John Y. Killen, M.D.
Director, DAIDS, NIAID
The meeting, which was held in the Natcher Conference Center on the campus of the National Institutes of Health, was chaired by Dr. Marian R. Neutra, chairperson of the AIDS Research Advisory Committee (ARAC).
Report from the Director -- Dr. John Y. Killen
Dr. Killen welcomed everyone to the meeting, particularly Drs. Nathanson, Carpenter and Phair, who are all new members of the committee. He announced staff changes, welcoming back Dr. Peggy Johnston who will serve as NIAID’s new Assistant Director for HIV/AIDS Vaccines and the Division’s Associate Director of the Vaccine and Prevention Research Program. Dr. Killen also recognized staff members who received NIH Merit Awards and the NIH Director’s Award.
Budget Update. Since NIAID celebrates its 50th anniversary this year, Dr. Killen gave the Committee a brief history of NIAID’s budget, highlighting its 300-percent growth over the last 20 years. Much of this increase has been for AIDS research, which now accounts for 52 percent of the budget.
NIAID has received its House and Senate budget allocations for FY 1999, which include 9- and 14-percent increases, respectively, over the FY 1998 budget. These increases are comparable to the increases granted to NIH overall. Dr. Killen noted several NIH programs that received substantial increases, including AIDS vaccines.
Financial Management Plan. The FY 1999 financial management plan includes a lower payline, set at the 20th percentile for all grants. Programmatic reductions will remain the same, with an average adjustment of 7 percent. The selective pay pool will remain $9M, and the bridge award pool will be increased to $12M.
Dr. Killen highlighted some of the Division’s major scientific accomplishments from the past year. He also outlined the presentations that will be given during NIAID’s 50th Anniversary Symposium by noted scientists. Finally, Dr. Killen noted that DAIDS will be moving closer to the NIH campus.
Programmatic Update -- Dr. John Y. Killen
Dr. Killen updated the Committee on some of the initiatives discussed at the last meeting. He reported that the request for applications (RFA) for the Adult Therapeutics Clinical Trials Program was modified in light of the concerns the Committee raised at the last meeting. Specifically, the Program’s broad agenda will address both technology-intense clinical research and medical management strategy trials, and will support several cooperative groups. The RFA, which was released in July, clearly states the importance of the entire research agenda and provides for submissions from unaffiliated clinical sites and multiple applications from single institutions. DAIDS is working with the Scientific Review Program to ensure that the initial review group has appropriate expertise and balance, and will establish a subcommittee of the ARAC to provide advice on the broad directions of the therapeutics clinical trials program. NIAID held a meeting for potential applicants on September 18.
Dr. Killen then briefed the Committee on the status of the Vaccine and Prevention Trials Networks. The RFAs for these initiatives will reflect the Committee’s previous comments. Specifically, NIAID has developed a two-stage transition plan to ensure a seamless transition from AVEG and HIVNET. In the first stage, separate vaccine and prevention leadership cores will be established approximately 6 months before responsibility for current programs is shifted. The second stage will involve the review and selection of applications from clinical sites. NIAID hopes to make the awards for the leadership cores and clinical site investigators in September 1999 and early 2000, respectively.
Dr. Nathanson, Director of the Office of AIDS Research (OAR), added that OAR has been working closely with DAIDS to ensure that there is funding for these initiatives, especially the behavioral intervention studies. In response to questions, Dr. Killen announced that the RFA for the vaccine program will require a global scientific agenda that coordinates domestic and international research activity. During discussion, Dr. Killen clarified a number of questions, including how solicitations would be issued; how the new leadership cores might influence the selection of the clinical sites; how NIAID expects that the leadership cores and clinical sites might cooperate; how these programs might coordinate with CDC initiatives; NIAID’s priorities with respect to growth in the budget (vaccines, prevention, and pathogenesis research); and how he thinks funding might be structured. Drs. Killen and Nathanson also reaffirmed NIAID’s priority to expand intervention trials. Committee members suggested that coordination between NIH and CDC be more structured and include CDC membership on any steering committees.
Dr. Killen then summarized progress on a number of ongoing program announcements, including the following awards. In cooperation with five other institutes, the Centers for AIDS research grants were awarded to 17 centers for periods of 3- to 5-years. Two new awards were made to expand the Acute Infection and Early HIV Disease Network to seven sites and a new statistical center. Six awards were made to the Integrated Preclinical/Clinical AIDS Vaccine Development Program, covering a range of vaccine concepts. Six Women’s Interagency HIV Study sites were renewed, and a cooperative grant was awarded for the study’s Data Management and Analysis Center.
AIDS Vaccine Research Committee: Update -- Dr. Carole Heilman
Dr. Heilman discussed the recent activity of the AIDS Vaccine Research Committee (AVRC), chaired by Dr. David Baltimore.
Workshops and Scientific Sessions. AVRC has hosted a series of regional workshops across the U.S. and one in Europe to bring together investigators who are not necessarily involved in AIDS vaccine research in order to share a variety of important perspectives. Each vaccine committee meeting has focused on a particular scientific area, such as live attenuated vaccines, neutralization, and nonhuman primates. Dr. Heilman summarized the recommendations from these meetings.
Innovation Grants. AVRC has helped fill the "research pipeline" by leading the Innovation Grants initiative. AVRC has been so pleased with these grants that they will be expanded to cover a wider variety of innovative ideas. Current areas of emphasis include animal models, viral-host interactions, vectors, T cell health, and T cell memory.
