AIDS Clinical Trials Group ACTG Network: Research Agenda

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AIDS Clinical Trials Group (ACTG)
NetworkResearch Agenda
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ACTG Network Mission

• To develop and conduct scientifically rigorous
  translational and clinical trials research to
• Investigate viral and immune pathogenesis of HIV
  and its complications and co-morbidities
• Evaluate novel drugs and strategies for treating
  HIV infection
• Evaluate interventions to treat and prevent
  HIV-related co-infections and co-morbidities
• Publish and disseminate results that improve
  care, and reduce or eliminate morbidity and
  mortality associated with HIV infection

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ACTG Research Priorities

• Optimizing clinical management of ART and
  co-morbidities (55 effort)
• Translational research and new drug development
  (25 effort)
• Vaccine research (therapeutic vaccines 5-10
  effort)
• Prevention of MTCT (impact of PMTCT regimens on
  ART resistance, ART response in women - 5
  effort)
• Prevention of HIV Infection (5-10 effort)
• Oral HIV/AIDS research (NIDCR)

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Optimizing ART Management Initial and Salvage
ART Regimens

• Studies focused on novel combinations of existing
  drugs and integrating new ARVs and new classes of
  ARVs into effective treatment for all stages of
  HIV disease
• Phase I/II PK and drug interaction studies
• Phase II pilot, dose-ranging, early efficacy
  studies
• Phase IIB/III/IV studies of new drugs, new
  combinations vs standard of care
• Strategy RCTs for optimizing ART for
  treatment-experienced and treatment naïve patients

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Optimizing ART Management in Resource-Limited
Settings

• Investigation of novel initial ART regimens
• Simplifying initial ART
• DOT novel strategies for CD4, HIV RNA
  monitoring
• Studies of novel second line therapies and ART
  strategies for patients failing initial regimens
• Treatment and prevention of complications of ART
• Treatment and prevention of endemic OIs and other
  complications in the context of ART

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Translational Research and Vaccine Development

• Dendritic cell vaccine electroporated with
  autologous virus huCD40L RNA
• Autologous CD4 T cells transduced with VRX496
  (HIV antisense RNA approach)
• Merck Ad-5 gag/pol/nef vaccine in pts with HIV
  RNA lt 50 c/ml on ART
• Collaborative studies with HVTN to identify new
  candidate vaccines and correlates of protection
  that could be studied in HIV-infected individuals

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Optimizing Management of Co-Infections

• Immediate vs delayed ART in patients with active
  TB
• When to start RCT of immediate vs later ART in
  pts with CD4 counts of 350-550 in
  resource-limited countries HPTN 052-ACTG A5245
  collaboration (HIV transmission, TB, serious
  bacterial infections, other OIs, non-AIDS events)
• Novel strategies for treatment, prevention of
  endemic OIs
• New drugs and strategies to maximize SVR and
  minimize liver-related morbidity and mortality in
  HCV-, HBV-coinfection
• Vaccine prevention of HPV-associated anogenital
  and cervical carcinoma (collaboration with
  NCI-AMC, WIHS)

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Optimizing Management of ART Complications
Co-Morbidities

• Targeted mechanism-based interventions
• Lipid/CVD (NHLBI, NCCAM)
• Body fat/glucose metabolism (NCCAM)
• Bone metabolism
• Neurologic (NINDS-NARC)
• Renal
• Hepatic
• Primary prevention by changing ART paradigms

Relative Distribution of Ongoing or Planned
Studies
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PMTCT Impact of Drug Resistance on Future
Treatment Options in Women

• A5208 Optimal Combination Therapy After
  Nevirapine Exposure (OCTANE)
• A5207 (MOMS) 3 ART strategies to reduce NVP
  resistance after intrapartum single dose NVP
• A5190 Evaluation of infants exposed to tenofovir
  and other ARVs in RCTs
• Collaborative studies with IMPAACT Network

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Prevention of HIV Infection

• ACTG research priorities integrated with HPTN
• Joint/collaborative HPTN-ACTG Prevention Science
  Committee
• Proposed studies
• Pooling strategies to identify acutely infected
  patients (HPTN-CHAVI) in international and U.S.
  sites
• Treatment interventions in acutely infected pts
• PREP
• Other prevention for positives

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Unique Strengths of the ACTG

• Broad expertise to conduct research in
  resource-limited international and U.S. settings
• Innovative, highly expert clinical, laboratory
  and statistical investigators
• Highly coordinated administrative infrastructure
• Network of expert CRSs with access to broadly
  representative patient populations
• Strong collaborative community involvement
• Strong collaborative relationships with pharma,
  other networks, NIH institutes, and external
  investigators