[Federal Register Volume 64, Number 102 (Thursday, May 27, 1999)]
[Notices]
[Pages 28822-28824]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-13493]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention
[Announcement Number 99105]


Research Studies to Characterize the Clinical Relevance of HIV 
Superinfection Notice of Availability of Funds

A. Purpose

    The Centers for Disease Control and Prevention (CDC) announces the 
availability of fiscal year (FY) 1999 funds for a cooperative agreement 
program for epidemiologic and laboratory research studies to 
characterize reinfection with Human Immunodeficiency Virus Type 1 (HIV-
1.) This program addresses the ``Healthy People 2000'' priority area of 
HIV Infection.
    The purpose of this program is to characterize the occurrence of 
reinfection with a second strain of HIV and determine whether 
reinfection has clinical relevance for the pathogenesis of HIV disease. 
Specific questions must at least include:
    1. Can naturally-occurring reinfection with a second, genotypically 
distinct strain of HIV-1 be documented after initial infection has been 
established?
    2. (How often?) Does reinfection result in the emergence of a new 
predominant strain of HIV-1?
    3. Is reinfection with a second strain of HIV-1 associated with 
clinical disease progression, emergence of resistance to antiviral 
drugs, or other adverse consequences?

B. Eligible Applicants

    Applications may be submitted by public and private nonprofit and 
for-profit organizations and by governments and their agencies; that 
is, universities, colleges, research institutions, hospitals, other 
public and private nonprofit and for-profit organizations, State and 
local governments or their bona fide agents, and federally recognized 
Indian tribal governments, Indian tribes, or Indian tribal 
organizations.
    Because studies to date suggest that reinfection with a second HIV-
1 strain may be rare or difficult to detect, a case-control study 
design may be most likely to yield expeditious answers to study 
questions. Funds under this announcement may not be used to establish a 
prospective cohort. Therefore, successful applicants must demonstrate 
access to an existing cohort for recruitment of appropriate study 
subjects for whom stored specimens are available to conduct the 
necessary retrospective analysis.

C. Availability of Funds

    Approximately $500,000 will be available in FY 1999 to fund 
approximately 2 awards. It is expected that the average new award will 
be approximately $250,000. It is expected that awards will begin on or 
about September 30, 1999. Awards will be funded for a 12-month budget 
period within a project period of up to 3 years. Funding estimates may 
vary. Continuation awards within the project period will be made on the 
basis of satisfactory progress as evidenced by required reports and the 
availability of funds.

D. Program Requirements

    In conducting activities to achieve the purpose of this program, 
the recipient will be responsible for the activities listed under 
Recipient Activities, and CDC will be responsible for conducting 
activities listed under CDC Activities.

1. Recipient Activities

    a. Develop Study Protocol: Design an appropriate study to answer 
the specific research questions related to HIV-1 reinfection.
    b. Identify Study Cohort: Identify a cohort of HIV-infected persons 
from which eligible study subjects can be recruited, for whom (1) 
sufficient information is available to document a known or likely re-
exposure to a second strain of HIV-1; (2) a clinically significant 
event such as disease progression or emergence of antiviral drug 
resistance has been recognized; and (3) suitable stored specimens are 
available for genotypic analysis of viral strains of HIV-1 before and 
after occurrence of the clinical event.
    c. Conduct Productive and Scientifically Sound Studies: Identify, 
recruit, obtain informed consent, and enroll study participants as 
determined by the study protocol and the program requirements. Perform 
the laboratory tests necessary to characterize viral strains as 
determined by the study protocol. Ideally, recipients would be able to 
characterize the HIV-1 strain in the source partner epidemiologically 
associated with reinfection.
    d. Publish the Results of the Study: Upon completion, publish the 
results of the study. At the completion of the funding period, 
recipients should optimally prepare at least one manuscript based on 
the funded research for a peer-reviewed journal. All recipients will 
provide copies of relevant publications and other significant documents 
to CDC project co-investigators, and any other local agencies or 
individuals with a special interest in the research project.
    e. Share Data and Specimens: Share data and specimens (when 
appropriate) with other collaborators to answer the project's specific 
research questions.

2. CDC Activities

    a. Assist in Protocol Development: CDC staff will assist in the 
development

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of a research protocol for Institutional Review Board (IRB) review by 
all cooperating institutions participating in the research project. The 
CDC IRB will review and approve the protocol initially and on at least 
an annual basis until the research project is completed.
    b. Provide Technical Assistance: CDC staff will assist in the 
design of the research and quality assurance of laboratory methods.
    c. Provide Scientific Expertise: CDC staff will provide current 
scientific and programmatic information relevant to the studies, and 
will provide technical advice throughout the study, including study 
design, data analysis and publication.
    d. Share Data and Specimens: CDC staff will assist in the 
dissemination of study results and distribution of specimens.

