AIDS Research
The research programs of the NCI have been at the forefront of progress
against AIDS ever since the epidemic was first identified. Research into
the fundamental biology of HIV and AIDS, AIDS treatment and, in particular,
AIDS-related malignancies takes place throughout all programmatic mechanisms
of the NCI. The NCI, in coordination with all of the other Institutes and
the NIH Office of AIDS Research, continues its commitment to this important
challenge and is working to ensure integration of NCI-supported AIDS and
AIDS-related research with national AIDS strategies. Many of the areas of
fundamental biology that are developed in the NCI programs are directly
applicable to understanding HIV and AIDS. These include virology, immunology,
and cell and molecular biology. In addition, the unique NCI Drug Discovery
Program has been expanded to include the AIDS Drug Discovery Program. Malignancies
complicate more than 30 percent of AIDS cases and contribute a great deal
to the morbidity and mortality of AIDS. The NCI has a special role to play
in understanding and developing interventions aimed at AIDS malignancies.
The NCI has recently funded an AIDS Malignancy Consortium that brings together
researchers, clinicians, and relevant support facilities at 13 institutions
throughout the country to foster interdisciplinary research into AIDS-associated
malignancies and to translate laboratory discoveries into new clinical interventions.
An AIDS malignancy tissue bank has been established to provide resources
for testing hypotheses about the development, progression, and response
to therapy of these cancers. New initiatives and increased funding through
the NCI's clinical trials programs throughout the country now address AIDS
malignancies. Epidemiologic and surveillance studies provide invaluable
resources for tracking HIV, AIDS and, in particular, AIDS malignancies.
The NCI Intramural Research Program has been an important, internationally
recognized center for research in HIV and in AIDS. Important discoveries
about HIV, pediatric and adult AIDS, AIDS malignancies, and AIDS therapeutics
have characterized this successful program.
The Search for New Drugs for AIDS
Successful therapeutic management of AIDS, which is caused by the human
immunodeficiency virus type 1 (HIV-1), may depend on avoiding or overcoming
resistance of the virus to drugs. While drugs may initially inhibit the
replication of HIV-1, resistance develops as a result of mutations or changes
in the genetic material of the virus. Some of these changes are in genes
that produce enzymes such as the viral reverse transcriptase (RT) and protease
that are essential for the virus to reproduce and be infectious.
Most of the HIV-1 chemotherapeutic agents used today inhibit the action
of reverse transcriptase. However, mutations in this enzyme commonly occur
during HIV-1 infection, and result in the development of drug resistance.
NCI intramural researchers, in collaboration with scientists at Rutgers
University, characterized three new HIV-1 molecular structures: structures
of two different complexes between HIV-1 RT and inhibitors and a structure
of unliganded HIV-1 RT. This new knowledge can be used to design improved
drugs that may be able to inhibit HIV-1 mutants that become resistant to
existing drugs.
NCI intramural researchers also developed a method for crystallizing
complexes of the HIV-1 virus protease with inhibitors that allows the rational
design of anti-protease drugs, and led to the discovery of several potent
new anti-HIV-1 drugs that are now in the process of being approved for human
use. Scientists have now determined the structure of the feline immunodeficiency
virus protease (FIV PR)/inhibitor complex. FIV is responsible for a disease
in domestic cats with clinical symptoms that parallel some of those observed
in human AIDS. Since the structure of FIV PR resembles other related retroviral
enzymes, knowledge about it will increase our understanding of this class
of enzymes and will allow testing of new inhibitors in a feline model before
using them in AIDS patients.
The NCI is committed to the Nation's battle against AIDS. In FY 1996 and
FY 1997, the total NCI commitment to AIDS and AIDS-related research through
all of its mechanisms is $225 million and an estimated $220 million, respectively.
AIDS research dollars are distributed throughout the budget.
Research Management and Support
Research Management and Support
includes activities essential to sustain, guide, and monitor both the extramural
and intramural activities of the NCI. These activities include overall scientific
program direction and administration by the Immediate Office of the Director,
with assistance from grant and contract science managers, finance, human
resource, legislation, science program direction and assessment, and technology
transfer staff. The review and oversight activities of both the National
Cancer Advisory Board and the President's Cancer Panel are also included.
This part of the budget also supports the NCI's share of central NIH facilities
and operations, and extramural staff salaries (intramural salaries are included
under the Intramural Research budget as is intramural facilities maintenance).
A significant portion of the NCI's information dissemination and health
education efforts are supported through this part of the budget, including
materials prepared for the general public, health and medical professionals,
and the scientific and research communities.
Other Research Support
This area incorporates smaller
grant activities such as Conference Grants, Scientific Evaluation, and Construction
grants and contracts. Conference awards support meetings, conferences, and
workshops relevant to promoting the goals of the NCI. Scientific Evaluation
awards are the vehicle that supports the scientific review of grant and
contract proposals. The grant reviews are conducted by either the NIH Division
of Research Grants or the NCI, depending on the granting mechanism. Construction
funds provide partial support for the modernization or development of cancer
research facilities at institutions located throughout the Nation. Additionally,
limited construction funds are provided for repair and improvement at the
Frederick Cancer Research and Development Center.