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 (NIH), was chaired by Dr. Gary Nabel, chairman of the AIDS Research Advisory Committee (ARAC). Dr. Killen greeted the committee members and thanked them for their participation. He welcomed Dr. Charles Rinaldo, Jr., as a new ARAC member and mentioned that the NIAID is seeking another individual to fill a remaining ARAC position.
Dr. Killen then addressed budget issues, beginning with a brief review of the FY 1997 funding levels proposed by the President and those approved by Congress. He reported on the overall budget increases from the FY 1996 level for the NIH and NIAID, noting specific increases for NIAID’s non-AIDS and AIDS research.
Addressing scientific developments, Dr. Killen described data from two recently reported studies on the transplacental carcinogenesis of AZT in mice. Data from an ongoing study being conducted by investigators at the National Cancer Institute (NCI) suggest that very high daily doses of AZT may induce tumors in the offspring of pregnant mice given the drug during the last trimester of pregnancy. A transplacental carcinogenic effect of AZT was not seen in a differently designed study carried out by scientists at Glaxo-Wellcome, Inc., (G-W) the drug’s manufacturer. The G-W study attempted to model clinical usage of the drug. On January 14, 1997, NIH convened an independent panel of basic and clinical researchers, epidemiologists, HIV-infected women, and a bioethicist, to review the available data, assist the NIH in developing a scientific summary of the technically complex information, and offer recommendations for future research. The panel concluded that: the known benefits of AZT in preventing perinatal transmission far outweigh the theoretical concerns raised by the NCI mouse study; all HIV-infected pregnant women should be informed of the study results on the transplacental carcinogenesis of AZT in the course of counseling on the potential benefits and risks of treatment interventions; and all children exposed in utero to antiretroviral therapy, including those who are not infected with HIV, should receive careful long-term followup. The panel also outlined basic and clinical research priorities for followup on the carcinogenesis studies. Finally, the panel heard and echoed concerns that the state of the art of antiretroviral therapy has changed (e.g., the use of combination therapies) in the several years since the Public Health Service recommendations on the use of AZT to prevent perinatally acquired HIV infection were developed and suggested a reassessment of the current PHS guidelines. NIAID will broadly disseminate a summary of the available data from the NCI and G-W studies and the independent panel’s recommendations to physicians, professional medical societies, and community organizations.
Dr. Killen also announced the recent appointment of Dr. David Baltimore as chair of the AIDS Vaccine Research Committee (AVRC), which has been established as a coordinating group for the overall NIH vaccine effort in response to AIDS Research Program Evaluation Working Group recommendations (Levine Report). Dr. Carole Heilman, Associate Director for Scientific Program Development for DAIDS and the NIAID point person for AVRC activities, provided an update on planned AVRC meetings and nationwide focus group discussions.
Dr. Killen then asked Dr. Marian Neutra to review the discussion and conclusions from the recent meeting organized by NIAID on mucosal immunology. Dr. Neutra reported that the participants recommended a combined empiric and basic science approach to mucosal vaccine development, with concepts tested in monkeys and humans at the same time as the underlying basic science and mechanisms are elucidated. They also recommended more coordination and direction toward encouraging and organizing the collaboration of investigators involved in mucosal transmission and mucosal vaccine research and suggested supporting more small-scale clinical studies and programs to encourage young investigators to enter the field of mucosal vaccine development.
Report on the External Review of the National Community Advisory Boards/Community Constituency Groups (NCABs/CCGs) - Mr. Martin Delaney
Dr. Killen prefaced the presentation of the report from the NCAB/CCG external review by noting that the review was conducted as part of NIAID’s ongoing commitment to maintaining community involvement in clinical research within the NIAID-supported AIDS clinical research network. NIAID convened the 14-member review panel in August 1996 to evaluate the effectiveness of the NCABs/CCGs associated with the Division’s clinical research and cohort studies.
Mr. Delaney, who served as a member of the panel, reviewed the findings and conclusions of the group.
