B.

Measurement of specific immunologic response..

to HTLV-III infection according to dose and route
of transmission in an animal model and comparison
to human response.

Study of the immune and HTLV-III antibody status
of 200 hemophilia patients who have not yet been
exposed to factor concentrates to quantify the
risk of infection among hemophilia patients.

The discovery of HTLV-III and the licensing of serologic tests to detect HTLV-III antibodies has provided additional opportunities for prevention and control. State and local health departments and many community organizations have undertaken education and counseling efforts to impart information and induce behavioral change among high risk groups. Declining rates of sexually transmitted diseases among homosexual men indicate that substantial changes are already occurring, but further change is needed as well as a greater understanding of the factors that influence change.

As part of this request we will implement a new community health education/risk reduction program throughout the Nation to provide information on AIDS to all segments of the public, particularly individuals at increased risk of AIDS, health care providers, researchers, and other groups with responsibility for persons with AIDS; implement community health education/risk reduction programs to effect behavior change; and provide medical referral and counseling programs to persons who become aware of antibody status through blood donations.

Specific activities will include:

Community Health Education/Risk Reduction

Initiation of cooperative agreements with each
of the 50 States ($75,000 to $125,000) to assist
States in appraising community needs and resources
related to the AIDS situation and to assist the
States in building their capacity to deliver health
education and risk reduction programs.

Augmentation of 15 established programs ($350,000
to $700,000) to assist those communities with

high incidence of AIDS to intensify their prevention
"'efforts and to implement evaluation mechanisms
to monitor effectiveness.

Increased involvement of CDC staff in national
strategy planning, refinement of risk reduction
guidelines, development of uniform evaluation
guidelines, technical assistance and training, and
consultation to State and local health agencies
and AIDS voluntary organizations.

Additional Resources Required

FY 1986

$14,710,000 (13 FTE)

Demonstration and Evaluation Projects

Establishment of community baseline information regarding: (1) prevalence of HTLV-III infection in groups at risk; (2) knowledge and attitudes concerning AIDS; and (3) risk-associated behavior.

Testing of appropriate interventions, including:
(1) programs to persuade individuals to remain
uninfected and prevent transmission to others

if infected; and (2) programs to counsel seropositive
and seronegative individuals.

Evaluation of interventions, including: (1) repeated
surveys to document changes in understanding AIDS
risk factors; (2) repeated surveys to evaluate
changes in behavior resulting from program efforts;
and (3) monitoring of trends in other illnesses
which are sensitive indicators of behavior changes
in high risk populations.

Development through the competitive process of
new approaches which could be more effective

in preventing and/or controlling AIDS transmission
(10 to 15 projects).

National Institutes of Health

Recent advances in the basic sciences underlying

AIDS have provided new opportunities for investigation. Observations in need of followup are being made almost on a daily basis. Activities undertaken as part of this request will capitalize on the extensive research which has been carried out since the start of the AIDS epidemic, principally epidemiologic studies to clarify the natural history of the disease and additional work toward the development of vaccines and antiviral agents. Specific activities will include:

Epidemiologic Studies

Followup studies of documented regional differences
in the prevalence of HTLV-III antibody in Kenya to
clarify the basis for low AIDS case rates in areas
endemic for HTLV-III. (NCI--$100,000)

Expansion of projects designed to pursue observations
related to the high rates of viral isolation

in seronegative sexual contacts of high-risk
group members.

(NCI--$400,000)

A study of HTLV-III transmission in seropositive,
pregnant, drug-using females and their offspring,
with followup of the children to monitor seroconversion,
immune function, and risk of AIDS. (NCI--$400,000)

Interviews with persons occupationally exposed

to HTLV-III regarding known AIDS risk factors
and details of exposures (particularly needle-stick
injuries) and serial collection of blood samples.
(NCI--$150,000)

Followup of a drug-user cohort which indicates
striking geographic difference in seropositivity
to assess changes in seroprevalence over time
and the risk of AIDS and AIDS-related illnesses.
(NCI--$350,000)

Diagnostic and Therapeutic Agents

Viral titration studies in support of clinical
trials with suramin, an antiparasitic drug, which
has been shown to have inhibitory effects on

viral reverse transcriptase at clinically achievable
levels. (NCI--$1,100,000)

has been shown to have inhibitory effects on
viral reverse transcriptase at clinically achievable
levels. (NCI--$1,100,000)

"

Screening of candidate antiviral compounds for
activity against HTLV-III with the goal of selecting
the most efficacious drugs for clinical trials.
(NIAID--$750,000; NCI--$2,000,000).

Further clinical studies with suramin and other
antiviral agents such as ribavirin and HPA23;
possibly combining such agents with immunologic
reconstitution such as bone marrow transplantation
and interleukin-2 infusion. Extrapolation of
recent advances in the treatment of cytomegalovirus
with DHPG to other immunodeficiency states.
(NIAID--$2,660,000)

Expansion of efforts to define the underlying mechanisms responsible for the altered functional properties of peripheral blood monocytes in the immunosuppression characteristic of AIDS. Monocytes

are normally the first line of host against a variety of antigens, bacteria, viruses, and tumors. (NIDR--$647,000)

Expanded work using an AIDS-virus-induced animal
model to study the pathogenesis of the disease,
particularly further development of a new serological
test which appears to accurately identify both
susceptible and immune animals.
(NINCDS--$400,000)

Vaccine Development

-

Identification and purification of antigens to
be used in HTLV-III vaccine development.
(NCI--$150,000)

Safety and antigenicity testing in humans of
candidate AIDS vaccines.

Outreach Activities

(NIAID--$1,000,000)

Development of packaged workshops on AIDS for
meetings of professional and lay organizations.
(NIAID--$320,000)

-

Three additional research project grants to evaluate
the psychological impact (i.e., stress) of testing
for HTLV-III antibody on those at high risk of
AIDS.