Ed Tramont, M.D., Director, DAIDS
The AIDS Subcommittee of the National Advisory Allergy and Infectious Diseases Council and the AIDS Research Advisory Committee (ARAC) met jointly on January 17, 2002, at the Natcher Building on the National Institutes of Health (NIH) campus in Bethesda, MD. Drs. Edmund Tramont and John Phair chaired the meeting.
Report from the Director-Dr. Tramont
Dr. Tramont presented a new mission statement for the Division of AIDS (DAIDS), which emphasizes the importance of HIV therapeutic and prevention research in developing countries. He called for the establishment of a working group to review DAIDS' entire research agenda in light of the Division's expanding priorities and need for research in support of the Nation's defense against bioterrorism.
The integration of the Division's prevention and therapeutics research in developing countries will place unprecedented demands on the budget and will intensify the need for training, strong international collaboration, and research infrastructure in the developing world. To meet these goals, the Division is establishing new grants for infrastructure development in the developing world and is coordinating scientific objectives and operations, integrating the study of infectious diseases, and establishing a core database linking NIAID's international research efforts.
Dr. Tramont also announced that NIAID is collaborating with Merck & Co. to test their HIV vaccine products. He also reviewed the new, more streamlined format for concept review, with program directors taking a larger role, summarizing reviewers' comments, and then presenting NIAID's response.
Program Overview and Concept Review
Basic Sciences Program-Dr. Dieffenbach The Basic Science Program facilitates research on HIV, applies the information gained to prevention and therapeutic strategies, and expedites the speedy development of vaccines and therapeutics. The Program's Pathogenesis and Basic Research Branch is focusing on determining the mechanisms of viral entry and binding, and the establishment of infection; the factors affecting pathogenesis and the progression of HIV disease; and the evolution of lentivirus. The Epidemiology Branch is investigating the long-term, natural history of antiretroviral (ART)-treated disease; determining the host genetic viral factors and cofactors affecting survival; identifying gender and ethnic differences in viral load and response to therapy; and determining how ART affects HIV transmission. Finally, the Targeted Interventions Branch is examining potential candidates for microbicide development; identifying new viral and host targets; and eliminating obstacles to proof-of-concept testing of gene therapies. The Branch is also determining whether innate immunity can be manipulated to prevent or treat HIV infection, whether therapeutic vaccines might be beneficial, and whether viral reservoirs can be targeted and eliminated. Dr. Dieffenbach presented one concept for the Committee's approval.
HIV Therapeutic Gaps:
This 3-year initiative would continue to target research gaps in preclinical therapeutics, from basic research through clinical trials. The program funds investigator-initiated proposals and will cost $3M in its first year. If renewed, it will focus on eliminating HIV reservoirs and reconstituting immunity. The Committee approved the concept.
Vaccine & Prevention Research Program-Dr. Johnston
Dr. Johnston briefed the Committee on the current state of vaccine and other prevention research. Advances that occurred in 2001 include the development of new envelope vaccine candidates and potential targets for vaccine development, and progress with canarypox candidates. The preclinical vaccine pipeline expanded, and some candidate vaccines succeeded in controlling disease in primates. In prevention research, the benefits of nevirapine were sustained for 18 months postpartum; new data indicated that circumcision offers protection against transmission to women; and promising microbicide candidates were found to be suitable for further testing.
Key scientific challenges for 2002 with respect to vaccines include development of vaccines that elicit broadly neutralizing antibodies and broader cellular responses; identifying correlates of immune protection, exploring the effects of viral latency on vaccine efficacy, and conducting human trials with promising vaccines. With respect to microbicides, challenges include identifying the mechanisms of entry, determining how and when infection is established, designing safe agents that block infection, combining agents that act at different stages of viral replication, finding a proof of concept for microbicides in humans, and conducting human trials. Other priorities include reducing the transmission of HIV during breastfeeding and developing the ability to conduct research in developing countries. Dr. Johnston warned that controversy over human trials is inevitable and will arise regardless of whether trials begin sooner, from those who think testing is premature, or later, from those who think it is taking too long to begin. Dr. Johnston presented four concepts related to vaccine and other prevention research.
HLA Typing and Epitope Mapping Relative to HIV Vaccine Design
The concept for this 5-year initiative will enable researchers to acquire more information about HLA and T cell epitopes, particularly in regions where trials are anticipated. First year costs are $4M. The contractor will establish HLA types and allelic frequencies, identify T cell epitopes and frequencies, sequence HIV variants, compile datasets, and disseminate this data to the scientific community. Both infected and uninfected individuals will be surveyed.
HIV Vaccine Design and Development Teams
The renewal of this initiative will help researchers take promising vaccine concepts into trials. First-year costs will be approximately $15M. Awards would be for 5 years, with researchers being paid only after specified milestones are met.
