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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

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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