Adult AIDS Clinical Trials Group International Therapeutic Initiative

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Adult AIDS Clinical Trials Group International
Therapeutic Initiative
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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

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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

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AACTG ICTU Locations
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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 lt 300
  CD4 cells/?L
• Design Randomized, open-label, 3 arms
• Primary endpoint plasma HIV RNA
• Duration 2.5 years

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A5175 long-term objectives

• Technology transfer
• Simplified measures for monitoring efficacy of
  antiretroviral therapy

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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
• Evaluation of PI- and NNRTI-sparing regimens
• Evaluation of once-daily regimens

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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

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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

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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