FY 1997; Studies To Evaluate the Epidemiologic and Laboratory Characteristics of Human Immunodeficiency Virus (HIV) Infection Among United States Blood and Plasma Donors

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Announcement Number 797]

FY 1997; Studies To Evaluate the Epidemiologic and Laboratory

Characteristics of Human Immunodeficiency Virus (HIV) Infection Among

United States Blood and Plasma Donors

Introduction

The Centers for Disease Control and Prevention (CDC) announces the

availability of fiscal year (FY) 1997 funds for cooperative agreements

to provide assistance for epidemiologic surveillance studies of human

immunodeficiency virus (HIV) in U.S. blood and plasma donors. These

studies will be conducted to describe the epidemiology of human

immunodeficiency virus (HIV), other retroviruses, and related

conditions in persons whose blood tests positive for HIV antibody, HIV

antigen, or other related laboratory markers. Additional funds will be

available for laboratory studies of the genetic variation of HIV among

blood and plasma donors and other selected populations.

CDC is committed to achieving the health promotion and disease

prevention objectives of ``Healthy People 2000,'' a national activity

to reduce morbidity and mortality and improve the quality of life. This

announcement is related to the priority area of HIV Infection. (For

ordering a copy of ``Healthy People 2000,'' see the Section WHERE TO

OBTAIN ADDITIONAL INFORMATION.)

Authority

This program is authorized under Sections 301(a) and 317(k)(2) of

the Public Health Service Act (42 U.S.C. 241(a) and 247b(k)(2)), as

amended. Applicable program regulations are set forth in 42 CFR Part

52, entitled ``Grants for Research Projects.''

Smoke-Free Workplace

CDC strongly encourages all cooperative agreement recipients to

provide a smoke-free workplace and promote the non-use of all tobacco

products. Public Law 103-227, the Pro-Children Act of 1994, prohibits

smoking in certain facilities that receive Federal funds in which

education, library, day care, health care, and early childhood

development services are provided to children.

Eligible Applicants

Eligible applicants include all nonprofit and for-profit blood

centers and organizations and governments and their agencies. Thus,

universities, colleges, research institutions, hospitals, and other

public and private organizations, State and local health departments or

their bona fide agents or instrumentalities, federally recognized

Indian tribal governments, Indian tribes or Indian tribal

organizations, and small, minority- or women-owned businesses are

eligible to apply.

Note: Organizations described in section 501(c)(4) of the

Internal Revenue Code of 1986 that engage in lobbying are not

eligible to receive Federal grant/cooperative agreement funds.

Availability of Funds

Approximately $1,200,000 will be available in FY 1997 to fund

approximately 5-10 awards. It is expected that the average award will

be approximately $200,000, with a range from $20,000 to $800,000. It is

expected that approximately 2 new and 6 competing renewal awards will

be made and that awards will begin on or about September 30, 1997.

Awards will be funded for a 12-month budget period within a project

period of up to 5 years. Funding estimates may vary and are subject to

change.

Continuation awards within the project period will be made on the

basis of satisfactory programmatic progress and the availability of

funds.

Use of Funds

Restrictions on Lobbying

Applicants should be aware of restrictions on the use of Department

of Health and Human Services (HHS) funds for lobbying of Federal or

State legislative bodies. Under the provisions of 31 U.S.C. Section

1352 (which has been in effect since December 23, 1989), recipients

(and their subtier contractors) are prohibited from using appropriated

Federal funds (other than profits from a Federal contract) for lobbying

Congress or any Federal agency in connection with the award of a

particular contract, grant, cooperative agreement, or loan. This

includes grants/cooperative agreements that, in whole or in part,

involve conferences for which Federal funds cannot be used directly or

indirectly to encourage participants to lobby or to instruct

participants on how to lobby.

In addition, the FY 1997 Departments of Labor, HHS, and Education,

and Related Agencies Appropriations Act, which became effective October

1, 1996, expressly prohibits the use of 1997

[[Page 37059]]

appropriated funds for indirect or ``grass roots'' lobbying efforts

that are designed to support or defeat legislation pending before State

legislatures. Section 503 of this new law, as enacted by the Omnibus

Consolidated Appropriations Act, 1997, Division A, Title I, Section

101(e), Public Law No. 104-208 (September 30, 1996), provides as

follows:

Sec. 503(a) No part of any appropriation contained in this Act

shall be used, other than for normal and recognized executive-

legislative relationships, for publicity or propaganda purposes, for

the preparation, distribution, or use of any kit, pamphlet, booklet,

publication, radio, television, or video presentation designed to

support or defeat legislation pending before the Congress, * * *

except in presentation to the Congress or any State legislative body

itself.

