March 13, 1996 - Final
Fifteen years of AIDS research have begun to yield new dramatic interventions
that can prevent disease, prolong health, improve quality of life and extend
survival. With the development of new, more powerful, anti-HIV drugs, we have
the first real chance to transform HIV disease from an inexorably fatal condition
to a chronic, manageable viral infection, and in the case of children born
to HIV-infected women, actually prevent many HIV infections. Great strides
have been made in understanding basic aspects of the biology of HIV, and these
insights lay a strong foundation for the development of even more effective
therapies to treat HIV infection and new intervention strategies to prevent
infection.
The present challenge for the biomedical research community is to use our
newly acquired knowledge expeditiously to develop new and better therapies,
to derive effective vaccines and behavioral interventions, enabling us to stop
the expanding devastation of AIDS, and to one day eradicate the disease entirely.
To guide the National Institutes of Health (NIH) in these new directions, a
unique process was undertaken. A group of scientific experts from outside the
government was assembled and asked to evaluate each of the components of the
current NIH AIDS research program. This review was unprecedented in its breadth
and scope, due to the magnitude of the research program, which cuts across
every NIH institute and center. The group was asked to take a broad view in
assessing how these components fit together and determining whether the program
as a whole is moving effectively and efficiently toward the goal of preventing
and curing AIDS.
The United States funds 85 percent of the worldwide public sector investment
in AIDS research. The driving force of this research effort is the NIH, whose
portfolio of AIDS and AIDS-related research has grown from a several-million
dollar investment during the early 1980s to a $1.4 billion effort today involving
virtually all of the Institutes and Centers.
This report provides a blueprint for restructuring the NIH AIDS research
program to streamline research, strengthen high-quality programs, eliminate
inadequate programs, and ensure that the American people reap the full benefits
of their substantial investment in AIDS research.
In late 1994, the Office of AIDS Research (OAR) Advisory Council, chaired
by Dr. Charles Carpenter of Brown University, established the AIDS Research
Program Evaluation Working Group. Dr. Arnold Levine of Princeton University
was recruited to lead this group of outstanding scientists and community advocates.
The Working Group subsequently established six Area Review Panels to review
AIDS research on Etiology and Pathogenesis; Drug Discovery; Clinical Trials;
Vaccine Research and Development; Behavioral, Social Sciences and Prevention
Research; and Natural History, Epidemiology, and Prevention Research. Over
100 scientists from academia and industry as well as community advocates participated
in these panels.
The six panels and the Working Group met regularly throughout 1995 and early
1996 to review information provided by the NIH Institutes, Centers and Divisions
(ICDs) that conduct and support AIDS research and to review budget and program
information retrieved from databases maintained by the OAR and the Division
of Research Grants (DRG). In addition, reviewers met with ICD Directors, key
program staff, intramural and extramural scientists, and a wide variety of
experts from inside and outside the field of AIDS research. Special ad hoc subpanels
were convened to examine cross-cutting issues, such as animal models, opportunistic
infections (OIs), AIDS centers, complementary and alternative medicine treatments,
methods to increase the number of AIDS researchers, and the optimization of
community involvement in the NIH AIDS research program.
Each Area Review Panel identified the scientific priorities within its area,
evaluated the current research portfolio, and developed recommendations to
improve, enhance, and streamline AIDS research. The individual Area Review
Panel reports document their specific evaluations and detailed recommendations.
The Working Group took a broader view, identifying key issues and developing
major recommendations that span scientific areas and underpin the overall NIH
AIDS effort. In some cases, the Working Group report reflects a consensus position
that reconciles somewhat divergent conclusions found in individual Area Review
Panel reports.
Recitations of the numbers of cases of AIDS and HIV infection cannot possibly
convey the magnitude of human suffering experienced by millions of infected
individuals and their loved ones around the world. The HIV/AIDS pandemic holds
the potential to become one of the most costly and debilitating scourges of
humankind. AIDS kills people in their most productive years. In the United
States and other countries, AIDS is the leading cause of death among young
people.
The World Health Organization estimates that, worldwide, nearly 20 million
men, women, and children already have become HIV-infected; 4.5 million of these
individuals have progressed to AIDS; and 2.5 million have died. Nearly 10,000
new infections occur each day. Over 5 million children under 10 years of age
will be orphaned as a result of the death of their parents from AIDS. The increasing
magnitude of the AIDS pandemic will result in unprecedented levels of personal
suffering, high direct costs of medical care for infected persons, reduced
economic output in many countries struggling for economic growth, and other
substantial costs to society.
In the United States, the demographics of the epidemic are changing, increasingly
resulting from heterosexual transmission, affecting greater numbers of women,
and disproportionately affecting persons from racial and ethnic minorities.
The signal successes of AIDS research, many of them made possible by NIH
support, include the following:
In response to the emergence of the HIV/AIDS epidemic in the early 1980s,
the NIH received a major infusion of funds appropriated by Congress earmarked
for AIDS research. Most of the earliest AIDS research was conducted by the
National Cancer Institute (NCI) and the National Institute of Allergy and Infectious
Diseases (NIAID), which by 1985 was the lead institute sponsoring AIDS research.
The challenges posed by AIDS, however, exceeded the mission of any individual
institute. AIDS is a multi-system and multi-organ disease, involving malignancies,
opportunistic infections, neurological, gynecological, ocular, oral, dermatological,
and gastrointestinal complications. It affects people across the life span
from infancy to old age. Behavioral and biomedical interventions are required
to prevent new infections. Consequently, virtually every ICD became involved
in conducting or supporting AIDS research.
This burgeoning effort required coordination. The OAR was established in
1988 for this purpose. However, its limited authority hindered its ability
to fully coordinate the diverse AIDS-related research carried out by the ICDs.
In turn, this limited the ability of NIH to set overall scientific priorities,
manage the vast research endeavor, and evaluate and assess progress against
the disease.
One solution to coordinate this diverse research might have been to establish
a new institute dedicated to AIDS research. However, such an action would have
involved considerable disruption of ongoing science. It became clear to many
concerned scientists, legislators, and community representatives that greater
authority was needed to strengthen the OAR so that it would function as an "institute
without walls." Congress subsequently passed the NIH Revitalization Act
of 1993, which significantly strengthened the OAR, providing it with the authority
to plan, coordinate, and evaluate AIDS research, to set scientific priorities,
and to determine the budgets for all ICD AIDS research. The Working Group and
Area Review Panels unanimously recognize and endorse the crucial need for a
continued strong and viable OAR to provide the overall scientific leadership
and coordination of the NIH AIDS research program.
While much of the NIH AIDS research portfolio is of the highest quality and relevance, the Area Review Panels and the Working Group were convinced that there is a need for improved focus and better coordination between ICD research programs. Many specific needs and recommendations were identified in the individual panel reports; however, a number of common themes emerged:
Because the OAR has the authority to plan and coordinate NIH AIDS research,
the Working Group charges the OAR to rapidly develop and implement an action
plan to address the specific needs identified by this evaluation. We also call
on the NIH Director, the OAR Director, and the ICD Directors to work with the
research community in a collaborative spirit to expedite the implementation
of the proposed recommendations.
The nurturing of novel research approaches, concepts, and directions is essential
for progress against AIDS. Research innovation and productivity require adequate
levels of funding for meritorious projects, stability of grant support for
productive, experienced AIDS researchers and an ongoing infusion of new investigators
to the AIDS field. The Working Group believes that the success of the NIH's
AIDS research effort absolutely depends on high-quality, informed peer review
of research proposals.
The Working Group believes that there is no better way to enhance the diversity and productivity of research approaches than to actively encourage and support peer-reviewed, investigator-initiated and driven research. This principle holds true for all areas of AIDS research including the basic sciences, the clinical sciences, the epidemiological sciences, and the behavioral sciences. However, the pool of funds dedicated to support investigator-initiated AIDS research is proportionally less than those typically devoted to other NIH-sponsored research programs. Indeed, in 1994 only about
20 percent of NIH AIDS extramural research expenditures could be classified
as unsolicited investigator-initiated research, as compared with approximately
50 percent for nonAIDS projects. Since the beginning of the AIDS epidemic,
the ICDs have tended to manage AIDS research with more direct scientific control
than other research portfolios. Requests for applications (RFAs), collaborative
agreements, and contracts were heavily utilized as research support mechanisms.
Earlier in the epidemic, when the available level of knowledge was less and
the community of researchers involved in AIDS research was smaller, this was
an effective approach to establish the infrastructure and preliminary knowledge
base for nascent AIDS research efforts. However, given the maturation of the
field and the nature of the contemporary research needs, the continuation of
this approach represents an impediment to progress.
A primary consequence of the current distribution of funds is that the resources
available for unsolicited investigator-initiated research are simply insufficient.
Proposals that ultimately receive funding most often do so only after multiple
submissions for review. Delays resulting from multiple review cycles inevitably
slow progress that can be made against the disease. Another negative consequence
of the intense competition for research dollars is that many investigators
are reluctant to submit novel or innovative proposals. Furthermore, the tight
competition for grants has led IRGs to heavily favor applications containing
extensive preliminary data. While this is an important criterion by which to
evaluate the merit of grant applications, it represents a major barrier to
attracting new investigators to the field of AIDS research.
To remedy this situation, the Working Group recommends a substantial increase
in the support for investigator-initiated AIDS research across the NIH.
The Working Group is aware that this increase may result in different paylines
for AIDS and non-AIDS research. The Working Group has determined that there
are funds allocated for AIDS research that are being used to support both intramural
and extramural research that is only peripherally related to AIDS. Redirection
of such funds will be required to implement this recommendation. The Working
Group appreciates that such redirection of funds will require time and careful
planning.
The OAR is responsible for the development of an annual plan for NIH-sponsored
AIDS research that sets scientific priorities. The development of this plan,
which involves input from ICDs and from a wide range of extramural scientists,
is an essential function. Similarly, the independent peer review mechanism
used to judge scientific accomplishments and novel ideas is the most effective
means to support high quality research. However, there are, at present, no
effective means to link the AIDS research priorities identified by the NIH
Plan for HIV-Related Research to the consideration of competing research grant
proposals by the peer review groups. The Initial Review Groups (IRGs) and the
Division of Research Grants (DRG) should be better informed of the scientific
priorities for AIDS research and should consider these priorities in their
review of grant proposals for AIDS and AIDS-related research. To accomplish
this goal, the Working Group recommends that:
Although improved linkages between AIDS research priorities and IRG review
is needed now, it will become increasingly important in the future, particularly
as increases in funding for investigator-initiated research are realized. It
must be emphasized that this recommendation is not an attempt to interfere
with the independent judgment of scientists or of IRGs. Rather, it is meant
to encourage better coordination of scientific goals.
The peer review process is central to the success of the entire research
endeavor. It must be of the highest quality. The paramount consideration in
achieving expert peer review is the scientific expertise of the members of
the IRGs. Scientific expertise can be defined through previous record of scientific
accomplishment and knowledge of the field relevant to the review. The Working
Group became aware of numerous instances where the IRG process unfortunately
appears to have failed in the identification of the most promising research
projects. The Working Group believes that these failures were primarily due
to limitations in the breadth, depth, or expertise of the membership of certain
AIDS-related IRGs. These limitations seem to be the result of a number of factors,
including constraints placed on DRG with respect to choosing IRG members, the
limited enthusiasm that many members of the extramural scientific community
may feel for service on IRGs in an environment where so few grant applications
are funded, and the absence of an aggressive campaign on the part of the NIH
and DRG to recruit expert scientists to serve on IRGs. The Working Group strongly
believes that these limitations must be remedied.
