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4/13/2011
1
Dr Nick PatonMRC Clinical Trials Unit, London
17TH ANNUAL CONFERENCE OF THE
BRITISH HIV ASSOCIATION (BHIVA)
6-8 April 2011, Bournemouth International Centre
Tuberculosis:New drugs and diagnostic
approaches – at last Nick Paton MD FRCP
MRC CTU, London
4/13/2011
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MRC adult HIV trials portfolio • Optimising treatment in early chronic HIV disease
– Early antiretroviral therapy – Hydroxychloroquine / anti-inflammatory therapy
• Optimising first-line therapy– Protease inhibitor monotherapy – Raltegravir-based dual therapy– Third drug class + nutrition + OI prophylaxis
• Optimising second-line therapy– Raltegravir-based dual therapy / PI monotherapy
• Co-infections– Tuberculosis, Hepatitis B, Hepatitis C
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MRC’s role in TB treatment trials
1948-86
Tuberculosis
Research Unit
1947-48
Streptomycin trial
1948: Tuberculosis
Research Unit
1970 1st Trial of
short course
chemotherapy
ReMox, Rifaquin,
STREAM
Austin Bradford Hill Philip D’Arcy Hart
Wallace Fox Denny Mitchison
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MDR-TB in new TB cases
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XDR-TB Survival
Gandhi Lancet 2006; 368; 1554
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(X)XDR-TB
Shah et al; EID 2011, 17, 510-513
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+ SQ109
OPC-67683
etc
TB drugs in clinical development
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Timing of ART
Karim S NEJM 2010
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Biomarkers
• Need TB biomarkers as predictors of reactivation and cure– Use as surrogate endpoint
– Accelerate dose selection trials
– Shorten duration of follow up in clinical trials
2-month sputum culture conversion and TB outcome
Phillips, pers. communication
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TB diagnosis
Boehme NEJM 2009; 363; 1005-15