Finding a cure for HIV initiative
Summary report
June 15, 2012

Background

The CIHR HIV/AIDS Research Initiative has identified that finding a cure for HIV is a high priority for HIV research investments and that this topic will be the focus of new research funding programs. There is also renewed enthusiasm in the international research community that finding a cure for HIV is possible.

For those that have access to treatment, HIV can typically be well managed by current antiretroviral therapies. However, current therapies do not provide a cure and it is necessary for infected individuals to maintain strict adherence to daily treatment in order to control the virus and maintain health. Current treatments do not clear HIV from the body and the virus persists in latent viral reservoirs – ready to replicate should treatment be stopped or become ineffective. Life-long treatment and chronic infection is believed to have negative health implications and there remain the challenges of stigma associated with HIV-positive status for those infected. There are also huge challenges and costs for health care systems trying to deliver effective treatment and care to all those in need. A safe, effective and scalable cure would have enormous benefits for individuals and public health systems around the world.

In July 2012, the International AIDS Society launched a global scientific strategy - Towards an HIV Cure - which was developed by an international scientific working group. The strategy aims to build global consensus on the state of cure research and define the priorities that future research must address in order to tackle HIV persistence in patients on antiretroviral treatment. The goal is to promote better investments in HIV cure research and eventually the successful discovery of a cure.

Canada has extensive expertise in HIV biomedical and clinical research and a number of groups are already investigating issues of HIV persistence. The CIHR HIV/AIDS Research Initiative believes that with enhanced and focused investments, the Canadian HIV research community can contribute significantly to the major scientific challenge of finding a functional and/or sterilizing cure for HIV. On June 15, 2012, CIHR held a consultation meeting with its CIHR HIV/AIDS Research Advisory Committee (CHARAC) and additional Canadian experts on how Canada can best contribute to these efforts and on key aspects of future research funding opportunities (see Appendix 1 for a list of meeting participants).

Towards an HIV Cure

The international scientific strategy1 identifies seven key scientific priorities for HIV cure research:

  1. Determine the cellular and viral mechanisms that maintain HIV persistence during prolonged antiviral therapy and in rare natural controllers.
  2. Determine the tissue and cellular sources of persistent simian immunodeficiency virus (SIV) or HIV in animal models and in individuals on long-term antiretroviral therapy.
  3. Determine the origins of immune activation and inflammation in the presence of antiretroviral therapy and their consequences for HIV or SIV persistence.
  4. Determine host mechanisms that control HIV replication in the absence of therapy.
  5. Study, compare and validate assays to measure persistent HIV infection and to detect latently infected cells.
  6. Develop and test therapeutic agents or immunological strategies to safely eliminate latent infection in animal models and in individuals on antiretroviral therapy. This includes strategies aimed at reversing latency, as well as strategies aimed at clearing latently infected cells.
  7. Develop and test strategies to enhance the capacity of the host immune response to control active viral replication.

Consultation Meeting Recommendations

The meeting commenced with a review of the Towards an HIV Cure strategy, current Canadian cure research and major international efforts in the field. The remainder of the meeting was structured to engage participants in discussing key aspects of future CIHR funding opportunities focused on the priority area of finding a cure for HIV. The following is a summary of the key discussion points and recommendations from the meeting.

Scientific Focus for CIHR Funding Opportunities

Canadian Strengths in HIV cure research and capabilities:

  • Control of immune activation (IL-7, TIM-3)
  • Genome Canada – finding novel cellular host factors that control persistence (genomic as well as proteomics approaches)
  • Humanized mouse models to study HIV latency and T cell development
  • Phenotypic characterization of T-cell subsets
  • Diversity of expertise in HIV basic science, including immunology , virology and cell and molecular biology
  • National clinical trial network (CTN) that can develop Standard Operating Procedures
  • Pilot studies; ability to move rapidly from lab into humans (supported by CTN)
  • Strong community support for translation studies and clinical application of new therapies; community is well organized and coordinated
  • Collaborative approach to research - good contacts with low- and middle-income countries (LMICs)
  • Strong expertise in some directly related fields (outside of HIV) – e.g., epigenetics, transcription, inflammation in general
  • Ability to generate small molecules, expertise in early stage drug development and resources that provide a bridge between academia and pharmaceutical industry (e.g, Centre for Drug Research & Development, which is screening small molecules for reversing latency; also centres in McMaster and Montreal)
  • Proven successful interactions with pharmaceutical and biotechnology industries
  • Rapid access to large patient samples, well characterized cohorts & cell banks in different parts of the country
  • Capacity to perform leukapheresis and freeze large amounts of peripheral blood cells
  • Expertise in gut biopsies

Challenges:

  • Animal models - however, primate facilities do exist in Montreal & Winnipeg (one under development in Quebec), and humanized mouse models available