HIV Vaccine and Microbicide Preclinical Development
This 5-year initiative will help NIAID identify promising vaccine and microbicide candidates and rapidly bring them into clinical trials. First year costs are $5M. The initiative will support a master contractor who would provide information management and would award subcontracts for vaccine and microbicide production, the goal of which is to expedite vaccine and microbicide development. The contractor would be required to have core personnel near NIAID's offices. The infrastructure developed via this initiative could also support bioterrorism research.
HIV Clinical Research Management Support
This 5-year initiative will provide flexible clinical research management support associated with the planning, implementation and conduct of HIV clinical trails, primarily in international settings. This could include providing staff at international clinical research sites (including Africa, India, Eastern Europe and Asia), general and trial-specific operational assistance, advice on regulatory requirements and international requirements for country-specific approvals, site monitoring, and logistical support for meetings, material distribution and communications. First years costs are $23M and could cover either a large trial or a set of small trials. The contractor must have experience in international settings and be able to provide key personnel near NIAID's offices.
The committee approved all four concepts.
Therapeutics Research Program-Dr. Duncan
Dr. Duncan reviewed the status of the HIV/AIDS epidemic in industrialized nations and the developing world. He summarized the Program's scientific priorities, including developing new targets and drugs to minimize viral replication and tissue burden; evaluating and optimizing strategies for treating special populations including pregnant women, adolescents, children, and those in the developing world; enhancing the HIV-specific immune response; preventing and treating complications related to ARV; and evaluating strategies for treating co-infections. Dr. Duncan reviewed NIAID's contracts for streamlining the development of HIV/AIDS therapeutics and discussed key studies and collaborations related to the optimization of ARV therapy. Dr. Duncan proposed three concepts.
Complications of Antiretroviral Therapy
This 3-year initiative will fund investigator-initiated grants to examine the mechanisms of metabolic disturbances associated with highly active antiretroviral therapy. The initiative will be co-sponsored with the National Institute of Diabetes and Digestive and Kidney Diseases and will cost $1.5M in the first year.
National Cooperative Drug Discovery Group
This initiative renews support for private and commercial efforts to develop new therapies for tuberculosis (TB). It is a 5-year initiative and has a budget of $1.5M in the first year.
Joint Initiative on TB Animal Models
The initiative would provide capacity for evaluating TB drug candidates. This is a 7-year program with a budget of $1M in the first year. It will provide rapid screening for antibacterial activity, bioavailability, and toxicity; assess pharmacokinetics for dose, schedule, and route of administration; and expand the current capacity for testing. This concept is flexible with respect to rapid screening systems and emphasizes the investigation of persisting organisms.
The Committee approved all three concepts.
Discussion
Dr. Phair asked for the Committee's reaction to the new meeting format and the earlier teleconferences among reviewers and staff. Committee members liked the new format, and appreciated seeing how concepts for initiatives were revised in response to their comments. They also appreciated the efficiency and having the meeting compressed into one day. Members also found value in the teleconferences, which permit more in-depth discussions with staff and allow the Committee to review concepts more thoroughly. Some Committee members requested the option to participate in these conference calls, even when they are not designated reviewers.
Committee members also noted, however, that the new format limits their role at the meeting and does not provide enough interaction. Some asked NIAID to clarify their role and suggest how they might be more helpful. They suggested that a Committee member, as opposed to staff, summarize the reviewers' comments. They also asked for a means by which they might contribute more meaningfully to the Division's overall strategic planning even before concepts are drafted. In addition, they suggested that extra time at meetings be used for an in-depth discussion of one overarching issue at each meeting.
Dr. Tramont concurred that Committee members should summarize reviewers' comments at the meeting, and agreed to open the teleconferences to all Committee members who wish to participate. It was also suggested that reviewers' comments be posted on a secure Web site, so those who are unavailable for teleconferences can still participate in the reviews. Staff urged Committee members to contact them at any time with their suggestions. Dr. Tramont asked Committee members to submit a list of issues they would like to discuss at meetings and he will assess the Committee's priorities and schedule issues for discussion.
Dr. Tramont informed the Committee that he would like ARAC to have a larger role in strategic planning. To that end, he is forming a working group to review DAIDS' entire research portfolio in view of the Division's goals for the next 5 years. This working group will be comprised of eight scientists who are not grantees and have the time to devote to this effort; their input will assist OAR as well as DAIDS. Mr. Martin Delaney, and Drs. Gordon Douglas, Ed Kilbourne, John Phair, Phil Russell, and Cathy Wilfert have agreed to participate. ARAC members are also welcome to participate. When completed, the Working Group's report and recommendations will be presented to this Committee. back to top |