Future Focus. AVRC’s top priorities has been to fill the vaccine pipeline and to date, it has focused heavily on evaluating the work supported by DAIDS. AVRC will now begin to look at the rest of NIH’s vaccine research program, translational needs, and clinical trials. An NIH/AVRC meeting will be held in May 1999 to review progress and needs in key areas of vaccine research and development.
Dr. Heilman responded to committee members’ questions on topics including what NIAID is doing to encourage grantees to compete for RO1 grants, what bridging strategies are being developed, and who the new vaccine investigators are.
Office of AIDS Research: Vision for the Future -- Dr. Neal Nathanson
Dr. Nathanson stressed that OAR is working to define a role for itself that is complementary to NIAID’s. Half of the overall NIH AIDS budget goes to NIAID’s research, and the other half goes to other Institutes.
Dr. Nathanson noted that OAR published its vision statement in Nature in August. Since HIV is exploding internationally from a public health point of view, OAR will focus on intervention research at points where disease, death, or new infections can be prevented. This initiative will include products such as vaccines and microbicides, and also focus on population- and site-specific behavioral interventions. Dr. Nathanson summarized how OAR supports NIAID initiatives through budgeting and consulting on priorities. During discussion, he emphasized the importance of converting innovative ideas into products that can be used in Phase I trials. OAR is supporting this effort by helping to find more sites where necessary product research can be done. Finally, Dr. Nathanson presented OAR’s response to criticism that NIH is spending too much on AIDS research.
During the discussion, Committee members stressed the importance of focusing on intervention studies, including those dealing with biomedical issues, on particular populations, including minorities and adolescents. They also asked that more grants be awarded to minority scientists. Dr. Nathanson confirmed that OAR is interested in seeing more intervention studies directed to sites and populations where the epidemic is concentrated. He agreed that more minority researchers are needed and said that OAR monitors the demographic profile of the subjects participating in NIH-supported trials.
Concept Review: HIV Sequence Database and Analysis -- Dr. Jim Bradac
Dr. Bradac asked the Committee to approve a concept for the 7-year renewal for the HIV Database and Analysis Unit initiative, which has been in place for about 12 years.
The committee voted to approve this concept and suggested that attention be given to making the database more "user friendly" and efficient. In particular, the committee suggested developing a mechanism for consumer feedback.
Concept Review: Laboratory Methods to Measure Vaccine Responses -- Dr. J. Flores
Dr. Flores presented a new proposal for developing and improving technologies for assessing immune responses to HIV vaccines. This work would include the improvement of existing functional assays and the expansion of the breadth of functional assays available.
Reviewers’ Reports. Dr. Ellner strongly endorsed this concept, emphasizing how much it is needed since the surrogates commonly used are not validated and have great technical variability. He suggested that the work be done with access to clinical populations, possibly in conjunction with clinical trials or in collaboration with other programs.
In discussion, committee members mentioned the importance of early interactions between potential grantees and the clinical trials networks to secure the availability of specimens. The need for coordination with the Therapeutics Research Program, given that the assays will also be used to evaluate immune responses in infected individuals was also discussed. The committee voted to approve this concept.
Concept Review: HIV Therapeutics: Targeting Research Gaps -- Dr. N. Sarver
Dr. Sarver presented a program that would attempt to fill specific research gaps within HIV therapeutics. Specifically, the program would fund research proposed by investigators to validate new therapeutic targets, maximize the potential of currently used drugs, and validate innate immune responses for therapeutic application.
The Committee discussed whether this program would overlap substantially with industry efforts in this area. Several members and staff indicated that industry is not doing enough at the earliest stages of discovery of novel approaches and expressed their concern that the pipeline is too thin. Dr. Killen said NIAID sees this program as creating opportunities for industry to exploit. In response to the concern that the proposal excludes additional work on protease inhibitors and reverse transcriptase, Dr. Sarver clarified that all novel approaches to existing targets are eligible.
The committee voted to approve this concept with three modifications: 1) emphasize novel and immunological approaches; 2) ensure regular communication with industry to avoid duplication; and 3) ensure a mechanism for obtaining broad and informed input on, and implementing changing scientific priorities.
Concept Review: Preclinical Therapeutics Development Resources -- Drs. Kagan and Sarver
This concept involved a package of preclinical therapeutics discovery and development resources to help investigators discover and develop new HIV therapeutics.
In Vitro and Animal Model Testing Resources for Therapeutics Development -- Dr. Sarver
Dr. Sarver presented four recompeting initiatives for in vitro virology testing on HIV therapeutics and topical microbicides, in vitro immunology testing on immune-based therapeutics entities, and in vivo testing on HIV therapeutics.
In response to the Committee’s concern about the SCID mouse model, Dr. Sarver emphasized that NIAID has been very strict about what compounds move into this testing. She acknowledged that the model is limited, but noted that it has been validated and that it has moved several compounds forward. She also noted that there is no ideal model for HIV infection, but that changes could and would be instituted if the state of the science changes.
The Committee voted to approve this package of concepts for these 3 initiatives, suggesting that a better small animal model should be used if one becomes available.
Chemistry and Pharmaceutical Resources for Therapeutics Development -- Dr. Kagan
Dr. Kagan presented the more traditional drug development resources NIAID has maintained. He emphasized that NIAID would like to keep the elements of this package together.
The committee voted to approve the concept for this package of 4 initiatives. back to top |