Areas of IAS Strategy where Canada could best contribute:

  • Could contribute in each of the seven priority areas, difficult to narrow to particular areas
  • Could focus on immunological approaches and functional cure which are not primary focus of current US efforts. Functional cure could be the first step towards the eventual goal of full eradication.
  • Funding opportunity should not exclude any areas of the IAS strategy since they are interlinked

Funding Mechanisms Best Suited to Cure Research

  • There was consensus that the research community needs to be working together – basic scientists with clinicians. A team grant model, or another mechanism that brings people together, is required.
  • There was also some support for catalyst grants, with a particular emphasis on innovation and/or high-risk projects. Also support for continued operating grant priority announcements.
  • In terms of a team grant mechanism, there was some support for funding one large centre or consortium. If 2-3 smaller teams are supported, it was emphasized that the teams should be connected and share information, and that they should not be working on the same issues.

Additional Suggestions

  • Look for opportunities to encourage and support junior investigators
  • Industry involvement will be essential for the translation of research and to provide the research community with access to assays and technologies. Industry involvement should be highly encouraged but perhaps not mandatory as some important lines of research may not be at this stage yet.
  • It will be advantageous for teams to link with international research efforts and this should be encouraged
  • All funding opportunities should stress/mandate innovation
  • Consider requirements for Scientific Advisory Committees, involvement of community and progress reports (to CHARAC)

Next Steps

CIHR and members of the CIHR HIV/AIDS Research Advisory Committee will participate in upcoming events related to the Towards an HIV Cure strategy including participation in the scientific symposium taking place July 19-20, 2012 and Scientific Director participation in the related Stakeholder Advisory Board meeting on July 22, 2012. CIHR will use these opportunities to further develop collaborations and refine plans for future funding opportunities. A summary report of the consultation meeting will be prepared and posted on the CIHR website. The CIHR HIV/AIDS Research Initiative intends to launch funding opportunities related to HIV cure research by the end of 2012.

Meeting Participants

CHARAC Members

  • Jonathan Angel
    Senior Scientist
    Ottawa Hospital Research Institute
    CHARAC Chair
    Cure Initiative, Working Group Member

  • Louise Nadeau
    Professor, Department of Psychology
    Université de Montréal
    CIHR Institute of Neurosciences, Mental Health and Addiction

  • Chris Archibald
    Director, HIV/AIDS Surveillance and Risk Assessment Division
    Public Health Agency of Canada

  • Marc Ouellette
    Scientific Director, CIHR Institute of Infection and Immunity
    Cure Initiative, Working Group Member

  • Eric Cohen
    Professor
    Institut de Recherches Cliniques de Montréal
    Cure Initiative, Working Group Chair

  • Anita Rachlis
    Scientist, Sunnybrook Research Institute
    Ministerial Advisory Council for the Federal Initiative to Address HIV/AIDS in Canada
    Cure Initiative, Working Group Member

  • Marina Klein
    Associate Professor of Medicine
    McGill University

  • Ron Rosenes
    Community representative
    Cure Initiative, Working Group Member

  • Dale McMurchy
    CIHR Institute of Health Services and Policy Research

  • Sean Rourke
    Scientist, Centre for Research on Inner City Health
    St. Michael's Hospital

  • Judy Mill
    Professor, Global Health
    University of Alberta

  • Shari Margolese
    Community representative

Cure Meeting Participants

  • Petronela Ancuta
    Associate Professor, Université de Montréal
    Département de Microbiologie et Immunologie

  • Mario Ostrowski
    Associate Professor, Department of Medicine
    University of Toronto

  • Alan Cochrane
    Professor, Molecular Genetics
    University of Toronto

  • Michel Roger
    Professeur
    Département de microbiologie et immunologie
    Université de Montréal

  • Keith Fowke
    Professor, Department of Medical Microbiology
    University of Manitoba

  • Ivan Sadowski
    Professor, Department of Biochemistry &
    Molecular Biology
    University of British Columbia

  • Anne Gatignol
    Associate Professor, Department of Medicine
    McGill University

CIHR Staff

  • Jennifer Gunning
    Associate Director
    CIHR HIV/AIDS Research Initiative

  • Paula Kirton
    Associate Director
    CIHR HIV/AIDS Research Initiative

  • Jane Hutchison
    Associate
    CIHR HIV/AIDS Research Initiative

  • Simone Marcantonio
    Project Officer
    CIHR HIV/AIDS Research Initiative

  • Jaime Flamenbaum
    Senior Advisor
    CIHR Ethics Office

  • Nancy Mason Maclellan
    Deputy Director
    Targeted Initiatives Branch

Footnotes

Footnote 1

The International AIDS Society Scientific Working Group on HIV Cure, Nature Reviews Immunology 12, 607-614 (August 2012).

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