AIDS research is continually evolving, so that areas of scientific emphasis
will inevitably change over the next 5 years. There likely will be increased
opportunities and needs in the future for basic, clinical, epidemiological,
and behavioral scientists to collaborate in multidisciplinary studies. To expertly
evaluate these multidisciplinary approaches and their translational research
opportunities, it will be essential that IRGs include appropriate expertise
in basic, clinical, and behavioral research. DRG should select members of IRGs
and review panels with broad scientific scope and expertise to ensure that
meritorious new directions and ideas are approved for funding. To support and
maintain the highest quality of AIDS research and to identify promising new
research directions, the Working Group recommends that:
I.8 DRG should be responsive to the evolving character of AIDS research
and modify IRG composition or define new IRGs as needed. The Working Group
believes that the existing AIDS-related IRGs should be redefined and reconfigured
to reflect the current scientific priorities for AIDS research, particularly
as they relate to vaccine and prevention science research needs.
It is critical that the NIH actively encourage exceptionally creative and
productive individuals to devote at least a portion of their research effort
to HIV/AIDS-related areas. A number of factors may have contributed to limited
success in attracting many expert investigators to AIDS research in the past.
These factors include concerns about working with infectious agents, unfamiliarity
with the central scientific issues in AIDS, the perception that the field was
insufficiently mature to support very focused investigations, the daunting
complexity of the disease process, a lack of understanding of the human immune
system and of tools to study it in detail, and the often public and contentious
nature of the earlier AIDS research effort. Many of the barriers have lessened
significantly over the past decade. Although provision of adequate funding
to investigator-initiated research is, as discussed earlier, a necessary component
of a program to attract new investigators to AIDS research, it is not the only
remedy that is needed. The NIH must ensure that the remaining obstacles are
addressed as well.
In the current NIH funding environment, it is very difficult for researchers
who are just beginning their independent scientific careers to compete against
more established investigators for funding. As the financial constraints on
universities and academic medical centers continue to mount, new investigators
are under increasing pressure to rapidly gain independent support. Delays in
obtaining research support or the inability of attracting sufficient levels
of funding to establish an independent research program can result in either
the loss of a junior investigator's position or redirection of his or her efforts
to teaching, service or clinical responsibilities.
The NIH has been successful in recruiting investigators to understudied areas
of science in some instances. The Working Group identified several features
that are likely to be important to achieve such success in the area of AIDS
research. Key among them are the quality and dedication of NIH staff involved
in program initiation and oversight, and the involvement of the extramural
scientific community in identifying research needs and opportunities. The Working
Group recommends an active program to recruit outstanding new investigators
to AIDS research.
The development of a safe and effective vaccine to prevent HIV infection
is among the highest priorities for the AIDS research effort. Yet, vaccine
research historically has received less funding and attention than other areas
of AIDS research. Although this may have been justifiable in the past, the
continued spread of the HIV epidemic and recent advances in our knowledge dictate
a reassessment of priorities and a restructuring of the NIH vaccine initiative.
In many developing nations, vaccines may be the only cost-effective way to
prevent transmission and control the pathological consequences of HIV infection.
Despite the urgent need, efforts to develop an HIV vaccine candidate that is
likely to be highly effective have been unsuccessful to date. These efforts
have been impeded by the lack of a good animal model for HIV challenge studies
and our failure to identify specific correlates of immune protection, as well
as other factors. However, dissection of immune responses from animals protected
by vaccination or studies of individual humans who appear able to control HIV
replication and possibly resist infection may provide new insights for vaccine
development. While the course and time to an effective AIDS vaccine cannot
be predicted, there can be no question of the importance of the effort.
The Working Group and the Vaccine Area Review Panel concluded that only with
reinforced effort and commitment will a vaccine against HIV-1 be attainable.
Successful development of an effective vaccine to prevent HIV-1 infection will
require major investments in fundamental human immunology and vaccine biology
to derive new and more potent vaccine approaches. Strategies also are needed
to identify and prepare promising candidate vaccines for clinical trials, and
to rapidly move them, when warranted, into full-scale efficacy trials.
The Working Group recommends the creation of a restructured, trans-NIH vaccine
program with centralized leadership to mobilize and focus the necessary resources
to expeditiously pursue these objectives. Critical to the success of this initiative
is its organization and leadership structure. The Working Group also believes
that the NIH has an indispensable role in coordinating this vaccine effort
with those of other government agencies, of industry, and of international
organizations.
An AIDS Vaccine Research Committee (AVRC), chaired by a distinguished non-government
scientist, should be created to provide leadership, direction, and oversight
to a comprehensive AIDS vaccine effort, spanning all ICDs. This effort should
be established as an independent Center or Division administratively located
in NIAID. Day-to-day operations of the unit should be the responsibility of
a scientific and administrative expert. The composition of the AVRC should
include a majority of members who are outstanding non-government scientists
with appropriate expertise; representatives of ICDs with major vaccine programs;
and a representative of the OAR. Members of the AVRC should be jointly appointed
by the Director of NIH, the Director of OAR, and Director of NIAID.
Coordinated direction across ICDs and between intramural and extramural investigators
is necessary to achieve effective planning and implementation of strategies
to rapidly exploit new advances. In addition to facilitating the development
and evaluation of HIV vaccines, this initiative should stimulate the integration
of basic research advances in immunology and vaccine science that could energize
the development of new vaccines for a wide range of infectious diseases, including
microorganisms that cause opportunistic infections.
This Task Force would integrate government-sponsored vaccine research and
development efforts of all U.S. government agencies and coordinate them with
those of pharmaceutical and biotechnology organizations, private agencies,
other nations, and international organizations.
HIVNET was established in 1993 as a network of domestic and international
sites to primarily support trials of promising AIDS vaccine candidates but
also to test non-vaccine biomedical and behavioral interventions. The most
important accomplishment of HIVNET to date is its success in recruiting large
numbers of individuals at high risk for HIV transmission into cohorts for baseline
studies. The program is gathering data on risk and incidence of HIV infection
and willingness to participate in future vaccine trials, as well as evaluating
consent procedures. In the absence of testable vaccine candidates, the current
agenda for the HIVNET program involves continuing baseline measurements and
implementing non-vaccine studies that include other prevention interventions-both
biomedical and behavioral-that will be important adjuncts to the vaccine initiative.
The Working Group acknowledges the potential value of the seronegative cohorts that have been established in HIVNET for identifying newly infected individuals and for testing biomedical and behavioral interventions designed for prevention of HIV transmission. However, efforts to integrate behavioral interventions within the existing HIVNET program have not yet been fully successful. Such efforts have been impeded both by a lack of appropriate expertise in behavioral and social science research and by the Master Contract mechanism, which limits the access of potential subcontractors who have such expertise. The Working Group found that, because the principal mission of HIVNET has been vaccine preparedness, it is not obvious that it has the intrinsic expertise or infrastructure to move effectively beyond this mission on a broad scale. Moreover, with a potential vaccine candidate currently being evaluated within the AIDS Vaccine Evaluation Group (AVEG) for possible efficacy studies beginning in 1998, it is not clear how existing studies of non-vaccine interventions would be affected if a vaccine candidate were available for trial, or alternatively, how these intervention studies will impact potential vaccine trials. Finally, it can be argued that the Master Contract mechanism may not be optimally conducive to an effective leadership structure within HIVNET, or to the ability of NIAID to manage this program.
Because of the significant amount of resources committed to this effort and
the complexity of the scientific issues to be addressed, the Working Group
believes that a comprehensive plan for HIVNET's activities must be developed.
Strong scientific input from other ICDs is needed, particularly in the areas
of behavioral and biomedical prevention studies. Furthermore, because HIVNET
is a broader prevention research program, it should not be categorized, budgeted,
or evaluated as strictly a vaccine development initiative.
There is a critical need for a greater understanding of the human immune
system. Illumination of the intricacies of this system holds the keys to developing
a successful vaccine to prevent HIV infection and for designing more effective
therapies to limit immune system damage and to restore functional immune responses
in HIV-infected persons. Great progress has been made in immunology research
over the past few decades, yielding fundamental insights into the pathogenesis
of infectious diseases, autoimmune diseases and cancer. Progress has been built,
in many instances, on a foundation of basic knowledge derived from the study
of the mouse immune system. Study of the mouse immune system has been greatly
facilitated by the availability of strains of inbred, transgenic and 'gene-knockout'
mice. Insight into the function of the immune systems of humans and non-human
primates has progressed more slowly, largely due to their greater complexity
and less experimentally-tractable nature. Unfortunately, simple translation
of results from the mouse immune system to immune systems of primates may prove
to be very misleading. The study of HIV/SIV immunology in human and primate
models is under represented in the scientific portfolio of the NIH. Many of
the most capable immunologists have not committed major efforts to AIDS research.
Research on the immune systems of uninfected, and HIV-infected humans and SIV-infected
primates must be established as a high priority for the NIH. To focus attention
on HIV/SIV immunology and actively engage talented immunologists in AIDS research,
the Working Group recommends:
As the AIDS epidemic continues to spread into new communities in the United States and globally, primary prevention of new HIV infections must be a high priority. As of FY 1994, only about
6.5 percent of the total NIH AIDS research budget was devoted to non-vaccine
primary prevention-intervention research.
A major goal for NIH should be to develop an HIV Prevention Science Agenda
that is coordinated, comprehensive, and includes and combines biomedical, behavioral,
and social interventions. HIV prevention science at NIH should be tied closely
to basic sciences and should offer practical, evidence-based strategies for
public health implementation.
An ideal comprehensive HIV prevention strategy includes three components:
behavioral and social interventions, biomedical technologies (e.g., sexually
transmitted disease treatments, topical microbicides, condoms, sterile needles
and syringes, and anti-addiction medications), and vaccines, integrated where
appropriate into a "combination"
approach analogous to anti-HIV combination therapy. The priority given by the
Working Group to vaccine development is described elsewhere in this document
(See II above). Therefore, this section highlights the priority of the biomedical
and behavioral approaches. The Working Group advocates coordination among all
three components.
Appropriate and effective prevention strategies require the organization
and application of fundamental knowledge in natural history, epidemiology,
and behavioral and social sciences into a coordinated and effective plan. Such
a plan should articulate research and intervention strategies that include
biomedical, behavioral, and social approaches. Led by the OAR, it should begin
with the coordination of activities across NIH, and then be coordinated with
plans of other U.S. agencies and those of other countries. The goal of this
HIV prevention science plan will be to identify and implement the most promising
methods for preventing sexual, parenteral, and perinatal transmission.
Three steps can be taken now to promote the coordination and visibility needed
for an HIV prevention science agenda: (1) an ongoing HIV Prevention Science
Advisory Committee convened by and reporting to the Director of the OAR; (2)
an HIV Prevention Science Coordinator charged with coordinating the implementation
of the NIH HIV prevention science agenda; and (3) an Initial Review Group devoted
to HIV prevention science proposals.
The HIV Prevention Science Advisory Committee should be co-chaired by a behavioral
scientist and a biomedical scientist and include distinguished non-governmental
scientists and appropriate representatives from the OAR and the ICDs with major
research interests in these areas. The Committee should advise the OAR Director
on the development and implementation of the HIV Prevention Science Agenda
and on the coordination of its agenda with the AIDS vaccine initiative.
There are high-priority scientific opportunities in the prevention science
area that would require an infusion of new funds.
Historically, the AIDS clinical trials effort attempted to respond to a diverse
set of needs and constituencies by forming several trials networks. NIAID,
which is the primary sponsor of NIH AIDS clinical trials, has a number of extramural
programs including the adult and pediatric AIDS Clinical Trials Groups (ACTGs),
the Community Programs for Clinical Research on AIDS (CPCRA), the Division
of AIDS Treatment Research Initiative (DATRI), and the Strategic Program for
Innovative Research on AIDS Therapy (SPIRAT). Other institutes sponsor additional
clinical trial efforts, including the NEI Study of the Ocular Complications
of AIDS (SOCA), the NINDS Neurologic AIDS Research Consortium, units that are
part of the NICHD pediatric ACTG, and the NCI AIDS Malignancy Consortium (AMC).
There also are substantial intramural trials efforts in NIAID and NCI.