(b) No part of any appropriation contained in this Act shall be

used to pay the salary or expenses of any grant or contract

recipient, or agent acting for such recipient, related to any

activity designed to influence legislation or appropriations pending

before the Congress or any State legislature.

Background

In the United States, about 8 million people donate approximately

14 million units of whole blood each year; donors also give about 12

million units of plasma for use in making immune globulin, clotting

factors, and other products. During the last decade, improved donor

screening and education and better laboratory tests for blood-borne

viruses have markedly increased the safety of the nation's blood

supply.

The Centers for Disease Control and Prevention has monitored data

from the routine testing of blood donors since the first HIV antibody

screening test was licensed in 1985. Since 1988, CDC has collaborated

with the National American Red Cross and other major blood collection

agencies to systematically evaluate the characteristics of HIV-infected

donors through detailed interviews and follow-up. From 1988 to 1995,

the seroprevalence of HIV among blood donors decreased threefold, from

approximately 1 in 4,000 to 1 in 12,000 donors. This decrease was due

in part to the elimination of seropositive donors from the repeat donor

pool. However, HIV seroprevalence among first-time donors has also

declined. Because persons with known risks for HIV infection are

actively discouraged from donating, information about HIV-infected

donors identified during the screening process is valuable for further

improving donor deferral procedures and may offer clues to emerging

patterns of HIV transmission.

Current estimates of the residual risk of HIV transmission from

blood transfusion are based on mathematical models; these models

require estimates of the incidence of HIV infection among blood donors

and the length of the infectious window period. A recent analysis

suggested that there was a risk of 1 case of HIV transmission for every

450,000 to 660,000 donations of screened blood. This estimate is much

smaller than earlier estimates, principally because of the improved

sensitivity of enzyme immunoassay screening tests for HIV antibody. The

ability to monitor the risk of HIV transmission by blood transfusion

depends on methods for maintaining surveillance of incident HIV

infection among blood donors and characterizing the infectious window

period.

Since March 1996, donated blood has also been screened for HIV p24

antigen. On average, p24 antigen tests become positive approximately 6

days before enzyme immunoassays for HIV antibody. Surveillance

conducted by CDC, the National American Red Cross, and other blood

collection agencies suggest that p24 antigen screening has thus far

done little to improve blood safety; however, it has raised issues

concerning counseling and exclusion of donors who have false positive

test results and donors who may seek testing by a more sensitive test

than is routinely offered. In addition, concerns have been raised over

the presence of HIV strains poorly detected by commonly used screening

assays (e.g., group O). As testing technology continues to evolve,

blood donation provides a critical setting for evaluating the

performance characteristics of existing and new screening techniques,

as well as their potential impact on blood safety.

Although incidence and prevalence of HIV infection are lower among

blood donors than among unselected populations, the routine screening

of very large numbers of repeat blood donors identifies substantial

numbers of persons with recently acquired HIV infection. A newly

developed, ``detuned'' enzyme immunoassay can identify HIV infections

acquired during a relatively recent interval among first-time, as well

as repeat, donors and among other significant populations. Defining the

epidemiologic and laboratory characteristics of these recently infected

persons is important for understanding the evolution of the HIV

epidemic in the U.S. For example, HIV genomes from such persons are

needed for larger studies of subtype variation and primary drug

resistance.

Purpose

The purpose of these awards is to support research for

epidemiologic surveillance studies to gain a greater understanding of

the HIV epidemic and the safety of the U.S. blood supply. In

particular, studies with flexibility to support surveillance of other

transfusion-transmissible agents in addition to HIV will be considered.

I. Surveillance and Interview Studies of Blood and Plasma Donor

Populations

A. Monitor the prevalence and incidence of HIV infection in blood

and plasma donors at selected centers throughout the U.S. and Puerto

Rico.

B. Analyze the demographic, behavioral, and laboratory

characteristics of HIV-infected and non-infected donors to strengthen

the effectiveness of donor screening and deferral processes.

C. Estimate the risk of HIV transmission from screened blood and

plasma.

D. Identify persons and characteristics of persons recently

infected with HIV.

II. Laboratory Studies of Blood and Plasma Donors and Other Significant

Populations

A. Evaluate the effectiveness of screening blood donations for HIV-

1 p24 antigen.

