson1, Gary Maartens21Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, South Africa2 Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide34
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018
325 HIV +
ve admissionsCough and WHO danger signs
CD4 10750% had TBSlide35
$50
$42
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018 Slide36
The Global Action Fund for Fungal Infections meeting Kampala 10-12 April 2018 Slide37
Summary
CheapPoint of careIdentifies sick patients with TB2 RCTs show mortality benefitMay be cost saving
The Global Action Fund for Fungal
Infections meeting Kampala 10-12 April 2018