Early extramural efforts, particularly at NIAID and NICHD, were highly directed
by institute staff. While this was appropriate when the first program was created
in 1986, the rapid maturation of the investigator community has obviated the
need for continued strong direction from NIH. Recent changes in the scientific
leadership and organizational structure in the ACTG and CPCRA appear to be
moving in the right direction; adequate time must be allotted to evaluate the
impact of these changes. In some instances, ICDs with an organ system or single
disease entity focus have structured independent clinical trials programs,
such as SOCA and AMC. While a sharp focus and specific expertise are brought
to such efforts, the resultant trials often fail to take into account the multi-system
nature of HIV infection and AIDS. Other institutes have confined their clinical
trials support to conducting subspeciality studies to exploratory, investigator-initiated
studies (NIDDK) or to support neurological trials within the ACTG (NINDS).
There has been overlap and, in some instances, unnecessary competition between
these diverse programs that are funded by different institutes with different
self-defined missions. The scientific productivity of the independent clinical
trials efforts has been quite variable, as has been the level of support and
enthusiasm from the funding institutes. For example, DATRI is viewed by the
Working Group to be an unsuccessful effort, with inadequate scientific input
from extramural investigators and limited productivity. Coordination of efforts
to achieve shared research goals, including exchange of ideas and the ability
to share data, has been difficult at best, even when programs have been managed
by the same institute staff. Attempts at collaborative research between programs
have been hampered by the lack of standardized databases. Similarly, the lack
of an organized repository for pathogens and clinical specimens from well-characterized
participants in trials has inhibited collaboration with basic scientists and
epidemiologist.
The Working Group believes that all NIH-sponsored clinical trials efforts
should be held to the highest standards for productivity and scientific excellence.
Programs that fail to meet these standards should be improved or eliminated.
To best address the present and future needs for therapeutics research in AIDS,
the Working Group recommends:
In this integrated network, scientific leadership should be provided by extramural
investigators, with support from institute staff. This proposed network should
include a broad range of potential sites and investigators with various levels
of expertise and scientific capability. It would replace the current ACTG,
CPCRA, DATRI, and possibly SPIRAT programs under the auspices of the NIAID.
This integrated network is envisioned as one with concentric layers of research
expertise and capability. Direct funding is required for the following essential
elements: an operations office that supports the central administrative and
scientific leadership of the group; a statistical center; the capacity to perform
sophisticated virologic and immunologic assays and to continue development
of new assays; and a core group of investigators/sites that can design and
perform Phase I/IIA and proof-of-concept studies, which require intensive patient
and laboratory monitoring. Also needed is a larger number of investigators
who can perform complex Phase IIB/III trials requiring intensive diagnostic
evaluation for clinical endpoints, close monitoring for toxicity, and facilities
for processing, storing and shipping of specimens for virologic, microbiologic,
and immunologic testing. These first two 'layers,' supported by grants, would
together provide the capability for initial exploratory studies and for advancing
this early work to Phase IIB/III studies. Existing Phase III programs, such
as SOCA, should be integrated into the core NIAID trials infrastructure. Existing
Phase I/IIA programs such as AMC, must be adequately funded to assess variables
relating to underlying HIV disease process; collaboration with the central
network for the conduct of Phase IIB-IV studies must be established.
The network described above must have the flexibility to meet the scientific
challenges of therapeutics research as they arise. A funding mechanism, such
as a master contract, that will permit rapid expansion and contraction of the
network's research units as the scientific need dictates is key. Such a mechanism
would ensure access to sufficient numbers of patients with diverse demographic
characteristics for Phase IV and some Phase III trials. In addition, individual
clinicians who meet specific criteria should have the opportunity to participate
in Phase IV trials on a protocol-by-protocol basis with capitated contractual
support. These large studies, evaluating fairly well-characterized agents and
requiring minimal data collection, need much less intensive clinical and toxicity
monitoring. The possibility for such expansion of the accessible patient and
investigator base will enable the network to successfully mount the large trials
needed to define strategies for optimal standard-of-care management.
For the optimal effectiveness of this clinical trials network, strong scientific
leadership must be exerted by the investigators. The system must be an open
one that entertains excellent research ideas from investigators regardless
of whether they are supported by network funds. This applies not only to proposals
for innovative clinical trials, but also to ideas for pathogenesis and translational
proof-of-concept research. A mechanism similar to a letter of intent could
be established so that independent, peer-reviewed research projects could utilize
the network's resources.
Collaborative research projects with other institutes involved in HIV/AIDS
clinical trials would permit optimal utilization of the network's scientific
and patient resources and must be encouraged. Building on the core trials infrastructure
provided by NIAID, each relevant institute should contribute scientific guidance
within its area of expertise, as well as supplementary funding for trials and
other resources (such as tissue banks and central reading centers), rather
than create anew the full capability to conduct comparative Phase III and IV
trials. Collaborative efforts can be expected to result in a more economical
use of NIH resources as well as the best possible science.
Uniform standards that apply at least to a minimal dataset of key baseline,
outcome, compliance, and toxicity data would permit cross-study analyses and
longitudinal follow-up of participants. Data-sharing capability will facilitate
collaboration and cooperation among AIDS Phase I/IIA and IIB-IV clinical trials
efforts. All future NIH trials should be subject to such standards.
The pediatric ACTG (PACTG) conducts all NIH-sponsored extramural AIDS clinical
trials in children. The PACTG is, at present, a conjoint effort that melded
two originally separate programs funded by NIAID and NICHD. The necessity to
integrate the two arose from the realization that there was a very limited
patient population available for enrollment into trials. Dual sponsorship utilizing
different funding mechanisms continues. The two groups are now integrated with
respect to scientific leadership.
The PACTG is to be congratulated for their successful demonstration that
AZT therapy of HIVinfected pregnant women and their newborns can reduce
substantially the risk of perinatal transmission. However, the PACTG has been
slow to initiate studies to identify even more effective interventions and
to exploit opportunities to define basic pathogenic mechanisms of pediatric
AIDS and analyze the effects of HIV infection on the developing immune system.
This may derive from a failure of the PACTG leadership to seek out external
scientific advice.
There are indications that prenatal HIV testing and the administration of
effective therapy are already affecting HIV transmission rates. If perinatal
transmission is successfully curtailed in the United States, the domestic pediatric
clinical trials effort will require careful re-examination. A timely consideration
of the optimal means to carry out clinical pediatric AIDS research in the future
is essential, particularly since the pediatric AIDS problem will continue to
grow worldwide. To maximize the productivity of domestic pediatric AIDS clinical
trials, the NCI intramural pediatric AIDS program should be interdigitated
with the PACTG. The Working Group believes that the pediatric AIDS clinical
trials program would benefit from outside advice.
In addition, the Working Group believes that, while pediatric trials are
understandably more expensive than those in adults, substantial savings can
be achieved without disrupting this effort.
To maximize the quality and productivity of all adult and pediatric clinical
trial activities sponsored by the NIH, the Working Group recommends:
This oversight committee will make recommendations to the OAR Director and
should be charged with developing an overall mission statement for NIH-sponsored
therapeutics research and with ensuring the coordination of all NIH-sponsored
HIV clinical trials efforts. It should be the responsibility of this group
to provide broad scientific direction, prevent unnecessary overlap and competition,
and identify the resources needed. The committee would focus primarily on inter-institute
issues. Certain activities now located within NIAID, such as the AIDS Clinical
Drug Development Committee that evaluates candidate therapies for inclusion
in NIAID clinical trials, might logically be assumed by this committee. The
oversight committee could then outline an overall NIH drug development plan
across institutes, networks and adult and pediatric populations. This group
should develop a policy regarding the performance of studies that are redundant
to industry efforts; NIH-sponsored trials programs should not study investigational
or marketed agents unless these studies will test novel hypotheses and would
not have otherwise been conducted by industry. NIH has funded clinical studies
that could be carried out equally well by pharmaceutical companies that could
profit significantly from positive outcomes. The Working Group believes that
such clinical studies should be conducted and financed by the companies unless
there are specific important objectives for either patient care or scientific
relevance that would otherwise be delayed or not carried out. In these instances,
co-funding by industry would be appropriate and should be explored.
The Working Group notes that the NIH Director recently created a committee
to determine what clinical research is appropriate for NIH sponsorship. In
this regard, the oversight committee should take its lead from the NIH-wide
policies being developed. This committee should be constituted as soon as possible,
so that it may guide the development of the proposed integrated network.
NIH drug discovery efforts encompass a wide range of scientific disciplines.
The Working Group and Drug Discovery Area Review Panel found marked differences
in the quality of research supported by AIDS funds. Some programs, such as
those focused on structural studies of HIV molecular targets and the National
Cooperative Drug Discovery Groups for OIs (NCDDG-OIs) are well organized and
productive. For instance, the Working Group found that the multidisciplinary
approach to determining the molecular structure of HIV-proteins supported by
the National Institute for General Medical Sciences (NIGMS) was exceedingly
successful, resulting in the characterization of a number of potential therapeutic
targets and agents. Such basic science efforts and others like it need continued
support and emphasis. The NIAID NCDDG-OIs has successfully developed agents
that have subsequently entered clinical trials. Other NIH drug development
programs could be improved and/or better coordinated. The Drug Discovery Area
Review Panel report makes detailed recommendations in specific areas.
In considering NIH's AIDS drug discovery efforts, some members of the Working
Group questioned whether having a program that replicates the functions of
the pharmaceutical industry is the best use of NIH resources. For example,
these members felt that NIH's proper scientific function is to support the
development of mechanism-based screens rather than support a screening program per
se. Certainly, research required to develop such screening assays is clearly
a high priority for NIH. There may be unique drug development situations that
require more extensive Federal support, particularly research on "orphan" diseases,
such as treatment of certain AIDS-associated OIs, where there is limited or
no commercial interest. The availability of NIH resources to support such drug
discovery research is certainly warranted.
One large endeavor, the NCI drug discovery program, located within the Developmental
Therapeutics Program (DTP), requires review and restructuring. The scope of
the DTP effort essentially replicates that found in the pharmaceutical industry:
resources are allocated for acquisition of natural and synthetic products,
screening, medicinal chemistry, synthesis, characterization of mechanism of
action, pharmacology and toxicology. Although this program identified active
agents in the mid-1980s when its cell-based antiviral screen was the only assay
available, DTP's continued dependence on this nonselective screen is no longer
warranted. Since the screen is not aimed at specific molecular targets, compounds
identified as active may have the same target as agents already well studied
in the clinic, as has been the case for the non-nucleoside reverse transcriptase
inhibitors identified by DTP. The few agents that have advanced to further
study represent a restricted number of antiviral mechanisms, and no truly novel
agent has reached the clinic. The overall program is rather diffuse, in spite
of the fact that day-to-day management of its many component branches, laboratories,
and contractors appears to be well integrated. As a result, the productivity
of this program over the last 8 years has been limited. Although the basic
research studies that have elucidated the mechanism of action of active compounds
have been of good quality, these studies have not met the goal of discovering
truly novel inhibitors of HIV.
The DTP program has a unique resource in its library of defined compounds
and in its various acquisition contracts, particularly for natural products.
The program also has substantial capabilities in medicinal chemistry, in the
characterization of drug mechanisms, and in the assessment of toxicology and
pharmacology sufficient to support the filing of an investigational new drug
(IND) application with the FDA. Because the pharmaceutical industry's continued
active interest in drug discovery for HIV and its associated OIs and malignancies
cannot be assured, maintenance of a drug discovery infrastructure supported
by NIH may be justifiable. However, resources would be better utilized if the
DTP's efforts were refocused on the development of novel mechanism-based screens
with high through-put capacity that are derived from basic research advances.
Moreover, the DTP should use its core resources to support NIH-wide antiretroviral
and opportunistic disease drug discovery research efforts; it would not be
cost-effective to reproduce the considerable DTP infrastructure in other ICDs.
