Overview and Research Priorities of the Division of AIDS DAIDS 4th IAS Conference on HIV Pathogenesi

1
Overview and Research Priorities of the Division
of AIDS (DAIDS)4th IAS Conference on HIV
Pathogenesis, Treatment and PreventionJuly 22,
2007

• Mary Fanning, MD, PhD
• Division of AIDS (DAIDS)
• National Institute of Allergy and Infectious
  Diseases
• National Institutes of Health
• U.S. Department of Health and Human Services

2
Mission Statement
The mission of DAIDS is to help ensure an end to
the HIV/AIDS epidemic by increasing basic
knowledge of the pathogenesis and transmission of
HIV, supporting the development of therapies for
HIV infection and its complications, and
supporting the development of vaccines and other
prevention strategies.
3
(No Transcript)
4
Division of AIDS Office of the Director
Office of Program Operations Scientific
Information
Office for Policy in Clinical Research Operations
Pharmaceutical Affairs Branch
Human Subjects Protection Branch
Office of Clinical Site Oversight
Regulatory Affairs Branch
Policy, Training QA Branch
Clinical Research Resources Branch
Basic Sciences Program
Vaccine Research Program
Therapeutics Research Program
Prevention Sciences Program
Pathogenesis Basic Research Branch
Preclinical Research Development Branch
HIV Research Branch
Microbicide Research Branch
Targeted Interventions Branch
Vaccine Clinical Research Branch
Complications Co-infections Research Branch
Prevention Research Branch
Epidemiology Branch
Drug Development Clinical Sciences Branch
Pediatric Medicine Branch
Proposed - April 2007
5
DAIDS Research Programs

• Basic Sciences Program
• Therapeutics Research Program
• Vaccine Research Program
• Prevention Research Program

6
Funding Opportunities

• Cornerstone of AIDS research is the
  investigator-initiated grant
• Other funding opportunities
• Solicitations for specific areas of research
• Opportunities for international investigators
• CFAR, IeDEA, IRID, Multiple PI awards

7
Basic Sciences Program

• Focuses on the fields of pathogenesis, basic
  virology, immunobiology, pathobiology, and the
  discovery of novel therapeutic approaches,
  efficacy evaluation in lentivirus animal models,
  and epidemiology.
• Research Programs
• Multi-Center AIDS Cohort Study (MACS) (1984)
• Womens Interagency HIV Study (WIHS) (1993)
• Centers for AIDS Research (CFARs) (1988)
• NIH AIDS Research Reference Reagent Program
  (1988)
• Integrated Preclinical/Clinical Program (IPCP)
  (1997)
• Pediatric HIV/AIDS Cohort Study (PHACS) (2005)
• International Epidemiologic Databases to Evaluate
  AIDS (IeDEA) (2006)
• Womens HIV Interdisciplinary Network (WHIN)
  (2005)

8
Biology and Transmission Dynamics Priorities

• Mechanisms of HIV entry, genetic variation impact
  on host immunity, HIV ability to replicate and
  cause disease, HIV drug-resistance
• Immune response and regulation factors that
  control HIV or enhance disease progression
• Cell and tissue reservoirs of HIV infection
• Co-factors that promote or prevent HIV
  transmission, disease progression and
  co-morbidities
• Identify new targets for HIV therapeutics,
  vaccines and non-vaccine approaches

9
Epidemiology Priorities

• Understand the changing patterns of the HIV/AIDS
  pandemic globally natural history, clinical
  manifestations, complications of HIV and changes
  in the virus
• Define differences in susceptibility of HIV
  infection, development of HIV disease and
  response to therapy
• Assess impact of therapy, vaccines and other
  interventions on short-, medium-, and long-term
  survival

10
Centers for AIDS Research

• CFAR mission
• To support a multi-disciplinary environment that
  promotes basic, clinical, epidemiologic,
  behavioral, and translational research in the
  prevention, detection, and treatment of HIV
  infection and AIDS.