B. Evaluate the performance of proposed or potential HIV screening

tests (e.g., amp-RT and viral RNA assays).

C. Describe the evolution of laboratory markers during the interval

between acquisition of HIV infection and seroconversion (including the

``window period'').

D. Conduct molecular epidemiologic studies of HIV and related

viruses in blood and plasma donors and other populations of

epidemiologic significance. These studies could include surveillance

for non-B HIV subtypes, primary antiretroviral drug resistance, and

segregation of viral strains according to demographic and behavioral

risk characteristics.

Applications should indicate whether they are addressing research

issues identified under sections I. or II. above, or both. Applications

for sections I. and II. will be evaluated separately.

Program Requirements

In conducting activities to achieve the purpose of this program,

the recipient shall be responsible for the activities listed under A.

(Recipient Activities), and CDC shall be responsible for conducting

activities listed under B. (CDC Activities). The applications should be

presented in a manner that

[[Page 37060]]

demonstrates the applicant's ability to address the proposed activities

in a collaborative manner with CDC.

A. Recipient Activities

1. Develop research study protocols, consent forms, questionnaires,

and data collection methods.

2. Identify, recruit, obtain informed consent from, and enroll an

adequate number of study participants as determined by study protocols

and program requirements.

3. Conduct epidemiologic studies at specified sites using approved

study protocols established through the recipient's participation with

CDC and other collaborating institutions.

4. Perform selected laboratory tests according to established

research protocols. Store all HIV seropositive sera and additional

specimens (sera or cells) as may be required by the research study

designs.

5. Participate in the development and maintenance of data

management systems for the study.

6. Share data and specimens with other collaborators when

appropriate to answer specific research questions.

7. Analyze study data and present findings in scientific

presentations and publications.

B. CDC Activities

1. Provide technical assistance in the design and conduct of the

research.

2. Provide technical guidance in the development of study

protocols, consent forms and questionnaires, including training and

pretesting as necessary.

3. Assist in designing a data management system. As requested,

carry out central data management functions.

4. As requested, perform selected laboratory tests.

5. Provide specimens for selected laboratory studies.

6. Facilitate collaboration among the different sites including

laboratories and consultants.

7. Collaborate with recipients in the analysis of research

information and the presentation of research findings.

Technical Reporting Requirements

1. An original and two copies of annual progress reports are

required no later than 90 days after the end of the budget period. The

annual reports for current awardees will be submitted with the renewal

application.

2. Final financial status and performance report is also required

no later than 90 days after the end of the project period. All reports

are submitted to the Grants Management Branch, Procurement and Grants

Office, CDC.

Application Content

Applications must be developed in accordance with PHS Form 5161-1

and the instructions outlined under the following section headings. The

application should provide a detailed description of first-year

activities and only briefly describe future-year activities. To assist

in evaluating the application, please limit the number of pages to 25

plus attachments.

A. Executive Summary

B. Table of Contents

C. Background and Needs

1. Demographic and geographic characteristics of the proposed study

population.

2. Reported cases of AIDS and/or HIV infection, patterns of

behavioral risk correlated illnesses (e.g., syphilis, hepatitis, etc.)

in the study population.

3. Previous efforts to conduct similar studies and uses of the

resulting data.

D. Capacity

1. Demonstrated knowledge, ability and resources to conduct

epidemiologic or laboratory studies.

2. Ability to enroll and evaluate adequate numbers of eligible

study participants or to obtain and examine appropriate numbers and

types of laboratory specimens.

3. Position descriptions for all key project personnel. These may

be included in the appendix but should be referenced in the text.

E. Goals and Objectives

1. List one or more goals for the project.

2. List specific measurable outcome objectives related to program

development and implementation; training and data quality; data

analysis and dissemination, including potential plans for linkage with

other data systems; and program evaluation.

F. Methods/Activities

1. Describe activities related to each objective.

2. Specify timelines for completing each activity.

3. Designate personnel resources and assignments to specific

project activities.

G. Project Evaluation

1. Evaluation plan should contain specific activities to collect

data to measure program development and implementation.

2. Describe how information will be obtained, prepared in specific

reports, and used to improve the program.

H. Budget

1. Line-item descriptive justification for personnel, travel,

supplies and other services should be submitted. Applicant should be

precise about the purpose of each budget item as it relates to the

project.