Opportunistic infections (OIs) caused by a diverse range of viruses, fungi,
protozoa, bacteria and mycobacteria represent the major causes of suffering
and death for HIV-infected individuals. These pathogens can affect virtually
all tissues and organ systems, causing severe functional compromise, and in
some instances, malignant transformation. Although prophylactic regimens have
been defined that decrease substantially the risk of developing certain OIs,
none of these are completely successful and all are complicated by untoward
side effects; resistance development; interactions with other critical medications;
or significant inconvenience. Effective therapeutic strategies have been developed
to treat specific OIs once serious infection takes hold. However, none of these
therapies are curative and they are often toxic. Life-long suppressive therapy
is typically required following recovery from the acute disease presentation.
Cumulatively, these prophylactic and therapeutic advances have made significant
contributions to prolonging the lives of people with AIDS. Yet there remains
a great need to develop more effective and less toxic drugs to treat OIs for
which therapies are now available, and to develop effective treatments for
a number of OIs where none currently exist. Much of the progress made to date
in preventing and treating AIDS-associated OIs has come from the improved use
of drugs that had been developed previously to treat other infections, although
a limited number of new drugs has been developed specifically for use in HIV
disease. Advances in the treatment and prevention of AIDS-associated OIs has
also benefitted other immunocompromised patients.
Few new drugs have been developed specifically to treat OIs in people with
AIDS. There appears to be limited interest on the part of pharmaceutical companies
to support significant drug development efforts for a number of OIs that are
unique to or are most commonly seen as complications of AIDS.
NIH-sponsored researchers generate much of the basic science information
about the biology of the pathogens responsible for AIDS-associated OIs. Such
advances in our understanding of these pathogens will be needed for any successful
drug development effort. However, it is exceedingly difficult to advance basic
laboratory findings to the stages of drug development, manufacture, and initial
clinical evaluation. Should this situation continue, the Working Group is concerned
that the pace of development of new, more effective and less toxic therapies
to prevent and treat AIDS-associated OIs will be far too slow. Future progress
in preventing and treating AIDS-associated OIs will depend on progress in understanding
the fundamental biology and pathogenesis of these diseases. To best accomplish
this goal, investigators with expertise in microbiology, cell biology, genetics
and cancer biology should be encouraged to contribute to the study of AIDS-associated
OIs. As with all other areas of AIDS research, there is a great need to attract
and support young investigators in these areas.
The NIH currently supports a program of basic and applied research on OIs,
and the Working Group recommends an increase in the effort. It is expected
that the productivity of this effort will be enhanced significantly by the
recommendations discussed elsewhere in this report including: increased support
for investigator-initiated research; informing peer review groups of the scientific
priorities of the NIH Plan for HIV-Related Research; increased efforts to encourage
new and junior investigators to enter AIDS research; and increased efforts
to attract established investigators with expertise in related areas to pursue
AIDS-related research.
To enhance progress in this area, the OAR and relevant ICDs should increase
and better coordinate their efforts to foster research on AIDS-related OIs
and continue to solicit the advice of non-government scientists in identifying
new research needs and opportunities. As many of the AIDS-associated OIs also
cause disease in individuals with other types of immunodeficiency, and research
on these pathogens is consequently supported with both AIDS and non-AIDS funds,
it will be important to view the NIH portfolio in this area as defined by scientific
topic rather than funding mechanism.
In the course of the evaluation process, the issue of the appropriate role
of the NIH in facilitating the evaluation of CAM therapies for HIV infection
and its complications was considered. There are a number of reasons why attention
to this issue is important: CAM therapies are widely utilized by people with
HIV; they may have potential benefit; they may have potential harm; and the
perceptions of their efficacy may enhance or interfere with an individual's
use of "conventional" therapies for HIV disease.
Although the reasons are clear, a number of obstacles have confronted individuals
who have wanted to test the efficacy of specific CAM therapies. These obstacles
have limited progress in evaluating the potential benefits or dangers of CAM
therapies in widespread use. Advocates of CAM therapies for HIV disease have
argued that the NIH should institute a significant new research initiative
in this area, supported by substantial funding. Detractors have made the case
that it is simply not possible to test all agents presently being used by persons
with AIDS. To investigate these issues, the Working Group established a subpanel
of researchers and advocates interested in these issues and solicited input
from interested proponents of CAM therapies. Based on input received from these
sources, the Working Group believes that additional attention to this topic
is needed.
It is the view of the Working Group that the most meaningful and effective
action for the NIH to take to advance the study of the potential benefits or
harms of CAM use for HIV disease will be to strengthen the scientific basis
for future CAM research in HIV disease. An OAR effort toward this end should
be undertaken in close collaboration with the NIH Office of Alternative Medicine
(OAM), where significant expertise already exists concerning CAM research needs
and challenges. The Working Group therefore recommends that the following activities
be pursued:
Regional Primate Research Centers (RPRCs) are a critically important resource
for the scientific community. Nonhuman primates and the SIV/SHIV models
of infection are critical to testing drugs and vaccines, investigating the
mechanisms of infection and pathogenesis, and evaluating novel concepts for
interfering with virus infection and consequent disease progression. The use
of these model systems is an expensive but necessary part of many current research
projects. The importance of these systems will almost certainly continue to
grow in the future. To ensure the maximal productivity of research involving
non-human primates, it is essential that the most able scientists be supported
to conduct high-priority studies. However, it is the Working Group's view that
the current funding structure for research using primate models does not necessarily
support the most meritorious research. Currently, NIH AIDS support is distributed
to the RPRCs where it is used to support projects initiated and carried out
by investigators at the RPRC. There are many excellent investigators at the
RPRCs. Nonetheless, RPRC funds are not available for the support of non-RPRC
researchers who may have equally, if not more, deserving research proposals.
The inherent expense of research involving non-human primates makes it difficult
to obtain adequate support for projects involving these animals through the
R01 funding mechanism. Thus, the present NIH funding structure for primate
research does not permit all investigators with meritorious ideas equal access
to this scarce resource. To address these concerns, the Working Group recommends:
The goal of the panel will be to define mechanisms for the support of research
involving non-human primate models so as to provide equal access to all members
of the AIDS research community while maintaining the quality and vigor of the
RPRC programs. The panel also should provide advice on operational aspects
and infrastructure needs.
It is essential to maintain the quality of the infrastructure and animal
care activities carried out by the RPRC staffs. Even if funding to the RPRCs
must be increased to attain those goals, the Working Group feels that the benefit
in the quality of research obtained by these changes is worthwhile. The Working
Group recommends that the following approach be considered by this panel for
implementation in the near future:
Investigators interested in conducting experiments involving animals would
apply to the individual RPRCs for support derived from NCRR AIDS supplements.
These proposals would be reviewed by an external advisory committee at each
RPRC. Those projects deemed most worthy would be supported. At the time of
renewal of the RPRC grant, the review should place heavy emphasis on the RPRC's
success in attracting and supporting quality research studies. The panel recommended
above should investigate the possibility of providing seed funds to bring new,
non-RPRC investigators into RPRC-supported studies in the future.
The challenges posed by AIDS require both biomedical and behavioral interventions;
AIDS is a multi-system and multi-organ disease, involving malignancies, opportunistic
infections, neurological, gynecological, ocular, oral, dermatological and gastointestional
complications, affecting people across the life span from infancy to old age.
AIDS Research Centers can provide a central pool of resources, capable of a
flexible and coordinated response to new scientific opportunities. There are
many advantages to bringing together basic, clinical, epidemiological and behavioral
scientists in research centers. A central pool of resources provides the Center
with flexibility and allows a rapid and coordinated response to new scientific
opportunities. Translating basic laboratory and behavioral sciences research
into public health and clinical practice is an essential aspect of a Centers'
program that can, in turn, provide further basic research opportunities. Centers
also are ideal locations for interdisciplinary training, which can build upon
the academic and clinical strengths of an institution. In addition, Centers
have a greater capacity to leverage institutional donor and community support.
Currently, 16 AIDS Research Centers are funded by NIH. Twelve of these are
supported by the Centers for AIDS Research (CFARs) mechanism and four are supported
through the comprehensive research center mechanism. Of the CFARs, 11 are funded
by NIAID and one by NIMH. All 4 comprehensive AIDS research centers are funded
by NIMH. The CFAR programs were recently reviewed and recompeted. Weaker CFAR
programs have been eliminated, and current CFARs are viewed as generally productive,
but considerably hampered by a recent reduction in total funding per Center.
The Working Group considered the current levels of CFAR support to be, in many
instances, too low to build and maintain adequate infrastructure and core support.
The CFARs should have strong core facilities to support center-funded initiatives
and investigatorinitiated research grants. They also should have strong
community ties. The level of support for infrastructure and core facilities
of individual centers should be determined by a formula and be in proportion
to the Center's ability to obtain RO1 grants. Centers should maintain flexibility
to bring together interdisciplinary research. Incentives should be provided
to encourage epidemiological and behavioral research components at the centers.
The success of an AIDS center is dependent upon the caliber of its leadership,
the quality of its science, the integration of its programs, the ability to
foster collaborations, and the strength of its training and mentoring of scientists
around a common research theme. The leadership abilities of the center director
should be one of the key criteria in determining center support.
NIH research on HIV prevention, transmission, natural history, and treatment
has generated sizeable repositories of biomedical specimens and large databases
of information. Although these repositories and databases are potential national
research treasures, they currently are poorly coordinated, and many investigators
have little or no access to them. To be optimally used, repositories and databases
must be linked to an informative and readily accessible tracking system that
is widely available to the scientific community. Procedures for accessing samples
and data must be clearly delineated, fair, and peer-reviewed. Indeed, the Working
Group notes that some research networks are making progress in the development
of procedures for accessing specimens. Future development of repositories and
databases should be investigator-driven and prospectively-planned based on
cogent research hypotheses. Ideally, planning for repositories should involve
scientists knowledgeable in virology, immunology, and pathogenesis research
and should involve collaborations with clinicians and epidemiologists. This
would insure that appropriate specimens and data are collected and increase
the likelihood that they will be used. NIH should pursue linkages to privately-held
specimen repositories, such as those containing samples from industry-sponsored
clinical trials.
Throughout the course of the review, the Working Group, the six panels, and the component subpanels utilized a number of NIH database systems and the OAR AIDS Research Information System (ARIS) to secure AIDS-related grant and contract information and to gain a better understanding of the NIH AIDS portfolio. The Working Group recognizes that, while ARIS represents a unique NIH database, it must be improved. ARIS must contain all budget and relevant program information on every grant and contract coded as AIDS and AIDS-related.
The Working Group concluded that the NIH information databases were inadequate
to provide information for this review. The work of this evaluation was significantly
hampered by both the difficulty in obtaining information and the quality of
the information available from the databases. For many large programs listed
in ARIS, the only retrievable information provided to the system by the ICDs
was project number and funding level. Some projects were identified by the
ICDs only as "AIDS Research" or "Cancer Center," and thus
elusive to any analysis.
The Working Group concluded that the lack of a complete, accurate, and reliable
information database is simply an unacceptable situation that hampers the OAR
Director and the NIH Director from being able to fulfill their responsibilities
in directing, managing, and accounting for the AIDS-research portfolio. The
Working Group and the panels acknowledge and appreciate the considerable time
and effort from Institute and Center Directors and their staffs who worked
very hard to provide information for this review, filling the gaps from an
inadequate database system. However, the Working Group believes it is time
for the OAR and NIH to develop a more advanced and comprehensive information
system to track the entire NIH AIDS research portfolio, including both intramural
and extramural awards. The Working Group also realizes that an information
system will only be useful if all relevant information is provided to it by
the ICDs.
Information in the database should be regularly updated. This information
must be easily and readily retrievable by searching for any of the parameters
listed above and by research topic area. The ICD should assign an OAR Strategic
Planning code for each grant, contract or intramural project included in the
database. The OAR should periodically monitor and review the assigned strategic
plan codes to ensure that they adequately characterize the research conducted.