11
Centers for AIDS ResearchMission

• The CFARs accomplish this mission by
• Providing scientific leadership and institutional
  infrastructure dedicated to AIDS research
• Stimulating scientific collaboration in
  interdisciplinary and translational research
• Promoting development of sustainable
  multidisciplinary HIV/AIDS research programs at
  each CFAR institution
• Strengthening capacity for HIV/AIDS research in
  developing countries
• Sponsoring training and education
• Promoting and supporting innovative HIH HIV/AIDS
  research initiatives

12
Centers for AIDS Research
13
(No Transcript)
14
International epidemiologic Databases to Evaluate
AIDS (IeDEA)

• International regional centers for the collection
  and harmonization of data
• International research consortium to address
  unique and evolving research questions in
  HIV/AIDS currently unanswerable by single
  cohorts.
• This initiative provides a means to establish and
  implement methodology to effectively pool the
  collected datathus providing a cost effective
  means of generating large data sets to address
  the high priority research questions.

15
IeDEA

• Large observational datasets in diverse
  populations
• Impact of HAART Adult and pediatric
• Treated history of HIV
• Outcomes in sub-populations children and
  orphans
• Rare outcomes in long-term HAART therapy (cancer)
• Toxicities of HAART, some rare, will require data
  on HIV negatives to get population norms
• Resistance to ARVs
• Regional impact of prevention strategies

16
IeDEA Participating Regions

17
Therapeutics Research Program

• Develops and oversees RD of therapies against
  HIV disease, including associated opportunistic
  infections (OI), co-infections and complications
  of AIDS in adults, infants, children, and
  adolescents.
• Current Clinical Trials Networks
• AIDS Clinical Trials Group (ACTG) (2006)
• International Maternal Pediatric Adolescent AIDS
  Clinical Trials (IMPAACT) (2006)
• International Network for Strategic initiatives
  in Global HIV Trials (INSIGHT) (2006)

18
Therapeutics Priorities

• Develop new or improved treatments based on novel
  target or utilizing new technologies
• Optimize safety, adherence, resistance and
  durability of response of available therapies by
  testing new formulations, dosing regimes, routes
  of administration and combinations
• Develop new delivery systems and formulations for
  infants, children and adolescents

19
Therapeutics Priorities

• Define effective regimens and treatment
  strategies for individuals with drug-resistant
  HIV
• Develop new interventions to prevent and treat
  co-infections especially TB
• Develop and evaluate therapeutic approaches to
  enhance, restore and/or maintain the immune
  systems of HIV-infected individuals

20
Vaccine Research Program

• Supports the discovery and development of
  vaccines to prevent HIV infection and AIDS
• Current Networks
• The HIV Vaccine Trials Network (HVTN) (2006)
• Research Programs
• Innovation Grants for HIV Vaccines (1997)
• HIV Research Design (HIVRAD) (1998)
• Integrated Preclinical/Clinical AIDS Vaccine
  Development Program (IPACVD) (1997)
• HIV Vaccine Design and Development Teams (2000)
• Center for HIV/AIDS Vaccine Immunology (CHAVI)
  (2005)
• NIAID Vaccine Immune T-cell and Antibody
  Laboratory (N-VITAL) (2007)

21
Vaccine Research Priorities

• Design new or improved vaccine candidates and
  develop new vaccine vectors, adjuvants and
  cytokines that stimulate more potent and durable
  immune responses
• Develop and standardize assays and create animal
  models to support vaccine development
• Evaluate safety, immunogenicity and efficacy of
  HIV vaccine candidates

22
HIV Prevention Research

• Supports the discovery and development of
  microbicides and other biomedical and behavioral
  interventions to prevent HIV infection and AIDS.
• Current Networks
• The HIV Prevention Trials Network (HPTN) (2006)
• Microbicides Trials Network (MTN) (2006)
• Research Programs
• Integrated Preclinical/Clinical Program for HIV
  Topical Microbicides (2001)
• Microbicide Design and Development Teams (2005)
• Microbicide Innovation Program (2006)