Overall, the review panel strongly recommended that the NCABs/CCGs continue to be assured access to and provide input on clinical research. The panel agreed that NIAID support of the NCABs/CCGs should be continued as a valuable means of bringing the AIDS constituency into the HIV/AIDS research process. The panel also offered specific suggestions regarding a variety of issues, including training programs for NCAB/CCG members, recruitment and retention of local and national CAB members, and the need for improved communication between NCAB and local CAB members. In response to one of the panel’s recommendation, Ms. Rona Siskind, DAIDS, will coordinate communication across the NCABs/CCGs and will focus on broad issues that affect all of the community groups supported by the Division.
Initiative Development/Scientific Framework: Introduction - Dr. John Y. Killen
Dr. Killen introduced the presentations on the DAIDS scientific framework and proposed initiatives, noting that the goal of this meeting is to provide the joint committees with an opportunity to become involved in initiative development at an earlier stage of the NIAID priority setting process. He stated that the DAIDS scientific framework for initiative development corresponds to the research agenda outlined in the NIAID HIV/AIDS Research Agenda. He encouraged the committee to provide input on emerging topics for new research and identify gaps in the current and planned research portfolios.
Initiative Development/Scientific Framework: HIV Pathogenesis and Epidemiologic Research - Dr. Carl Dieffenbach
Dr. Dieffenbach provided an overview of the NIAID research program in the areas of HIV pathogenesis and epidemiology, noting that the portfolios in these areas are mainly investigator-initiated grants focused on HIV structure/function, host/pathogen interaction, HIV transmission, and disease progression. He emphasized the program priorities of encouraging novel ideas for AIDS research; expanding in vivo research opportunities; stimulating the movement of discoveries in pathogenesis research into vaccines, prevention, and therapeutics; and continuing the cohort studies. He also provided an overview of FY 1998 initiatives and described in broad terms those initiatives being planned for FY 1999 and beyond.
In discussion, committee members affirmed the importance of facilitating funding and evaluation of small grants for novel ideas and on translational research projects. It was noted that more trained scientists are needed in the area of animal models, particularly primate research.
Vaccine and Other Prevention Research and Development - Dr. Pat Fast
Dr. Fast described the NIAID research program in the area of vaccine and other prevention research. She stated that the operational themes of this program area are to: 1) integrate state-of-the-art research with preclinical and clinical studies using standardized evaluations and multidisciplinary collaborations, and 2) adapt to new scientific discoveries with increased administrative flexibility. The scientific themes and directions focus on HIV variation, novel vaccines, mucosal immunity, animal models, and clinical evaluation. She then summarized plans in vaccine and other prevention research for FY 1998 and beyond.
Comments from the committee addressed ensuring effective interaction of the NIAID program staff with the AIDS Vaccine Research Committee and developing mechanisms for quickly implementing recommendations that will advance the field. DAIDS staff mentioned that there are existing resources that would permit a rapid response in most circumstances. Integration of research efforts in the areas of pathogenesis, vaccines, and therapeutics, and issues pertaining to the conduct of vaccine efficacy trials were also discussed.
FY 1998 Initiatives: Concept Review/Discussion
Concept Review: Master Contract(s) for Targeted HIV Vaccine and Related Prevention Intervention Research - Dr. Alan Schultz
Under this initiative, a master contractor(s) will provide scientific management support and the flexibility to solicit qualified subcontractors in a competitive process to perform targeted research. The objective is to enable rapid mobilization of resources in response to pressing scientific needs and opportunities identified as gaps or emerging areas of importance in preclinical and clinical HIV vaccine research or other prevention intervention research. The concept was approved with one modification.
Concept Review: Laboratory Support for AIDS Vaccine and Other Prevention Clinical Trials -Dr. Mary Clare Walker
The objective of this initiative is to establish an additional central support laboratory to expand capacity for standardized high-volume humoral and cellular immunologic and virologic assays on specimens from volunteers in AIDS vaccine clinical trials and other prevention trials. This laboratory will augment the present capacity of existing laboratory contracts (the AVEG and HIVNET Central Laboratories) that support trials at domestic and international sites. The concept was approved.