The Working Group's examination of information available from other existing
NIH databases revealed similar problems. OAR should develop a system to manage
NIH AIDS research project information that could serve as a model for NIH non-AIDS
information databases. It is essential that the AIDS and non-AIDS information
databases be compatible and have an identical information format so that they
provide an efficient means to obtain information critical in planning, budgeting,
managing, and evaluating NIH research programs.
In the review of the current NIH AIDS research programs, the Working Group
and Area Review Panels found that many ICDs have not developed an operational
definition of AIDS and AIDS-related research for the purposes of assigning
AIDS-designated funds. This has been a major issue encountered during the course
of the review.
The coding of projects as AIDS, AIDS-related, or non-AIDS currently is the
responsibility of each ICD; thus coding can vary according to the different
missions of the ICDs. Examples are noted throughout the individual panel reports
of projects that are inappropriately classified as AIDS or AIDS-related. In
some ICDs, most notably NCI, inappropriate classification has led to allocation
of AIDS research funds to activities with little or no direct relevance to
AIDS. Similarly, NHLBI-sponsored programs for the development of artificial
blood substitutes have been supported with AIDS research funds. Although such
research may be highly meritorious, supporting it with AIDS resources is inappropriate
since previous successful research has provided the means to protect the blood
supply from HIV.
The NCI, through leadership of its new Director, is currently developing,
in cooperation with the OAR, a coding system for AIDS and AIDS-related projects
that should result in a more accurate and reliable system for classification
of all NCI intramural and extramural programs and projects. Furthermore, the
NCI Director has recently announced the redirection of $30 million from intramural
research to fund new extramural research. This redirection of resources will
permit expansion of the NCI AIDS Malignancy Consortium. It will also allow
funding of many investigator-initiated AIDS research grants that had fallen
below the payline in other ICDs. The Working Group acknowledges NCI's example
as a model of how an ICD can begin to redress its historical problems of inappropriately
classifying research as AIDS-related.
The OAR and the ICDs should jointly develop definitions of AIDS and AIDS-related
research. These definitions should evolve with time and should not be viewed
as immutable. OAR should include definitions of AIDS and AIDS-related research
in the annual NIH Plan for AIDS-Related Research and should be responsible
for ensuring that the definitions are consistent among the various ICDs.
A second major issue in project coding relates to support for basic research.
Studies in the fields of molecular biology, structural biology, immunology,
and virology have provided the scientific foundation for rapid advances in
AIDS research. Support for basic research is crucial, as this research has
the potential to advance research on many diseases. However, the question remains,
how much basic biomedical and behavioral research should be supported with
AIDS research funds?
The Working Group and panels unanimously agreed that there is a crucial need
for a continued strong and viable OAR to provide overall scientific leadership
and coordination of NIH AIDS research. This endeavor requires vision and direction
that spans the scientific disciplines and institute missions.
The OAR budget authority for all intramural and extramural AIDS research, mandated by the NIH Revitalization Act of 1993, must be preserved. Anticipated budgetary constraints over the next
5 years will place even greater demand on the limited funding available for
AIDS research, thus making OAR's management and priority-setting roles even
more significant. OAR's authority to develop and implement the annual AIDS
research plan and budget is essential. OAR should increase its efforts to coordinate
AIDS research activities among the ICDs and with other agencies in order to
improve information exchange and eliminate duplication of efforts. OAR's collaborative
activities should also extend to private foundations, pharmaceutical and biotechnology
companies, and international agencies.
The Working Group acknowledges the continued support of the NIH Director
for the functions and authority of the OAR. The Working Group emphasizes that
the NIH Director's visible support is crucial for the implementation of the
recommendations of this report.
The Working Group recognizes this report and the accompanying Area Review Panel reports contain an extensive series of specific recommendations. We also recognize that major initiatives and programs often require up to 18 months to progress from a developmental stage to the actual awarding of grants and contracts. Therefore, it is imperative that an implementation plan be developed immediately so that these recommendations can be incorporated in the FY 1997 and
FY 1998 NIH AIDS research budget and planning processes.
The Evaluation Working Group and the six Area Review Panels were charged with reviewing, evaluating, and developing recommendations for the future of the NIH AIDS research program.
The program currently has a budget of approximately $1.4 billion and involves initiatives supported by virtually all ICDs. The NIH AIDS research portfolio spans basic, clinical, epidemiological, and behavioral research, as well as vaccines and drug development. It is funded through a range of mechanisms and is conducted by a diverse community of researchers representing a broad range of scientific disciplines.
In order to evaluate the NIH AIDS research program thoroughly, and to provide appropriate and useful recommendations for its future direction, it was necessary to involve individuals with both scientific expertise and familiarity with the NIH system. This included researchers, clinicians, activists, and service providers diverse in scientific discipline, institutional affiliation, geographic base, race/ethnicity, gender, and HIV serostatus (which was voluntarily self-revealed by some).
The 114 people involved in the review process came from government, universities,
private research institutions, community organizations, and pharmaceutical
and biotechnology companies.
It was recognized that with the appropriate expertise and familiarity comes
the likelihood that there is potential for bias and conflict of interest-both
perceived and real. In an effort to minimize such bias and conflict, a number
of steps were taken (similar to the process used by the National Academy of
Sciences and its affiliates). First, input was solicited from a wide range
of researchers as well as representatives of the infected and affected community
for nominees to serve on the Area Review Panels. The selection of Panel members
from resulting lists was based on expertise (both AIDS and non-AIDS) and familiarity
with HIV/AIDS issues, and was made by each Area Review Panel Chair in consultation
with the Working Group Chair. Every effort was made to balance the Panels with
individuals who represented different points of view and had different levels
of linkage to the NIH AIDS research program.
Second, at the initial meeting of the Working Group and the Area Review Panels, members were asked to declare their own potential biases and conflicts and to discuss these as a group. Third, individuals recused themselves from participating in activities that posed an obvious conflict
(e.g., serving on subpanels that reviewed programs that included their own
grants). Fourth, any reviews conducted by individuals or subpanels that could
be perceived to have a conflict were subject to secondary review by others
with no potential conflict. Finally, the reports generated by the individual
Panels and the Working Group were subject to lengthy discussion and debate
and were not finalized until consensus was reached.
ARNOLD J. LEVINE, Ph.D., Chair, is the Chairman and Harry C.
Weiss Professor of the Department of Molecular Biology at Princeton University,
and a member of the National Academy of Sciences and the Institute of Medicine.
He received his Ph.D. from the University of Pennsylvania and completed his
postdoctoral training at the California Institute of Technology. He is an eminent
researcher in virology-oncology, and author of over 277 scientific publications,
and the recipient of numerous awards, including the Bristol-Myers Squibb Award
for Distinguished Achievement in Cancer Research, the Ciba Drew Award in Biomedical
Research, the Shubitz Award from the University of Chicago Cancer Research
Center, the Thomas A. Edison Science Award, and the first annual Strang Award
from New York Hospital/Cornell Medical Center. In 1994, he was awarded the
Docteur Honoris Causa, University Pierre and Marie Curie, Paris.
HAROLD S. GINSBERG, M.D., Co-Chair, is an Expert Scientist
at NIAID, and the Eugene Higgins Professor of Medicine and Microbiology, Emeritus,
College of Physicians and Surgeons at Columbia University. He is a member of
the National Academy of Sciences and the Institute of Medicine. He serves on
the Board of Governors of the American Academy of Microbiology and the U.S.
National Committee for the International Union of Microbiological Societies.
He co-chaired the Institute of Medicine Roundtable for the Development of Drugs
and Vaccines Against AIDS and has chaired the NIH Ad Hoc AIDS Study Section.
He also has been a Vice President, International Committee for Nomenclature
of Viruses of the International Association of Microbiological Societies. Dr.
Ginsberg has received numerous awards, including the Senior U.S. Scientist,
Humboldt Award; the Physicians and Surgeons Distinguished Service Award; and
the Bristol-Myers Squibb Award for Distinguished Achievement in Infectious
Disease Research. He is an Honorary Fellow of the American Association for
the Advancement of Science and was a Fogarty International Scholar in 1992.
After graduating from the Tulane University School of Medicine, Dr. Ginsberg
served in World War II, achieving the rank of Lieutenant Colonel and was awarded
the Legion of Merit.
BARRY R. BLOOM, Ph.D., is an Investigator at the Howard Hughes Medical Institute and the Weinstock Professor of Microbiology and Immunology at the Albert Einstein College of Medicine in New York. He received his B.A. degree and an honorary Sc.D. from Amherst College, and his Ph.D. from the Rockefeller University. Dr. Bloom chaired the Tuberculosis Committee at WHO and is currently the Chair of the Scientific and Technical Advisory Committee to the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Dr. Bloom served as a consultant to the White House on International Health Policy during 1977-8. He has served as a member of the National Advisory Council of NIAID, its AIDS subcommittee, and the U.S. National Vaccine Advisory Committee. He is currently Co-Chair of the Board on International Health of the National Research Council of the National Academy of Sciences. He serves as a member of the WHO Ad Hoc Committee for Research Priorities and on the NAS Committee on Criteria for Federal Support of Federal Research and Development. In 1991, he received the first Bristol-Myers Squibb Award for Distinguished Research in Infectious Diseases. Dr. Bloom also is a member of the National Academy of Sciences, a member and Councillor of the Institute of Medicine, and a member of the American Academy of Arts and Sciences.
REBECCA H. BUCKLEY, M.D., is the J. Buren Sidbury Professor of Pediatrics
and the Chief of the Division of Pediatric Allergy and Immunology at the Duke
University Medical Center. She is an internationally known researcher with
a bibliography of over 200 scientific publications in the field of immunology,
specifically in the areas of normal and abnormal development of the immune
system, primary immunodeficiency diseases, and acquired immunodeficiency. Dr.
Buckley is a member of the American Association of Immunologists. She currently
is the Associate Editor of the Journal of Clinical Immunology. From 1984-1987,
she chaired its Clinical Immunology and Immunopathology awards committees.
Dr. Buckley has served on numerous advisory councils and committees, including
the Medical Advisory Committee of the Immune Deficiency Foundation, the Scientific
Advisory Committee of the Allergy and Immunology Institute of the International
Life Sciences Institute, and the Board of Scientific Counselors to the NIAID,
NIH.
CHARLES C.J. CARPENTER, M.D., is Professor of Medicine and Director
of the International Health Institute at Brown University; the President of
the Johns Hopkins Medical and Surgery Association; Chairman of the Section
on Medical Sciences, American Association for the Advancement of Science; Chairman
of the Office of AIDS Research Advisory Committee (OARAC); and Chairman of
the NIH Data Safety Monitoring Board for AIDS Clinical Trials Group. He is
a member of the Institute of Medicine and served on its Committee on Research
Grants and its Board of Science and Technology for International Development
and has chaired the Board of Governors for the American Board of Internal Medicine.
Dr. Carpenter has served on numerous NIH councils and committees. He has chaired
the AIDS Program Advisory Committee and the State-of-the-Art Conference on
AZT Therapy for Early HIV Infection, and has served as a member of the NIAID
Council and the Ad Hoc Consultants to the NIH AIDS Executive Committee. For
20 years he also served as a member of the WHO Expert Advisory Committee on
Bacterial Diseases, and he currently chairs the U.S. Delegation to the U.S.-Japan
Cooperative Medical Science Program.
DON C. DES JARLAIS, Ph.D., is the Director of Research of the Chemical
Dependency Institute at Beth Israel Medical Center, Professor of Epidemiology
and Social Medicine at Albert Einstein College of Medicine, and a Senior Research
Fellow at the National Development and Research Institute. He served as the
New York State Coordinator for AIDS Research and the Assistant Deputy Director
for AIDS Research Evaluation. As a leader in the fields of AIDS research and
intravenous drug use, his bibliography includes over 200 publications, and
he has made 1,000 presentations on AIDS and AIDS-related topics that include
the plenary addresses at the third and fourth International Conferences on
AIDS. He serves on numerous advisory committees for the CDC, NIDA, the National
Commission on AIDS, and the National Academy of Sciences. He is Vice Chair
of the Committee of AIDS Research and the Behavioral, Social, and Statistical
Sciences that was established by the National Research Council of the National
Academy of Sciences.