2. If applicable, applicants requesting funding for contracts

should include the name of the person or firm to receive the contract,

the method of selection, the period of performance, and a description

of the contracted service requested.

3. Funding levels for years two and through five should be

estimated.

I. Supporting Materials

1. Curriculum vitae and job descriptions of critical staff.

2. Letters of endorsement and/or collaboration of participating

centers, agencies and/or State or local public health departments.

Evaluation Criteria

Applications will be reviewed and evaluated according to the

following criteria:

1. The applicant demonstrates the knowledge, ability and resources

to conduct epidemiologic or laboratory studies of HIV and related

viruses in U.S. blood and plasma donors or other populations of

epidemiologic significance. (30 points)

2. The applicant demonstrates the ability to enroll and evaluate

adequate numbers of eligible study participants (e.g., HIV-seropositive

donors) or to obtain and examine appropriate numbers and types of

laboratory specimens. (25 points)

3. The applicant presents a sound plan for conducting and

evaluating program activities. If tests of clinical significance are

performed, the application should include a plan for notifying study

subjects. (15 points)

4. The applicant proposes objectives that are measurable, specific,

time-phased, and related to required recipient activities and program

purpose. (10 points).

5. The applicant demonstrates willingness to cooperate in a study

with CDC and other collaborating institutions. (10 points)

6. The size, qualifications, and time allocation of the proposed

staff and the availability of facilities are adequate for the study.

(10 points)

7. The budget is reasonable, clearly justified, consistent with the

intended use of funds, and allowable. All budget categories should be

itemized. (Not scored)

8. Procedures are adequate for the protection of human subjects,

whether

[[Page 37061]]

or not exempt from the Department of Health and Human Services (DHHS)

regulations. (Not scored) Recommendations on the adequacy of

protections include: (a) Protections appear adequate and there are no

comments to make or concerns to raise; (b) protections appear adequate,

but there are comments regarding the protocol; (c) protections appear

inadequate and the Objective Review Group (ORG) has concerns related to

human subjects; or (d) disapproval of the application is recommended

because the research risks are sufficiently serious and protection

against the risks are inadequate as to make the entire application

unacceptable.

Funding Priority

Priority will be given to competing continuation applications from

satisfactorily performing projects over applications for projects not

already receiving support under the program. Projects will be awarded

so that the composite of projects reflects the geographic and

demographic distribution of the study population.

Executive Order 12372 Review

Applications are not subject to review under Executive Order 12372,

Intergovernmental Review of Federal Programs.

Public Health System Reporting Requirements

This program is not subject to the Public Health System Reporting

Requirements.

Catalog of Federal Domestic Assistance Number

The Catalog of Federal Domestic Assistance number is 93.944, Human

Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Virus Syndrome

(AIDS) Surveillance.

Other Requirements

1. Paperwork Reduction Act

Projects that involve the collection of information from 10 or more

individuals and funded by cooperative agreement will be subject to

review by the Office of Management and Budget (OMB) under the Paperwork

Reduction Act.

2. Human Subjects

This program involves research on human subjects. Therefore, all

applicants must comply with the Department of Health and Human Services

Regulations, 45 CFR part 46, regarding the protection of human

subjects. Assurance must be provided to demonstrate that the project or

activity will be subject to initial and continuing review by an

appropriate institutional review committee. The applicant will be

responsible for providing assurance in accordance with the appropriate

guidelines and form provided in the application kit.

In addition to other applicable committees, Indian Health Service

(IHS) institutional review committees also must review the project if

any component of IHS will be involved with or support the research. If

any American Indian community is involved, its tribal government must

also approve that portion of the project applicable to it.

3. HIV Program Review Panel

Recipients must comply with the document entitled Content of AIDS-

Related Written Materials, Pictorials, Audiovisuals, Questionnaires,

Survey Instruments, and Educational Sessions (June 1992) (a copy is in

the application kit). To meet the requirements for a program review

panel, recipients are encouraged to use an existing program review

panel, such as the one created by the State health department's HIV/

AIDS prevention program. If the recipient forms its own program review

panel, at least one member must be an employee (or a designated

representative) of a State or local health department. The names of the

review panel members must be listed on the Assurance of Compliance form

CDC 0.1113, which is also included in the application kit. The

recipient must submit the program review panel's report that indicates

all materials have been reviewed and approved.

