HIV-NAT: Promoting clinical research and rational use of antiretroviral agents in Thailand

1. HIV-NAT: Promoting clinical research and rational use of antiretroviral agents in Thailand

2. ART access in resource limited settings • AIDS progression and mortality in less-developed countries continues to rise • Causes: • Access to antiretroviral therapy (ART) • Poor access to voluntary counselling and testing • Limited public health infrastructure to support diagnosis and monitoring • Lack of trained staff to deliver services

3. HIV-NAT History • HIV-Netherlands-Australia-Thailand Research collaboration established 1996 • Aims: • to conduct clinical research into ART • to develop and promote appropriate and affordable treatment strategies for people with HIV in Thailand and neighbouring countries

4. Research questions in resource limited settings • Can ‘state of the art’ clinical trials be successfully conducted? • Can HIV disease progression be retarded to the same degree as achieved in developed countries? • Can strategies be developed to maintain ART for clinical trial participants after the trials have ended? • How can a clinical research network successfully build local capacity and inform local policy development? • Are intensive monitoring strategies required in settings with considerable economic constraints?

5. HIV-NAT Trials • HIV-NAT trials have been consistent with Thai National treatment guidelines • Clinic visits are conducted at least 3 monthly: • history and physical examination, assessments of disease progression and ART toxicity • Blood collection for immunological, virological, haematological and biochemical tests • Adherence counselling • Early protocols HIV-NAT initiated • Subsequently participated in multicentre trials

6. Pediatric studies 1996 1997 1998 1999 2000 2001 2002 2003 2004 Prepared by John Liddy, HIV-NAT HIV-NAT drug fund NNRTI failure 015 STUDY TIMELINES at HIV-NAT 014 013 Adult studies 012 SPD 011 HIV-NAT 006 Completed studies STACCATO HIV-NAT 010 HIV-NAT 009 d4T ER Atazanavir HIV-NAT 005 004 Vanguard ESPRIT T-20 PK HIV/Hep B/C 2NN Decadurabolin 007 003 series 002 series 001 series March 2004

7. HIV-NAT outcomes (1) • Process measures (March 2004): • 20 trials completed, 14 in progress • >1,500 currently enrolled & post-trial patients receiving ART • Two year retention rates on clinical trials are greater than 90% • Clinical Outcome measures – 001- 005 series of trials • Median time to follow up: 62.3 months • 29 of 417 patients progressed to AIDS or died • TB most common event defining progression • Outcomes equivalent to or better than developed world cohorts

8. HIV-NAT outcomes (2) • HIV-NAT drug – subsidized ART on a sliding scale • Capacity and infrastructure building • Laboratory practice • Clinical practice • Health personnel training • Influence on local policy development

9. WHO 3 by 5 initiative • Treatment gap declared a global emergency in September 2003; WHO and UNAIDS launch 3 by 5 initiative • Target: 3 million people on ART by 2005 • Aim: universal access to treatment as a human right

10. 3x5 Pillar 5 • ‘As treatment programmes go to scale, it is critical to derive data about what works, and what does not work, and why, as fast as possible’ • Pillar 5 • Build on successes • The rapid identification and re-application of new knowledge and successes (operational research (OR) agenda)

11. 3x5 Operational Research Agenda • Coordinate and help develop an appropriate operational research agenda relevant to needs of ART programmes • Seek data on the impact of scaling up ART on prevention and at risk behaviour; on mitigation; on stigma and discrimination

12. 3x5 OR agenda (2) • To identify ways to define the externalities of ART scale-up on health systems performance • To identify ways to cost ART programmes and to link costs to impact and effectiveness

13. 3x5 OR agenda (3) • To improve programme design and find better tools to reduce risky behaviour, the evolution of drug resistance, based on the analysis of data • To incorporate new knowledge rapidly back into ART programme policy and practice

14. HIV-NAT Summary • HIV-NAT is a successful clinical research network, providing: • Access to ART • Appropriate clinical care • Good health outcomes • High degree of medication adherence • Local capacity and expertise • Improved public health infrastructure

15. HIV-NAT policy implications (1) • Rational drug use (RDU): • right drug, right patient, right indication, right dose, right duration, lowest cost • HIV-NAT demonstrates that RDU can be realised and good clinical outcomes can be achieved in resource-limited settings if funding and resources are available

16. HIV-NAT policy implications (2) • Challenge for the international community to contribute funds, training and resources so that • Work in resource limited settings can continue • ART can be delivered in a rational and coordinated manner • Programmes can be implemented and broadened to reduce morbidity and ultimately save lives

17. Authors/Acknowledgements • Dr Stephen Kerr • Dr Chris Duncombe • Theshinee Chuenyam • Prof Kiat Ruxrungtham • Prof Joep Lange • Prof David Cooper • Prof Praphan Phanuphak • HIV-NAT staff The HIV-Netherlands Australia Thailand Research Collaboration (HIV-NAT) 104 Rajdumri Road Pathumwan, Bangkok 10330 Thailand Email: Chris.d@chula.ac.th