ANKE A. EHRHARDT, Ph.D., is the Principal Investigator and Director
of the HIV Center for Clinical and Behavioral Studies at the New York State
Psychiatric Institute and College of Physicians and Surgeons at Columbia University.
The Center was established in 1987 with a 5-year award by the NIMH and NIDA,
and received renewal in 1993 for a second 5-year term. Dr. Ehrhardt is a Research
Chief at the New York State Psychiatric Institute and a Professor of Medical
Psychology in the Department of Psychiatry at Columbia University. She is an
internationally known researcher in the field of sexual and gender development
of children, adolescents, and adults who has, over 25 years, amassed a bibliography
with 140 scientific publications. From 1962 to 1964, as a member of the Department
of Pediatrics at the University Medical School of Hamburg, West Germany, she
assessed and treated children and adolescents who were victims of incest. In
1964, she joined the Psychohormonal Research Unit at Johns Hopkins University
Hospital, under the direction of Dr. John Money. Dr. Ehrhardt, and Dr. Money
co-authored the book, Man and Woman, Boy and Girl in 1972. Since 1987,
Dr. Ehrhardt's research has included a wide range of studies on determinants
of sexual risk behavior among children, adolescents, heterosexual women and
men, the gay population, and on comprehensive approaches to prevention of HIV
and STD infection. She received an award by the State of New York for "Excellence
in Research" in 1990 and received the Distinguished Research Leadership
Award given by the American Psychological Association in 1996.
MARK HARRINGTON, a writer and AIDS activist, is a member of the Board
of Directors, Treatment Action Group (TAG); the Community Program Advisory
Committee of American Foundation for AIDS Research (AmFAR); and the Office
of AIDS Research Advisory Council for NIH (OARAC). A graduate of Harvard University,
Mr. Harrington has written extensively about clinical trials, therapies, opportunistic
infections, and related AIDS research issues in the New England Journal
of Medicine, Morbidity and Mortality Weekly Report, Journal of the American
Statistical Association, Journal of Acquired Immune Deficiency Syndromes, as
well as contributed to publications produced by ACT UP and TAG. He has served
as a consultant to the FDA Antiviral Drugs Advisory Committee and the AmFAR/CRI/CCC
Conference on "Organizing Community Based Clinical Trials: Models for
the AIDS Epidemic." He also has served on the NIH AIDS Clinical Trials
Group core committees for primary infections and opportunistic infections,
the NIH/FDA GP160 advisory panel, and the Public Health Service task forces
on prophylaxis and therapy for Mycobacterium avium complex and on antipneumocystis
prophylaxis for patients with HIV infection.
DAVID D. HO, M.D., is the Scientific Director and Chief Executive
Officer of the Aaron Diamond AIDS Research Center for the City of New York,
and Director of the Center for AIDS Research at the New York University School
of Medicine. He has held appointments as an Associate Professor of Medicine
at the UCLA School of Medicine and as a Physician and Research Scientist at
the Cedars-Sinai Medical Center and at the Harvard Medical School. Dr. Ho has
published over 117 scientific publications and serves on the editorial boards
of Cellular Immunology, Journal of Virology, Journal of Experimental
Medicine, and AIDS Research and Human Retroviruses. He is a member
of the Scientific Advisory Committees at Harvard University, Columbia University,
and the University of Colorado. He was a member of the President's National
Task Force on AIDS Drug Development and co-chaired its Drug Discovery subcommittee.
Dr. Ho has received numerous awards and honors, including the Scientific Award
of the Chinese American Medical Society, the New York Award for Excellence
in Science and Technology, the Ernst June Prize in Medicine, and the Legacy
Award from the Chinatown History Museum of New York. In 1994, he was elected
as a Fellow of the American Association for the Advancement of Science
KING HOLMES, M.D., Ph.D., Natural History, Epidemiology, and Biomedical
Prevention Area Review Panel Chair, is the Director of the Center for
AIDS and STDs, and Professor of Medicine, Epidemiology, and Microbiology
at the University of Washington, Seattle. Dr. Holmes received his M.D. from
Cornell University Medical College in 1963 and his Ph.D. in Microbiology
from the University of Hawaii, in 1967. He completed an internship in Internal
Medicine at Vanderbilt University, a residency in Medicine at the University
of Washington, and is board certified in Internal Medicine, with a Subspecialty
in Infectious Diseases. Dr. Holmes served as Head of the Division of Infectious
Diseases at the USPHS Hospital, Seattle, from 1970-1981, after which he joined
the CDC as Assistant to the Director of the Division of Sexually Transmitted
Diseases. From 1989-1990, Dr. Holmes was based at the Epidemiology Support
and Research Unit, Global Program on AIDS, World Health Foundation, Geneva.
He is a member of the Institute of Medicine.
KIYOSHI KUROMIYA has been the editor and publisher of a treatment
newsletter, Critical Path AIDS Project, since 1989. He operates a number
of cutting edge electronic services in Philadelphia, including a 24-hour AIDS
treatment hotline and computer BBS, a free Internet gateway, and a comprehensive
World Wide Web homepage on AIDS. He is a founding member of ACT UP/Philadelphia
and has been prominently active in civil rights, gay liberation, antiwar, and
human rights movements for 35 years. As a community constituency representative
of both the AIDS Clinical Trial Group and the Terry Beirn Community Programs
for Clinical Research on AIDS networks, he has long been an advocate for access
to treatments and treatment information (including both conventional and complementary
regimens) for underserved communities including Asian-Pacific Islanders and
other persons of color, incarcerated persons, and women. He serves on the faculty
of the AIDS Education Training Centers and serves on the National Advisory
Board of the National Minority AIDS Council and the advisory board for the
Health Cost and Services Utilization Study (HCSUS), a project of Rand Corporation
and the Agency for Health Care Policy and Research. Mr. Kuromiya also has been
active in Ryan White CARE Act programs on the local, state, and national levels.
MALCOLM A. MARTIN, M.D., is the Chief of the NIAID Laboratory of Molecular
Microbiology. During the past 20 years, Dr. Martin has focused his research
efforts on retroviruses and concentrated on HIV. His accomplishments include
the construction and dissemination of one of the most widely used full-length
molecular clones of HIV-1 (NLR-3), in which all of the viral genes are intact
and functional. In 1985, his group was the first to demonstrate that different
HIV-1 isolates are genetically distinct, and during the past decade, he has
published seminal papers describing the genetic analysis of HIV-1. More recently,
he has focused on HIV-1 vaccine and disease models in subhuman primates. Dr.
Martin has served on numerous NIH, USPHS, and WHO committees concerned with
AIDS, the safety of retroviral vectors, and the potential hazards attending
the administration of biologics. He has been honored with the NIH Director's
Award, the PHS Superior Service Award, the DHHS Distinguished Service Award,
and in 1990, a Presidential Executive Rank Award. He is a member of the Scientific
Review Boards of the Howard Hughes Medical Institute, the Lucille P. Markey
Charitable Trust, and the Aaron Diamond Foundation.
ROBERT TURNER SCHOOLEY, M.D., is the Chair of the AIDS Clinical Trials
Group Executive Committee and Director of the Colorado AIDS Clinical Trials
Unit. He also is Professor of Medicine and Head of the Infectious Disease Division
at the University of Colorado Health Sciences Centers. He previously was an
Associate Professor of Medicine at Harvard Medical School and Acting Director
of the Harvard AIDS Clinical Trials Unit at Massachusetts General Hospital.
Dr. Schooley received his M.D. from Johns Hopkins University and performed
research at NIH, where he became the Chief Clinical Associate of the NIAID
Laboratory of Clinical Investigation. His research has focused on retrovirology
and immunodeficiency viruses, and he has authored a bibliography of over 146
scientific publications. Dr. Schooley has served as a consultant and Chair
of NIH study sections for retrovirology and was a member of the DHHS Task Force
on AIDS Drug Development.
PHILLIP A. SHARP, Ph.D., is the Director of the Center for Cancer
Research, the Salvador E. Luria Professor, and the Chair of the Department
of Biology at the Massachusetts Institute of Technology. Dr. Sharp's research
interests have centered on the molecular biology of tumor viruses and the mechanisms
of RNA splicing. His work provided one of the first indications of the startling
phenomenon of "split genes" in the cells of mammals that is crucial
for understanding the genetic causes of cancer. For this work, Dr. Sharp shared
the 1993 Nobel Prize in Physiology or Medicine with Dr. Richard Roberts. His
other awards include the General Motors Research Foundation's Alfred P. Sloan,
Jr., Prize for Cancer Research; the Louisa Gross Horwitz Prize; the Albert
Lasker Basic Medical Research Award; the Gairdner Foundation International
Award of Canada; and the MIT Faculty Achievement Award. In 1991, his alma mater,
Union College, awarded him an honorary degree of Doctor of Human Letters. Dr.
Sharp has a distinguished record of public service, which includes having served
as a member of the President's Advisory Council on Science and Technology.
He co-chaired the committee that produced the Director of NIH's Strategic Plan
and served on the Committee on Science, Engineering, and Public Policy (COSEPOP),
and the Search Committees for the Directors of the National Center for Human
Genome Research and the Office of AIDS Research. In the course of his 20-year
scientific/academic career, Dr. Sharp has been a devoted educator/mentor and
has trained more than 60 postgraduate and graduate students.
P. ROY VAGELOS, M.D., is the former Chief Executive Officer of Merck & Company,
Inc., where he served in this position for 9 years, and was Chairman from 1986
to 1994. Earlier, he served as Chairman of the Department of Biological Chemistry
and Director of the Division of Biology and Biomedical Sciences at Washington
University in St. Louis. After completing his residency at Massachusetts General
Hospital, Dr. Vagelos was a Senior Surgeon and then the Section Head of the
Comparative Biochemistry Branch at the National Heart Institute. The author
of more than 100 scientific papers, Dr. Vagelos received the Enzyme Chemistry
Award of the American Chemical Society in 1967. He is a member of the National
Academy of Sciences, the American Academy of Arts and Sciences, and the American
Philosophical Society. He has received honorary Doctor of Science degrees from
Washington University, Brown University, the University of Medicine and Dentistry
of New Jersey, New York University, Columbia University, and the New Jersey
Institute of Technology, an honorary Doctor of Laws degree from Princeton University,
and an honorary Doctor of Human Letters from Rutgers University. Dr. Vagelos
is a Director of the Prudential Insurance Company of America, PepsiCo, Inc.,
McDonnell Douglas Corporation, and the Estee Lauder Companies, Inc. He also
is the Chairman of the board of Trustees of the University of Pennsylvania
and a Trustee of The Danforth Foundation.
RICHARD J. WHITLEY, M.D., Clinical Trials Area Review Panel Chair,
is the Loeb Eminent Scholar Chair in Pediatrics, Vice Chairman in the Department
of Pediatrics, Associate Director in the Center for AIDS Research, and a Scientist
in the Cancer Research and Training Center at the University of Alabama at
Birmingham. His numerous awards and honors include membership in the Society
for Pediatric Research, the Infectious Diseases Society, and the 1991 Award
for Excellence in Pediatric Research by the American Academy of Pediatrics.
In 1991, he also was named to be the Canon Ely Lecturer at the Harvard School
of Medicine, Children's Hospital, in Boston, Massachusetts. His many professional
memberships include the American Society for Microbiology, the American Society
for Virology, the Pediatric Infectious Diseases Society, and the International
Society for Antiviral Research. Dr. Whitley has served on numerous national
and international committees, including several NIH committees. He has made
significant contributions to the scientific literature and has produced an
exhaustive list of more than 370 journal articles, book chapters, editorials,
and abstracts, in addition to editing and co-editing several important medical
books on infections and viral diseases.
