Transcript Sino-US ACTG

Adult AIDS Clinical Trials
Group International
Therapeutic Initiative
AACTG
• Funded by NIAID/DAIDS (NIH)
• Established in 1986
• Mission: conduct investigator-initiated,
hypothesis-driven and pathogenesis-based
clinical trials of the treatment of HIV
infection and its sequelae
• Approximately 75 multi-center studies
active at any time at 35 US sites
• 2,000 - 3,000 subjects enrolled per year
AACTG International Therapeutic
Clinical Trials Initiative
• Announced late 2001
• Goals:
– Conduct research to elucidate the most effective approaches
to HIV-1 therapy in resource limited international settings
– Transfer technology and develop infrastructure to conduct
clinical trials in resource limited settings
– Support NIAID/DAIDS prevention research efforts (HPTN,
HVTN)
– Accelerate access to state-of-the-art care in resource limited
settings through resource, training and technology transfer
and infrastructure development
– Study the impact of state-of-the-art care and treatment on
persons with HIV-1 infection in resource limited settings
AACTG ICTU Locations
UNAIDS 2001
ACTG A5175
• Partnership with HPTN
• Hypothesis: An all NRTI regimen and a once-daily
regimen are as safe and effective as a standard three
drug, twice-daily regimen of 2 NRTIs and an NNRTI
• Sites: 12 ICTUs in 8 resource-limited countries
• Population: HIV-1-infected persons with < 300 CD4+
cells/L
• Design: Randomized, open-label, 3 arms
• Primary endpoint: plasma HIV RNA
• Duration: 2.5 years
A5175 long-term objectives
• Technology transfer
• Simplified measures for monitoring
efficacy of antiretroviral therapy
A5175 Standard of Care Issues
•
Development of research objectives that
are locally relevant
– Avoid exploitation
– Study design by an international committee
with representatives from each site
– Use ARVs that are/will be available for use in
the countries where the study is conducted
– Priority questions:
1) Evaluation of PI- and NNRTI-sparing regimens
2) Evaluation of once-daily regimens
A5175 Standard of Care Issues
• Post-trial drug access
– Sponsors (NIH, pharmaceutical companies) will
not provide drugs after the study is over
– Standard of care is diverse across the study
sites
– Standard of care is dynamic
– Each site will develop a plan for post-study
ARV access in coordination with local
governmental and non-governmental agencies
A5175 Standard of Care Issues
• Effects of results of studies conducted in
developed countries on study design
– Planned DSMB interim review of A5095 found that
ZDV/3TC/ABC provided inferior HIV suppression
compared to ZDV/3TC/EFV
– Atlantic study found that d4T/3TC/ddI provided inferior
HIV suppression compared to d4T/3TC/NVP
– A5175 team felt it was unethical to randomize
participants to a comparison of ZDV/3TC/ddI with
ZDV/3TC/EFV (or NVP)
– ZDV/3TC/ddI arm removed from the study
A5175 Standard of Care Issues
• Influence of pharmaceutical industry on study
design
– Study is dependent on pharmaceutical companies for
donation of ARVs
– One sponsor will not support study unless the
ZDV/3TC/ddI arm is included
– Scientific objectives of ARV research in developing
countries is being influenced by pharmaceutical
company marketing concerns
– Pharma-independent sources of ARVs are needed for
clinical trials in resource-limited settings