4. Patient Care

Applicants should provide assurance that all HIV-infected patients

enrolled in their studies will be linked to an appropriate local HIV

care system that can address their specific needs such as medical care,

counseling, social services, and therapy. Details of the HIV care

system should be provided, describing how patients will be linked to

the system. Funds will not be made available to support the provision

of direct care for study participants.

5. Women, Racial and Ethnic Minorities

It is the policy of the CDC to ensure that individuals of both

sexes and the various racial and ethnic groups will be included in CDC-

supported research projects involving human subjects, whenever feasible

and appropriate. Racial and ethnic groups are those defined in OMB

Directive No. 15 and include American Indian, Alaskan Native, Asian,

Pacific Islander, Black and Hispanic. Applicants shall ensure that

women, racial and ethnic minority populations are appropriately

represented in applications for research involving human subjects.

Where clear and compelling rationale exist that inclusion is

inappropriate or not feasible, this situation must be explained as part

of the application. This policy does not apply to research studies when

the investigator cannot control the race, ethnicity and/or sex of

subjects. Further guidance to this policy is contained in the Federal

Register, Vol. 60, No. 179, Friday, September 15, 1995, pages 47947-

47951 (a copy is included in the application kit).

6. Confidentiality

Recipients must describe confidentiality and security provisions to

protect data collected through HIV/AIDS surveillance, including copies

of local data release policies; employee training in confidentiality

provisions; State laws, rules, or regulations pertaining to the

protection or release of surveillance information; and physical

security of hard copies and electronic files containing confidential

surveillance information. Recipients must describe any laws, rules,

regulations, or health department policies that require or permit the

release of patient identifying information collected under the HIV/AIDS

surveillance system to entities outside of the public health department

and measures the health department has taken to ensure that the

confidentiality of individuals reported to the surveillance system is

protected from further or unlawful disclosure.

Application Submission and Deadline

The original and two copies of the application PHS Form 5161-1 (OMB

Number 0937-0189) must be submitted to Van Malone, Grants Management

Officer, Grants Management Branch, Procurement and Grants Office,

Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry

Road, NE., Room 300, Mail Stop E-15, Atlanta, Georgia 30305 on or

before August 11, 1997.

1. Deadline

Applications shall be considered as meeting the deadline if they

are either:

A. Received on or before the stated deadline date; or

B. Sent on or before the deadline date and received in time for

submission to the independent review group. (Applicants must request a

legibly dated U.S. Postal Service postmark or obtain a legibly dated

receipt from a commercial carrier or U.S. Postal Service. Private

metered postmarks shall

[[Page 37062]]

not be accepted as proof of timely mailing.)

2. Late Applications

Applications that do not meet the criteria in 1.A. or 1.B. above

are considered late applications. Late applications will not be

considered in the current competition and will be returned to the

applicant.

Where To Obtain Additional Information

A complete program description, information on application

procedures, an application package, and business management technical

assistance may be obtained from Van Malone, Grants Management Officer,

Grants Management Branch, Procurement and Grants Office, Centers for

Disease Control and Prevention (CDC), 255 East Paces Ferry Road, NE.,

Room 300, Mail Stop E-15, Atlanta, Georgia 30305, telephone (404) 842-

6575, Email address [email protected]. The announcement will be available on

one of two Internet sites on the publication date: CDC's home page at

http://www.cdc.gov, or at the Government Printing Office home page

(including free access to the Federal Register) at http://

www.access.gpo.gov.

Programmatic technical assistance may be obtained from Dr. Richard

Steketee or Dr. Marta Gwinn, Division of HIV/AIDS Prevention, National

Center for HIV, STD, TB Prevention, Centers for Disease Control and

Prevention (CDC), 1600 Clifton Road, NE., Mail Stop E-46, Atlanta,

Georgia 30333, telephone (404) 639-2090. Eligible applicants are

encouraged to call before developing and submitting their application.

Please refer to Announcement Number 797 when requesting information.

Potential applicants may obtain a copy of ``Healthy People 2000''

(Full Report: Stock No. 017-001-00474-0) or ``Healthy People 2000''

(Summary Report: Stock No. 017-001-00473-1) referenced in the

Introduction from the Superintendent of Documents, Government Printing

Office, Washington, DC 20402-9325, telephone (202) 512-1800.

Dated: July 3, 1997.

Joseph R. Carter,

Acting Associate Director for Management and Operations, Centers for

Disease Control and Prevention (CDC).

[FR Doc. 97-18062 Filed 7-9-97; 8:45 am]

BILLING CODE 4163-18-P