DAVID BALTIMORE, Ph.D., is the American Cancer Research Professor,
the Ivan R. Cottrell Professor of Molecular Biology and Immunology, and Institute
Professor at the Massachusetts Institute of Technology. He is a member of the
Office of AIDS Research Advisory Council (OARAC), the Board of Directors of
the Dibner Institute for the History of Science and Technology, and the Scientific
Advisory Committee at Children's Hospital. He has served on the ad hoc committee
to review the National Cancer Institute, and on the basic research subcommittee
of the NIAID AIDS Research Advisory Committee. He also has served as the Chairman
of the Board of Trustees at the Scientists Institute for Public Information,
and has been a member of the Hewlett-Packard Laboratories Research Board and
their Board of Governors in addition to being a member of the AIDS Oversight
Committee of the Institute of Medicine, and the Scientific Advisory Board of
the Massachusetts General Hospital Cancer Center. Dr. Baltimore is an internationally
known researcher with a bibliography of over 500 scientific publications. He
has been elected a member of the American Academy of Arts and Sciences, the
Pontifical Academy of Sciences, the American Medical Writers Association, Foreign
Member, The Royal Society, the Institute of Medicine, the Japanese Biochemical
Society, and the American Academy of Microbiology. In 1975, he received the
Nobel Prize in Physiology or Medicine.
King Holmes, M.D., Ph.D. Chair
Professor of Medicine
Professor of Epidemiology and Microbiology
Director, Center for AIDS and STDs
University of Washington
Moises Agosto
Director
Research and Treatment Advocacy
National Minority AIDS Council
Susan Buchbinder, M.D.
Chief, Research Branch
San Francisco AIDS Office
Victoria Cargill, M.D.
Associate Professor of Medicine
University Hospital of Cleveland
Willard Cates, Jr., M.D., M.P.H.
Corporate Director, Medical Affairs
Family Health International
Margaret A. Chesney, Ph.D.
Professor
Department of Medicine
School of Medicine
University of California at San Francisco
Samuel R. Friedman, Ph.D.
Principal Investigator
National Development and Research
Institute Incorporated
Richard A. Kaslow, M.D., MPH
Professor, Departments of Epidemiology, Medicine and Microbiology
University of Alabama at Birmingham
Robert S. Klein, M.D.
Attending Physician
Montefiore Medical Center
Marie Laga, M.D., Ph.D.
Head, Epidemiology and Intervention Section
Department of Microbiology
Center for AIDS and STD
Institute of Tropical Medicine (BELGIUM)
Michelle Murrain, Ph.D.
Associate Professor of Neurobiology
School of Natural Sciences
Hampshire College
Nancy Padian, Ph.D.
Associate Adjunct Professor
Department of Ob-Gyn and Reproductive Sciences
San Francisco General Hospital
John Phair, M.D.
Chief of Infectious Diseases
Department of Medicine
Northwestern University
Medical School
Steven G. Self, Ph.D.
Head, Program in Biostatistics
Fred Hutchinson Cancer Center
Sten Vermund, M.D., Ph.D.
Chair, Department of Epidemiology
School of Public Health
University of Alabama at Birmingham
Robert Wood, M.D.
Director, AIDS Control Program
AIDS Project
Ashley T. Haase, M.D.
Chair
Head, Department of Microbiology
University of Minnesota
Hospital Center
Rafi Ahmed, Ph.D.
Professor
Department of Microbiology and Immunology
University of California
Richard B. Gaynor, M.D.
Professor of Medicine and Microbiology
University of Texas
Gregg Gonsalves
Treatment Action Group
Stephen Harrison, Ph.D.
Department of Biochemistry and Molecular Biology
Harvard University
Howard Hughes Medical Institute
Diane E. Griffin, M.D., Ph.D.
Professor and Chair
Molecular Microbiology and Immunology
Johns Hopkins University
School of Hygiene and Public Health
Richard A. Koup, M.D.
Staff Investigator
Aaron Diamond AIDS Research Center
Norman L. Letvin, M.D.
Chief
Division of Viral Pathogenesis
Harvard Medical School
Beth Israel Hospital
George Miller, M.D.
John F. Enders
Professor of Pediatric Infectious Diseases
Professor of Epidemiology and
Molecular Biophysics and Biochemistry
Yale University School of Medicine
Bruce S. Rabin, M.D., Ph.D.
Professor of Pathology and Psychiatry
Department of Clinical Immunopathology
University of Pittsburgh Medical Center
George Shaw, M.D., Ph.D.
Professor of Medicine and Microbiology
University of Alabama at Birmingham
Mario Stevenson, Ph.D.
Professor of Pathology and Microbiology
University of Nebraska Medical Center
Bruce D. Walker, M.D.
Associate Professor of Medicine
Massachusetts General Hospital
Harvard Medical School
Irving L. Weissman, M.D.
Professor of Pathology/Developmental Biology
Department of Pathology
Stanford University School of Medicine
Steven M. Wolinsky, M.D.
Associate Professor
Division of Infectious Diseases
Northwestern University
Emilio A. Emini, Ph.D.
Chair
Executive Director
Department of Antiviral Research
Merck Research Laboratories
John M. Coffin, Ph.D.
American Cancer Society Research Professor
Department of Molecular Biology and Microbiology
Tufts University School of Medicine
Bill Current, Ph.D.
Senior Research Scientist
Eli Lilly and Company
Alan D. Frankel, Ph.D.
Assistant Investigator
University of California, S.F. Department of Biochemistry and Biophysics
James M. Hogle, Ph.D.
Edward S. Harkness Professor
Harvard University
Brenda Lein
Director, Information and Advocacy
Project Inform
Judy Lieberman, M.D., Ph.D.
Assistant Professor of Medicine
Harvard University
Richard Lynn, M.D.
Director
Pfizer Pharmaceutical
Joseph M. McCune, M.D., Ph.D.
Associate Investigator
Gladstone Institute of Virology and Immunology
Richard Mulligan, Ph.D.
Professor of Molecular Biology
Fomatix
Manuel Navia, Ph.D.
Vice President and Senior Scientist
Vertex Pharmaceuticals
John Secrist, Ph.D.
Executive Vice President
Southern Research Institute
Richard R. Tidwell, Ph.D.
Professor of Pathology
University of North Carolina
Dani P. Bolognesi, M.D.
Chair
James P. Duke Professor
Department of Surgery
Duke University Medical School
Abul K. Abbas, M.D.
Professor of Pathology
Department of Pathology
Harvard Medical School
Brigham and Women's Hospital
Lawrence Corey, M.D.
Head, Virology Division
Professor of Laboratory Medicine, Microbiology & Medicine
University of Washington
Pacific Medical Center
Ronald C. Desrosiers, Ph.D.
Professor
Microbiology and Molecular Genetics
New England Primate Research Center
Ellen Heber-Katz, Ph.D.
Professor
Wistar Institute
Maurice R. Hilleman, Ph.D., D.Sc.
Director
Merck Institute for Therapeutic Research
Merck Research Laboratories
Jiri Mestecky, M.D.
Professor of Microbiology and Medicine
Department of Microbiology
University of Alabama, Birmingham
John Moore, Ph.D.
Associate Professor of Microbiology
New York University School of Medicine
Staff Investigator
Aaron Diamond AIDS Research Center
James I. Mullins, Ph.D.
Professor
Departments of Microbiology and Medicine, University of Washington
Harriet L. Robinson, Ph.D.
Professor of Pathology
Department of Pathology
University of Massachusetts Medical Center
William Snow
ACT UP/Golden Gate
Kathelyn S. Steimer, Ph.D.
Director
Department of Viral Immunobiology
The Biocene Company/Chiron Corporation
Ralph Steinman, M.D.
Professor
Laboratory of Cell Physiology and Immunology
Rockefeller University
Cladd Stevens, M.D., M.P.H.
Head
Laboratory of Epidemiology
New York Blood Center
Craig Thompson, M.D.
University of Chicago
Peter F. Wright, M.D.
Head
Department of Pediatric Infectious Disease
Richard J. Whitley, M.D.
Chair
LOEB Eminent Scholar Chair in Pediatrics
Professor of Pediatrics, Microbiology and Medicine
University of Alabama at Birmingham
Department of Pediatrics
Richard F. Ambinder, M.D., Ph.D.
Johns Hopkins Oncology Center
Arthur Amman, MD
Ariel Project
Pediatric AIDS Foundation
Dawn Averitt-Doherty
Executive Director, WISE
William Bahlman
ACT-UP New York
Edward Connor, M.D.
Medimunne Inc.
Deborah Cotton, M.D., M.P.H.
Assistant Professor of Medicine
Harvard Medical School
Infectious Disease Unit
Massachusetts General Hospital
Spencer Cox
Chair, Antivirial Committee
Treatment Action Group
Janet Darbyshire, M.B.C.hB, F.R.C.P., M.Sc.
Medical Research Council UCLMS
Lynda Dee, Esquire
Executive Director
AIDS Action Baltimore, Inc.
David L. DeMets, Ph.D.
Department of Biostatistics
University of Wisconsin
Wafa El-Sadr, M.D., M.P.H.
Director
Division of Infectious Diseases
Harlem Hospital
John Martin, Ph.D.
Executive Vice President for Research and Development
Gilead Sciences
Julio Montaner, M.D.
Canadian HIV Trials Network
Maureen W. Myers, Ph.D.
Clinical Program Director
Boehringer Ingelheim
Pharmaceuticals, Inc.
Roger J. Pomerantz, M.D.
Professor of Medicine
Director
Division of Infectious Diseases
Thomas Jefferson University
William G. Powderly, M.D.
Associate Professor of Medicine
Department of Infectious Diseases Washington University
Peter Reiss, M.D., Ph.D.
Acting Director
National AIDS Therapy
Evaluation Center
Department of Internal Medicine
Academic Medical Center
Douglas D. Richman, M.D.
Professor
Departments of Pathology and Medicine, 0679
University of California, San Diego
Mark Wainberg, M.D.
Chairman, Director
McGill University AIDS Center
Professor of Medicine and Microbiology
McGill University
Head, AIDS Research Laboratory
Lady Davis Institute
Jewish General Hospital
Catherine Wilfert, M.D.
Professor of Pediatrics
Pediatrics Department
Duke University Medical Center
Brian Wong, M.D.
Chief, Infectious Diseases
VA Connecticut Health Care System
Christina M. Marra, M.D.
Assistant Professor of Medicine
(Neurology)
Division of Neurology & Infectious Diseases
Harborview Medical Center
Didier Trono, M.D.
Assistant Professor
The Salk Institute for Biological Studies
Thomas J. Coates, Ph.D.
Chair
Director
Center for AIDS Prevention Studies
University of California, San Francisco
John Bancroft, M.D.
Director
Kinsey Institute
Indiana University
Floyd E. Bloom, M.D.
Chairman
Department of Neuropharmacology
The Scripps Research Institute
Sherry Deren, Ph.D.
Director
Institute for AIDS Research
National Development and Research Institutes
Rafael M. Diaz, Ph.D.
Associate Professor
Center for AIDS Prevention Studies
University of California, San Francisco
Ferd Eggan
AIDS Coordinator, City of Los Angeles
Loretta S. Jemmott, Ph.D., R.N., F.A.A.N.
Associate Professor
University of Pennsylvania
School of Nursing
(Resigned, September 25, 1995)
Jeffrey A. Kelly, Ph.D.
Director
Center for AIDS Intervention Research
Medical College of Wisconsin
Judith A. Levy, Ph.D.
Associate Professor, University of Illinois, Chicago, School of Public Health
Michael Merson, M.D.
Dean of Public Health
Chairman
Department of Epidemiology and Public Health
Yale University School of Medicine
Richard W. Price, M.D.
Professor, Department of Neurology
San Francisco General Hospital
Mike Shriver
Executive Director
Mobilization Against AIDS
Freya Sonenstein, Ph.D.
Director
Population Studies Center
The Urban Institute
Ezra Susser, M.D., Dr.P.H.
