By Richard Jefferys
The research effort to discover a cure for HIV infection continues to gain momentum, with several important developments having occurred since the last issue of TAGline.
In July, the National Institute of Allergy and Infectious Diseases (NIAID) announced the award of three multimillion dollar five-year grants under the aegis of the Martin Delaney Collaboratory, a program named in memory of the longtime AIDS activist and founder of Project Inform, who died in 2009. The awards represent a significant expansion of the original plan, which reflects a number of factors: the commitment of NIAID to the goal of curing HIV; the activism of community-based groups such as TAG, AIDS Policy Project, amfAR, and Project Inform; and the quality of the requests for funding that were submitted by researchers.
Grantees include the Fred Hutchinson Cancer Research Center in Seattle, where coprincipal investigators Keith R. Jerome and Hans-Peter Kiem are overseeing five projects, including a collaboration with Sangamo Biosciences on the use of hematopoietic cell transplants to create HIV-resistant immune cells (Kiem has developed a macaque model for evaluating this type of approach). Jerome is also pursuing the potential use of proteins called endonucleases to excise the HIV genome from latently infected cells.
Principal investigator David Margolis at the University of North Carolina at Chapel Hill is leading the largest of the groups, consisting of 15 scientific projects at nine different academic research centers throughout the U.S. Merck Research Laboratories is a key part of this team, but will not be receiving funding from the National Institutes of Health (NIH). The major goals are to improve the understanding of HIV persistence despite antiretroviral therapy and to develop therapies to target and eliminate viral reservoirs.
Lastly, a triumvirate of principal investigators—Steve Deeks and Mike McCune at University of California, San Francisco, and Rafick-Pierre Sekaly at the Vaccine and Gene Therapy Institute of Florida—are overseeing seven projects aiming to delineate where HIV reservoirs are located in the body and how they are created and maintained, with the ultimate goal of developing therapies that can eliminate reservoirs without causing excessive immune activation.
The announcement of the Martin Delaney Collaboratory grants occurred just a week ahead of the 2011 International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Rome, at which the IAS launched “The Rome Statement for an HIV Cure” calling for an acceleration of cure research. The statement was initiated by members of an IAS Advisory Board working to develop a global scientific strategy for the field, and lists three key objectives:
- Recognizing the importance of developing a safe, accessible, and scalable HIV cure as a therapeutic and preventive strategy against HIV infection and to help control the AIDS epidemic.
- Committing to stimulating international and multidisciplinary research collaborations in the field of HIV cure research.
- Encouraging other stakeholders, international leaders, and organizations to contribute to accelerating HIV cure research through their own initiatives and/or by endorsing this statement and supporting the alliance that the Advisory Board is building.
The online version of the statement currently has 4,479 signatories. You can sign it here: http://www.iasociety.org/Default.aspx?pageId=583. The conference itself offered further evidence of the increased profile of HIV cure research, with multiple sessions and satellite meetings addressing the topic.
Another research funding development came from amfAR, which announced a second round of grants—albeit of far smaller amounts than those bestowed by NIAID—under its amfAR Research Consortium for HIV Eradication (ARCHE) program. The funding will support several scientists who are already part of ARCHE and two new additions to the group: Adriana Andrade at Johns Hopkins and Una O’Doherty at the University of Pennsylvania. Andrade is conducting a small clinical trial of the FDA-approved alcoholism treatment disulfiram (Antabuse), following up on work by ARCHE researcher Bob Siliciano suggesting that the drug might be able to awaken latent HIV reservoirs. O’Doherty plans to compare different approaches to evaluating the size of the HIV reservoir, in hopes of identifying the most accurate and practical methods.
O’Doherty’s study addresses important questions identified at a workshop on cure-related HIV research that took place in Baltimore in April, sponsored by AIDS Policy Project, amfAR, Project Inform, and TAG. A full report and list of recommendations from the workshop will be posted online soon. For a frequently updated list of resources on HIV cure research, including links to articles, scientific papers, and clinical trials, see TAG’s website. The i-Base/TAG 2011 Pipeline Report also contains a section describing the current status of cure-related clinical research, available online.
Finally, a group of community-based organizations sent a letter to the NIH and the U.S. Food and Drug Administration (FDA) asking them to convene a national dialogue on how best to move forward with AIDS cure research. The letter is printed below.
9 August 2011
Jack Whitescarver, Ph.D.
Associate Director for AIDS Research, National Institutes of Health (NIH)
Director, Office of AIDS Research, NIH
Margaret A. Hamburg, M.D.
Commissioner, U.S. Food and Drug Administration (FDA)
The undersigned organizations are writing to request that the NIH and FDA collaborate to convene a workshop on clinical trials and regulatory issues pertaining to HIV cure research. We are keenly interested in anticipating and overcoming obstacles to moving cure research forward at the fastest pace that is justified in the context of both science and safety concerns, and believe that interagency discussions on the subject—perhaps similar to those that have taken place regarding stem cell research—can play a vital role.
At a recent community-sponsored meeting on HIV cure-related clinical research, a number of key issues were identified that we believe could form the basis for a productive, non-product-specific dialogue involving appropriate officials from your two agencies. These include:
- The need for interagency discussions to broaden knowledge and awareness of the current status of HIV cure-related research
- Appropriate pre-clinical milestones to justify advancing approaches into clinical trials
- Evaluating and prioritizing assays with the potential to be used as trial endpoints
- The use of analytical treatment interruptions—and exploration of valid alternatives—to evaluate the effects of interventions, and appropriate parameters for ensuring participant safety
- Methods of improving uptake of gene-modified cells in clinical trials
- Appropriate trial populations for the different types of interventions under consideration
- Facilitating cross-trial comparisons and specimen sharing
- The level of risk that is appropriate for trials where the potential benefits to individual participants may be negligible but the benefits to advancing the science—and therefore to the wider community of HIV-positive people—may be significant
- Ethics and informed consent
- Educational initiatives for institutional review boards and community advisory boards
- The need for government agencies to actively engage the diverse array of stakeholders, including and especially people with HIV/AIDS, in decision-making about research ethics and access to clinical trials
We envision that such a workshop would be the first of an ongoing series of steps to engage the FDA with NIH, researchers, and community representatives in dealing with the regulatory, scientific, and ethical issues related to cure research.
Thank you for your consideration,
AIDS Policy Project
Treatment Action Group