23
Prevention Research Priorities

• Identify, develop and test topical microbicides
• Develop additional strategies for prevention of
  mother-to-child transmission
• Assess pre- and post-exposure prophylaxis (ARV
  and immune based) to reduce HIV transmission
• Encourage further development and evaluation of
  behavioral interventions and communication
  strategies to reduce high-risk behavior
  associated with HIV transmission
• Evaluate the long-term impact of male
  circumcision on reducing HIV transmission
• Intervention Strategies for Injection and
  Non-injection Drug Users to Reduce the Risk of
  HIV and Other STIs
• Prevention research is conducted in collaboration
  with other Institutes at NIH NICHD, NIDA and
  NIMH

24
Leadership for HIV/AIDS Clinical Trials Networks
Translational Research / Drug Development ACTG,
IMPAACT
Microbicides MTN
Mother to Child Transmission IMPAACT
HIV Vaccines HVTN
Optimization of Clinical Management
including Co-Morbidities ACTG, IMPAACT, INSIGHT
Prevention of HIV Infection HPTN, HVTN
Populations
25
International Research in Infectious Diseases
(IRID)

• Conduct preliminary or pilot studies or
• Explore the feasibility and initiate the planning
  of collaborative infectious diseases research
  among investigators and institutions
• At international sites where NIAID has
  significant investment in research and/or
  infrastructure

26
International Research in Infectious Diseases
(IRID)

• Areas of Interest
• Research on infectious diseases, e.g. HIV/AIDS
  and HIV co-infections
• Development of immunological, microbiological,
  biostatistical, epidemiological, and clinical
  research capacity is encouraged.

27
Useful Websites

• NIAID, Division of AIDS
• http//www3.niaid.nih.gov/about/organization/daids
  /default.htm
• NIH Funding Opportunities
• http//grants1.nih.gov/grants/index.cfm
• AIDS Info
• http//aidsinfo.nih.gov/

28
HIV Vaccine Research Coordination and
Collaboration

• Global HIV Vaccine Enterprise (2004) - A virtual
  consortium of independent organizations committed
  to accelerating the development of a preventive
  vaccine for HIV/AIDS
• Implementation of a shared strategic scientific
  plan
• Mobilization of additional resources
• Increased collaboration among HIV vaccine
  researchers worldwide
• Partnership for AIDS Vaccine Evaluation (PAVE)
  (2003)
• Voluntary consortium of U.S. government agencies
  and key U.S. government-funded organizations
  involved in the development and evaluation of
  HIV/AIDS preventive vaccines and the conduct of
  HIV vaccine clinical trials

29
HIV Vaccine Research Coordination and
Collaboration

• Center for HIV/AIDS Vaccine Immunology (CHAVI)
  (2005)
• Significant component of the Global HIV Vaccine
  Enterprise
• Developing a more comprehensive understanding of
  the viral and immunological events and host
  genetic factors associated with HIV transmission,
  infection and (partial) containment of virus
  replication
• Testing novel HIV-1 vectors, immunogens and
  adjuvants that suppress viral replication and
  elicit persistent mucosal and/or systemic immune
  responses in animal and human models
• Using SIV infection in primates as a model for
  HIV infection in humans and determine the factors
  that lead to protection from SIV in primates
• Moving potential HIV-1 vaccine candidates into
  phase I clinical trials
• NIAID Vaccine Immune T-cell and Antibody
  Laboratory (N-VITAL) (2007)
• Provide centralized, state-of-the art
  immunogencity testing across all NIAID-sponsored
  HIV vaccine projects
• Facilitate technology transfer from
  NIAID-supported labs to other labs
• Provide quality assurance and quality control for
  all NIAID-supported HIV immunology labs