Associate Director
HIV Center
New York State Psychiatric Institute and Columbia University
Wayne Jonas, M.D., Co-Chair
Director, Office of Alternative Medicine
NIH
Kiyoshi Kuromiya, Co-Chair
Critical Path Project
NIH AIDS Evaluation Working Group
Donald Abrams, M.D.
Professor of Medicine
University of California
Assistant Director, AIDS Program
San Francisco General Hospital
Ronald Baker, Ph.D.
Director, Treatment Education and Advocacy
San Francisco AIDS Foundation
Carola Burroughs
Holistic Connections
Misha Cohen, OMD
Chinese Herbalist
Leonard Herzenberg, Ph.D.
Professor of Genetics
Department of Genetics
Stanford University
John James
Editor and Publisher
AIDS Treatment News
Michael Onstott
West Coast Coordinator
National AIDS Nutrient Bank
Mary Romeyn, M.D.
San Francisco, CA
Leanna Standish, N.D., Ph.D.
Director
AIDS Research Center
Bastyr University
Emilio A. Emini, Ph.D.
Executive Director
Department of Antiviral Research
Merck Research Laboratories
Norman L. Letvin, M.D.
Chief, Division of Viral Pathogenesis
Harvard Medical School
Beth Israel Hospital
Bill Current, Ph.D.
Senior Research Scientist
Eli Lilly and Company
Joseph M. McCune, M.D., Ph.D.
Associate Investigator
University of California-San Francisco
Gladstone Institute of Virology and Immunology
San Francisco, California
Ashley T. Haase, M.D.
Head, Department of Microbiology
University of Minnesota Hospital Center
Diane E. Griffin, M.D., Ph.D.
Professor and Chair
Molecular Microbiology and Immunology
Johns Hopkins University
School of Hygiene and Public Health
Anke A. Ehrhardt, Ph.D.
Director
HIV Center for Clinical and Behavioral Studies
Professor of Clinical Psychology
Department of Psychiatry
Columbia University College of Physicians and Surgeons
Harold S. Ginsberg, M.D.
Professor Emeritus
Departments of Microbiology and Medicine
Columbia University College of Physicians and Surgeons
and
Expert Scientist
National Institute of Allergy and Infectious Disease
National Institutes of Health
David Ho, M.D.
Director
Aaron Diamond AIDS Research Center
King Holmes, M.D., Ph.D.
Director
Center AIDS and STDs
University Washington
Harold Ginsberg, M.D., Chair
Expert, NIAID, LID, IDVS
Viral Subgroup
Edward Mocarski, Ph.D., Subgroup Chair
Professor & Chair
Department of Microbiology & Immunology
Stanford University School of Medicine
Don Coen, Ph.D.
Professor
Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Carlton Hogan
Community Programs for Clinical
Research on AIDS Statistical Center
Coordinating Center for Biometric Research
Division of Biostatistics, School of Public Health
University of Minnesota
James Hogle, Ph.D.
Edward S. Harkness Professor
Harvard University
Earl Kern, Ph.D.
Research Professor
Pediatrics Department
University of Alabama at Birmingham
George Miller, M.D.
John F. Enders Professor of Pediatric Infectious Diseases
Professor of Epidemiology and Molecular
Biophysics and Biochemistry
Department of Pediatrics
Yale University School of Medicine
Larry Stanberry, M.D., Ph.D.
Director
Division of Infectious Diseases
Children's Hospital Medical Center Cincinnati
Fungal Subgroup
Peggy Hostetter, M.D., Subgroup Chair
Head
Division of Infectious Diseases
Professor of Pediatrics
University of Minnesota Medical School
George Deepe, Jr., M.D.
Professor
Division of Infectious Diseases
University of Cincinnati College of
Medicine
Jack Edwards, M.D.
Chief
Division of Infectious Diseases
Harbor Medical Center
Jerry Fink, Ph.D.
American Cancer Society
Professor of Genetics
Whitehead Institute, Cambridge
John Perfect, M.D.
Associate Professor of Medicine
Duke University Medical Center, Durham
PCP Subgroup
Melanie Cushion, Ph.D., Subgroup
Chair
Associate Professor of Medicine
Department of Infectious Diseases
University of Cincinnati
College of Medicine/VAMC
Marilyn Bartlett, M.S.
Professor of Pathology
Department of Clinical
Microbiology/Pathology
Indiana University School of Medicine
Richard Tidwell, Ph.D.
Professor of Pathology
University of North Carolina
Toxo/Enteric Protozoa Subgroup
Charles Sterling, Ph.D., Subgroup Chair
Professor
Department of Veterinary Science
William Current, Ph.D.
Senior Research Scientist, Eli Lilly & Company
Keith Joiner, M.D.
Professor of Medicine
Yale University School of Medicine
Mycobacteria Subgroup
Jerrold Ellner, M.D., Subgroup Chair
Director
Division of Infectious Diseases
Department of Medicine
Case Western Reserve University
Barry Bloom, Ph.D.
Albert Einstein College of Medicine
Carlton Hogan
Community Programs for Clinical Research on AIDS Statistical Center
Coordinating Center for Biometric Research
Division of Biostatistics, School of Public Health
University of Minnesota
William Jacobs, Ph.D.
Associate Investigator
Howard Hughes Institute
Associate Professor of Microbiology & Immunology
Albert Einstein College of Medicine
Emerging Pathogens Subgroup
David Relman, M.D., Subgroup Chair
Assistant Professor of Medicine and
Microbiology & Immunology
Palo Alto VA Medical Center
Associate Professor
College of Physicians & Surgeons of Columbia University
Division of Neuropathology
Stan Falkow, Ph.D.
Professor of Microbiology and Medicine
Department of Microbiology & Immunology
Stanford University School of Medicine
Richard Locksley, M.D.
Associate Professor
Department of Medicine
Ad Hoc Subpanel Member
Eric Hunter, Ph.D.
Director
UAB AIDS Center
University of Alabama, Birmingham
Dr. Alberto Advendano, Director, Health and Treatment Program of the National
Association of
People with AIDS (NAPWA)
David Young Allen, private citizen
Dr. Duane Alexander, Director, National Institute of Child Health and Human Development, NIH
Bill Bahlman, Founding Member, ACT UP New York Treatment and Data Committee
Dr. Samuel Baron, University of Texas Medical School at Galveston, Department of Microbiology
Dr. Fred Bingham, Executive Director, Direct AIDS Alternative Information Resources (DAAIR)
Lloyd Blake, private citizen
Carola Burroughs, Holistic Health Educator and Consultant
Keith Burroughs, Youth Health Empowerment of Philadelphia
George Carter, ACT UP, New York
Teresa Chavez, private citizen
Dr. Joseph Coggin, Jr., University of South Alabama, Department of Microbiology
and
Immunology
Dr. Rex Cowdry, Acting Director, National Institute of Mental Health, NIH
Julie Davids, ACT UP, Philadelphia
Dr. Jim Davis, private citizen
Paul Davis, ACT UP, Philadelphia
Martin Delaney, Founding Director, Project Inform, San Francisco
Kathy DeLeon, Native American AIDS Caucus of New York
Dr. Carl Dieffenbach, Acting Associate Director, Basic Sciences Program,
National Institute of
Allergy and Infectious Diseases, NIH
Dr. Jerry Dodgson, Michigan State University, Department of Microbiology
Dr. Anthony Fauci, Director, National Institute of Allergy and Infectious Diseases, NIH
Anna Forbes, AIDS and Women's Health Policy Consultant
Dr. Hassan James Gibbs, We the People and the Galaei Project, Philadelphia
Dr. Joseph Glorioso, University of Pittsburgh School of Medicine, Department
of Molecular
Genetics and Biochemistry
Dr. Karl Goodkin, University of Miami School of Medicine
Dr. Arthur Gottlieb, Professor of Medicine and Chairman, Department of Microbiology
and
Immunology, Tulane University School of Medicine
Dr. Harold Greenspan, private citizen
Jamie Gross, ACT UP, New York
Gabriel Guimares, Opera Director
Dr. David J. Hentges, Texas Tech University Health Sciences Center, Department of Microbiology
Dr. Rita H. Hindin, University of Massachusetts, Amherst
Dr. Penny Hitchcock, Chief, Sexually Transmitted Diseases Branch, Division
of Microbiology and
Infectious Diseases, National Institute of Allergy and Infectious Diseases,
NIH
Dr. Margaret Holmes, Chief, Cancer Centers Branch, National Cancer Institute, NIH
Dr. Eric Hunter, University of Alabama AIDS Center
Dr. Susan Jackson, University of Alabama Microbiology Graduate Program
Dr. Jeffrey Kelly, private citizen
Dr. Jack Killen, Director, Division of AIDS, National Institute of Allergy
and Infectious Diseases,
NIH
Dr. Richard Klausner, Director, National Cancer Institute, NIH
Bob Lederer, Direct AIDS Alternative Information Resources, New York
Dr. Claude Lenfant, Director, National Heart, Lung, and Blood Institute, NIH
Dr. Alan Leshner, Director, National Institute on Drug Abuse, NIH
Michelle Lopez, private citizen
Dr. Ronald Luftig, Louisiana State University Medical Center, Department
of Microbiology,
Immunology and Parasitology
Mary Lucey, HIV Activist
Dr. Thomas McDonald, University of Nebraska Medical Center, Department of
Pathology and
Microbiology
Mary Menendez, private citizen
Mark Milano, ACT UP, New York
David Miller, ACT UP, New York, and Interfaith Living With AIDS Project Collective, New York
Dr. Steven Mizel, Bowman Gray School of Medicine of Wake Forest University
Kaiya Montaoceaw, Center for Natural and Traditional Medicines
Dr. Ron Montelaro, University of Pittsburgh School of Medicine
Neal Nathanson, M.D., University of Pennsylvania, Department of Microbiology,
School of
Medicine
Ann Northrup, ACT UP, HIV AIDS Educator
John Perrino, ACT UP, New York
Mr. Omar Perez, Health and Treatment Program of the National Association
of People with AIDS
(NAPWA)
Nina Reznick, private citizen
Bernard Roizman, Sc.D., University of Chicago, Majorie B. Kovler Viral Oncology Laboratories
Dr. Fritz Rottman, Case Western Reserve University, Department of Molecular
Biology and
Microbiology, School of Medicine
Mike Ruff, Georgetown University School of Medicine
Fred Schaich, Founding Director, International Foundation for Alternative
Research in AIDS
(IFARA)
Dr. Saul Silverstein, Columbia University Department of Microbiology, College
of Physicians and
Surgeons
Dr. Magdalene So, Oregon Health Sciences University, Department of Microbiology
and
Immunology
Kate Sorenson, ACT UP, Philadelphia
Dr. Leanna Standish, AIDS Research Center, Bastyr University, Seattle
Andy Stettner, ACT UP, New York
Dr. Ellen Stover, Director, Office on AIDS, National Institute of Mental Health, NIH
Norberto Stuart, ACT UP
Dr. Ronald Swanstrom, Lineberger Comprehensive Cancer Center, University
of North Carolina
Chuck Thomas, Marijuana Policy Project of Washington, DC
Orlando Torres, private citizen
Dr. Judith Vaitukaitis, Director, National Center for Research Resources, NIH
Dr. Harold Varmus, Director, National Institutes of Health
Dr. Gregory A. Vigilianti, Boston University, Department of Microbiology
Dr. Caroline Whitacre, Ohio State University, Department of Medical Microbiology
and
Immunology
Diana Williamson, M.D., Mt. Sinai Medical Center, New York, New York
Dr. Anne Willoughby, Chief, Pediatric, Adolescent and Maternal AIDS Branch,
National Institute of
Child Health and Human Development, NIH
Dr. Maxine Wolfe, City University of New York
Rev. Brother James E. duPont Wortman, Homeward Bound, Philadelphia
Jeanmarie Zippo, Nurse Specialist, ActionAIDS, Philadelphia