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
IN the developed world progression to AIDS and AIDS-related mortality has fallen dramatically since the mid 1990s, predominantly as a result of highly actice antiretroviral therapy (HAART). ‘
In the less developed world where the burden of HIV/AIDS is greater, access to ART and to good clinical care is poor, and AIDS deaths continue to rise.
Individual socioeconomic circumstances are a clear barrier to access because of the high cost of ART, but there are also structural factors that impede the delivery of ART to people in resource-limited settings. These include poor access to voluntary counselling and testing, limited public health infrsstructure to support diagnosis and monitoring, and a lack of strained 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
The first cases of HIV were noted in Thailand in the 1980’s and when it became apparent that there was a problem, the Thai Government mobilised quickly to promote messages about safe sexual behaviour. Nevertheless, the number of cases continued to rise. It was in this climate that the HIV Netherlands Australia Thailand research collaboration was established in 1996.
How did it happen?
The AIMS of HIV-NAT were to conduct clinical research into ART and to develop and promote affordable treatment strategies for people with HIV iin Thailand and in neighbouring countries.
ART prices decreases in Thailand with the GPO making generic ARV

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?
There were many important questions which needed to be answered about treating HIV in a resource-limited setting. Some of these questions included:
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 strategy required in settings with considerable economic constraints?
Many questions need to be answered (and this also links into the operational research 3x5 agenda stuff)

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
HIV-NAT trials have always been consistent with national treatment guidelines
Clinic visits are conducted at least 3 monthly – and usually more frequently (often monthly). When patients typically move to less frequent visits when they are not on the research arm of a clinical trial, but on maintenance therapy.
At each visit –
Good laboratory practice has been developed by HIV=NAT

6. STUDY TIMELINES at HIV-NAT
Prepared by John Liddy, HIV-NAT
HIV-NAT drug fund
NNRTI failure
015
STUDY TIMELINES at HIV-NAT
014
013
Adult studies
012
SPD
Pediatric studies
011
Completed studies
HIV-NAT 006
STACCATO
HIV-NAT 010
HIV-NAT 009
d4T ER
Atazanavir
HIV-NAT 005
HIV-NAT commenced in 1976
Many studies are conducted both investigator initiated and international multi-centre studies like ESPRIT
ABOUT 1500 patients are on studies at HIV-NAT
ESPRIT enrolled patients from the IL-2 VANGUARD study and from several other HIV-NAT protocols
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 – 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 Capacity and infrastructure building
– 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
How might the work done at HIV-NAT relate to important policy initiaties advocated by WHO?

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
Rational drug use dictates that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements
The rational use of drugs requires that patients receive medicines appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and the community.
HIV-NAT has demonstrated that

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