Concept Review: Variation of HIV-1 and Related Lentiviruses - Dr. James Bradac
Part A: Genetic Variation of HIV-1 and Related Lentiviruses
This initiative proposes continuing funding of activities to study variation of HIV-1 and related lentiviruses to aid in the development of vaccines that are broadly reactive against all strains of the virus. The concept was approved.
Part B: Impact of HIV-1 Variation on Immunological Recognition
This initiative will fund basic research to explore the impact of variation on immune recognition and to provide information that can be utilized in the development of vaccines that are broadly reactive against many strains of HIV that are circulating in the population. The concept was approved.
Concept Review: Primate Immunology Laboratory for AIDS Vaccine Research and Development - Dr. Nancy Miller
The objectives of this initiative are to provide a centralized laboratory for assessment of the immunological responses of primates to HIV and/or SIV vaccines and to obtain comparative immunological data on a variety of vaccines. The contract will continue to support studies conducted at NIAID’s Simian Vaccine Evaluation Units (SVEUs). The concept was approved with two modifications.
Concept Review: AIDS Vaccine Evaluation Group (AVEG) Mucosal Immunology Laboratory - Dr. Mary Clare Walker
This initiative will continue support for the Mucosal Immunology Laboratory (MIL) contract that provides standardized evaluations of mucosal immune responses induced by candidate AIDS vaccines in phase I and II clinical trials conducted by the AVEG. The concept was approved with three modifications.
Initiative Development/Scientific Framework: Therapeutics Research and Development - Dr. William Duncan
Dr. Duncan provided an overview of the NIAID research program in the area of therapeutics research and development, emphasizing the need to promote linkage of basic scientists and clinicians in the therapeutics area. The therapeutics program focuses on primary disease and opportunistic infections (OIs), as well as AIDS-related neurological disease (with the National Institute of Neurological Diseases and Stroke) and malignancies (with the National Cancer Institute). He then presented the major scientific themes in the areas of primary disease, immune reconstitution/immunopathogenesis, and OIs. Dr. Duncan concluded his remarks by describing initiatives that will be implemented in FY 1998. He also discussed proposed plans in therapeutics.
In discussion, comments addressed the need to catalyze research on antiviral therapeutics in Kaposi’s sarcoma, the availability of antibodies for cytokine and chemokine receptors through the AIDS Research and Reference Reagent Program, and possible strategies for conducting small-scale clinical trials.
FY 1998 Initiatives: Concept Review/Discussion
Concept Review: Preclinical Evaluation of Therapies for Treatment of Cryptococcosis - Dr. Chris Lambros
This initiative will continue support for preclinical in vitro testing and animal model efficacy studies of compounds with potential to treat cryptococcal meningitis associated with AIDS. The concept was approved.
Concept Review: Feline Immunodeficiency Virus (FIV) Model of AIDS - Dr. Roger Miller
This Program Announcement is focused on stimulating research on FIV molecular biology with the intent of validating the model for possible use in testing potential therapeutics, topical microbicides, and vaccines. The concept was approved.
Initiative Development/Scientific Framework: Pediatric HIV Disease - Dr. Mary Glen Fowler
Dr. Fowler described NIAID’s portfolio of work directed at pediatric HIV disease, which includes research on perinatal transmission, natural history and pathogenesis, and therapeutics. The goals of this research are to reduce perinatal HIV transmission, cure acute pediatric infection, treat chronic disease in order to promote nonprogression and prolonged survival, and understand mechanisms of transmission and pathogenesis of disease progression. She also described approaches for future perinatal HIV research efforts, future directions in pediatric HIV therapeutics, and outlined initiatives proposed in FY 1999 and beyond.
The committee’s discussion centered on the importance of linking basic researchers to cohort studies; how to advise women regarding the risks of transmission through breast feeding, particularly in developing countries; difficulties in formulating drugs for children; and the status of trials of triple therapy, which has shown promise in infants but needs further study. back to top |