John Y. Killen, M.D., Director, DAIDS
Dr. Killen welcomed everyone to the meeting. He began his report with the news that Dr. Janis Giorgi, a member of the AIDS Subcommittee, died on May 30th after a long bout with cancer. He acknowledged Dr. Giorgi for her outstanding scientific contributions, warmth and dedication. He also thanked Drs. Neutra, Rinaldo, and Dolin, who were completing their terms on the committee, noted several staff changes and provided a budget and programmatic update.
Vaccine and Prevention Research Program Overview - Dr. Johnston
Vaccine Research and Development: Dr. Johnston provided a broad overview of recent advances in pre-clinical and clinical vaccine research and development. Current research and development priorities include strategies to induce more broadly neutralizing antibodies, elicit CTLs in a higher percentage of vaccine recipients, and induce strong mucosal immune responses. DAIDS will continue to support the development of a range of vaccine candidates, and the canarypox prime-boost concept will be pursued toward an efficacy trial. A number of other candidate vaccines are in Phase I trials.
Prevention Research: In one of the most significant advances in the prevention of perinatal transmission of HIV, researchers in Uganda found last year that giving mothers in delivery and their newborn infants a single dose of nevirapine reduced perinatal transmission by about 50 percent. This finding will have a significant impact on activities in developing countries. Other research demonstrated the importance of viral load as an indicator of the likelihood of transmission to a sexual partner, and indicated that circumcision may be a means of reducing HIV transmission. The development of promising microbicides is advancing, and new data are becoming available on how the treatment of STDs effects HIV transmission. Lastly, there is an ongoing trial that will measure the impact of a behavioral intervention among men who have sex with men on HIV acquisition.
Priorities include building on the findings of the nevirapine study (HIVNET 012), especially in determining how to protect children during breastfeeding; identifying and advancing promising microbicides; and improving behavioral interventions in high-risk populations.
Programmatic Priorities: Programmatic priorities for the next 5 years include completing the HIV Vaccine Trials Network and the HIV Prevention Trials Network and ensuring a smooth transition from the existing networks; supporting developmental activities, including ongoing trials, vaccine development, perinatal transmission studies, and the design of comparative phase II studies for microbicides; awarding contracts for the HIV Design and Development Teams; initiating a comparative primate study; maintaining the vaccine research pipeline; and designing a new international program to address gaps in research and infrastructure. The President's vaccine initiative highlights the importance of new approaches to public-private partnerships and the establishment of a global research agenda.
Comprehensive International Program for Research on AIDS - Dr. Rod Hoff
This new 5-year program will provide scientists in developing countries with long-term support for epidemiologic, laboratory, and clinical studies on the prevention and treatment of HIV/AIDS. Grants will be available to countries with limited research capacity as well as those with more substantial research capabilities. The committee approved this initiative with the understanding that NIAID will -
Clarify the logistics of funding domestic and international sites, particularly in instances where the foreign institution is the primary site and the domestic site is a subunit.
Encourage in-country collaboration between local scientific groups, institutions and government.
Include training of foreign investigators and staff to allow them to be competitive.
Clarify intent regarding geographic diversity.
Clarify that the focus is on countries with a high and/or rapidly increasing incidence of HIV infection.
Consider the development of core infrastructure as progress.
HIV Vaccine Production Resources - Dr. Butler
This program will increase support for moving unique, experimental vaccines into primate and human clinical trials. NIAID hopes this program will foster more competitive pricing and increase the number of contractors that can perform key tasks such as preclinical testing for new concepts and FDA submissions.
Committee members acknowledged the need for the program, but questioned the need for additional funding. Although only one project currently needs this type of support, NIAID wants to be able to rapidly respond to and to meet future needs. In order to do so, resources need to be identified now. Contractors will receive a minimal award for being in the pool, but will receive no substantial funding until they actually perform a task. Internal and external oversight groups will be used to help NIAID set priorities. The committee approved the concept.
HIV Vaccine Design and Development Teams - Dr. Dieffenbach
The goal of this project is to increase the number of vaccine modalities and products in clinical trials. Specifically, this concept will support consortia of academic and industrial scientists who have identified promising vaccine concepts, have envisioned products amenable to targeted development, and have significant experience in vaccine development. This initiative is the first NIH program to use performance-based contracts. The first round of this program is almost complete; awards will be announced in summer 2000 and will include diverse prime-boost strategies. The first contractor receiving an award is expected to begin trials within 12 to 15 months and all awardees will enter phase III trials by the end of the third year.
The committee supported this proposal, but wondered if the HVTN, rather than the teams themselves, should directly compare the immune responses of candidate vaccines. Committee members asked about intellectual property and patent rights, and whether the concept could be expanded to include other prevention approaches, including microbicides, and models other than drug-development, biomedical research models. In response, Drs. Johnson and Killen suggested that microbicides be covered by a separate initiative and agreed to explore the program's relevance to other prevention strategies. The committee voted to approve the concept.
New Technologies for HIV and HIV Vaccine-Related Research - Dr. D'Souza
This initiative will fund the development and use of novel technologies to advance HIV vaccine development. Among other projects, this program will foster the development of a wider range of assays that are more sensitive and give more detailed information about immune responses. It will also sponsor research on how vaccines work.
Based on the discussion, the committee voted to approve this concept with the following modifications:
Require investigators to conduct blinded comparisons of the candidate assays with existing assays.
Facilitate efforts to standardize assays through provision of standard reagents where possible. Clarify how applicants will interact with HVTN to access samples.
Include language regarding the need for inexpensive and simple methodologies that could be widely used in developing countries.
Therapeutics Research Program: Concept Review
NIAID sponsored a multidisciplinary workshop in January to explore the issues of when HIV-infected people should start antiretroviral therapy, when and how they should switch therapies, and the long-term efficacy and tolerability of current therapies. Workshop participants saw these issues as the most important non-pediatric research questions that are not currently being addressed. They agreed that these questions would best be investigated through large randomized clinical trials with clinical endpoints at follow-up of up to 10 years. They also thought such studies should be attempted despite their high risk of failure. They agreed that epidemiologic cohort studies could help generate hypotheses and confirm the results of the randomized trials.
When to Start Antiretroviral Therapy - Dr. Duncan
This initiative would support a consortium of sites to study when to start antiretroviral therapy and to assess the long-term outcomes of various therapeutic approaches. It will attempt to determine the optimal timing of initial antiretroviral intervention, evaluate the long-term complications of various strategic approaches, and conduct methodological research needed to answer these questions. Dr. Duncan reviewed the challenges of conducting such a long-term study, including: retention, the ability of physicians to maintain equipoise, and the emergence of changes in the state of the art of treating HIV/AIDS during the course of the study. NIAID plans to evaluate the feasibility of such a study before beginning any specific trial.
The committee voted to approve the concept with the following modifications:
The study design should include a pilot phase to determine feasibility.
Initial decisions to fund and continue funding should be linked to the feasibility and achievement of specific milestones.
Participating sites should have documented experience and ability to ensure long-term follow-up of study subjects (i.e., experience should not be restricted to HIV clinical trials).
The funding plan and concerns of the ARAC regarding feasibility should be explicitly reviewed and discussed by the NIAID Council prior to making grant awards.
When/How to Change Antiretroviral Therapy - Dr. Duncan
The initiative to address the issue of when/how to change antiretroviral therapy would support 1 to 2 multi-center clinical trials designed to address the long-term outcome of various treatment approaches. Specifically, the studies would evaluate viral load and/or immunologic parameters as markers for changing antiretroviral therapies, evaluate long-term clinical outcomes and complications as primary endpoints and conduct relevant methodological research.
The committee voted to approve the concept with the following modifications:
Emphasize that the focus and primary objective of the study is the long-term effect of antiretroviral therapy (ARV) on clinical outcome by reorganizing scientific goals into primary (clinical) and secondary (laboratory) categories.
The study design should include a pilot phase to determine feasibility.
Initial decisions to fund and continue funding should be linked to documentation of feasibility and achievement of other specific milestones.
Participating sites should have documented experience and ability to ensure long-term follow-up of study subjects (i.e., experience should not be restricted to HIV clinical trials).
The funding plan and concerns of the ARAC regarding feasibility should be explicitly reviewed and discussed by the NIAID Council prior to making grant awards.
Acute Infection and Early Disease Research - Dr. Duncan
This 5-year program will continue innovative, investigator-initiated pathogenesis and clinical research on acute and early HIV-1 infection. The program has been underway for more than 3 years. Twenty-five clinical studies involving 500 subjects have been initiated.
Committee members said this program has been productive, although expensive. The committee voted to approve the concept and although there were no formal modifications proposed, it was strongly recommended that the network take better advantage of the research that can be done as a network, collaborate on more multi-center studies, and develop a more active approach for sharing resources among investigators.
Basic Sciences Program: Concept Review
CNovel HIV Therapies: Integrated Preclinical/Clinical Program (IPCP) - Dr. Bridges
This 4-year initiative renews and expands a multidisciplinary program of P01 grants for advancing novel therapeutic concepts into the clinic. This proposal reintroduces the requirement for corporate partnering. A new area of emphasis is the removal of HIV sanctuaries. The committee approved this concept without discussion.
Regulatory Affairs Branch: Concept Review
Regulatory Operations Center - Dr. Luzar
This initiative extends an existing 7-year contract supporting the regulatory work the Division conducts for trials it funds. The committee approved the proposal without discussion.
Office of Program Operations and Scientific Information: Concept Review
DAIDS Research Support Services Project - Ms. Doane
This 5-year contract renewal will provide logistical, technical, and operational support for DAIDS. The committee approved the contract without discussion. back to top |