E. Application Content

    Use the information in the Program Requirements, Other 
Requirements, and Evaluation Criteria sections to develop the 
application content. Your application will be evaluated on the criteria 
listed, so it is important to follow them in laying out your program 
plan. Applications must not be more than 25 double-spaced pages, 
printed on one side, with one inch margins and 12 point font (exclusive 
of official PHS application pages and relevant attachments.) 
Applications will not be reviewed if the narrative is more than 25 
pages, not counting PHS forms and appendices. In the narrative, address 
the following:
    1. Background: Briefly describe your research questions.
    2. Study design: Describe: (a) the proposed study design and (b) 
how this study design will address the specific research questions.
    3. Study cohort: Describe: (a) the study cohort from which eligible 
study subjects will be recruited; (b) how this study cohort was 
selected; (c) specific clinical and epidemiologic information available 
for potential study subjects related to the study objectives; and (d) 
the availability, quality, and condition of stored specimens necessary 
for the laboratory analysis as determined by the study design. Also 
provide evidence that the necessary information and specimens from this 
cohort will be accessible for the purposes of this study.
    4. Laboratory methods: Describe the laboratory methods that will be 
used to characterize the viral strains, and provide evidence that these 
are adequate to distinguish between different strains of HIV-1 with the 
same envelope subtype.
    5. Organization: Describe: (a) the existing relationship between 
the proposed study staff, managers of the proposed study cohort, and 
the laboratory which will perform the study analyses; (b) the proposed 
organization structure, with lines of authority, for implementing the 
proposed study; (c) the current working relationship with any research, 
academic, scientific groups, community-based organizations or other 
affiliated organizations; and (d) strategy for identification and 
recruitment of study participants.
    6. Capacities: Describe your capacity and experience in: (a) 
performing previous clinical or laboratory research involving the 
recruitment of HIV-positive persons and collection of clinical or 
epidemiologic data; (b) performing genotypic analysis of viral strains 
of HIV-1; (c) ensuring the hiring of staff for implementing the study 
in a timely manner; and (d) participating in collaborative research 
with other research organizations.
    7. Personnel: Describe (a) personnel proposed for implementing the 
research study; (b) roles and responsibilities for each proposed staff; 
and (c) evidence of qualifications for the responsibilities proposed.
    8. Budget and Line-Item Justification: Provide an annualized budget 
that anticipates the organizational and operational needs to carry out 
the proposed study.

F. Submission and Deadline

    Submit the original and five copies of PHS-398 (OMB Number 0925-
0001) (adhere to the instructions on the Errata Instruction Sheet for 
PHS 398). Forms are in the application kit. On or before August 1, 1999 
submit the application to: Kevin Moore, Grants Management Specialist, 
Grants Management Branch, Procurement and Grants Office, Centers for 
Disease Control and Prevention (CDC), 2920 Brandywine Road, Room 3000, 
Mail Stop E-15, Atlanta, GA 30341, Email KGM[email protected].
    Deadline: Applications shall be considered as meeting the deadline 
if they are either received on or before the stated deadline date or 
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 are not acceptable proof of timely mailing. Applications that 
do not meet these criteria are considered late applications, will not 
be considered, and will be returned to the applicant.

G. Evaluation Criteria

    Each application will be evaluated individually based on the 
evidence submitted against the following criteria by an independent 
review group appointed by CDC (Note: total possible point value is 
110):
    1. Demonstration of the applicant's understanding of the research 
objectives and the ability, willingness, and need to collaborate in the 
study design and analysis, and (when appropriate) sharing of data and 
specimens. Evidence should include a brief review of previous studies 
related to HIV-1 infection, and laboratory methods for characterizing 
viral strains of HIV-1. (15 points)
    2. Quality of an explicit research plan adequate to address the 
study questions. The research plan should include a specific study 
design (e.g., case series, case-control analysis) and describe how HIV-
infected study subjects will be identified and how their re-exposure to 
infection with another strain of HIV-1 will be documented. The research 
plan should specify the anticipated number of subjects, and demonstrate 
how this study design and subject selection will resolve the study 
questions. Preference will be given to applicants who propose to 
evaluate reinfection in persons whose initial infection and possible 
reinfection are both due to group M, subtype B strains of HIV-1. (25 
points)
    3.a. Capacity to access a cohort of HIV-infected persons with 
sufficient epidemiologic information to document re-exposure to HIV-1, 
adequate descriptive clinical information to identify significant 
clinical events such as disease progression or emergence of antiviral 
drug resistance, and the availability of adequate stored specimens to 
implement the study. (15 points)
    b. The degree to which the applicant has met the CDC policy 
requirements regarding the inclusion of women, ethnic, and racial 
groups in the proposed research. This includes:
    (1) The proposed plan for the inclusion of both sexes and racial 
and ethnic minority populations for appropriate representation.
    (2) The proposed justification when representation is limited or 
absent.
    (3) A statement as to whether the design of the study is adequate 
to measure differences when warranted.
    (4) A statement as to whether the plans for recruitment and 
outreach for study participants include the process of establishing 
partnerships with communities and recognition of mutual benefits. (5 
points)
    4. Capability to employ laboratory methods sufficient to 
differentiate

[[Page 28824]]

among viral strains of HIV-1 with the same envelope subtype. Evidence 
should include a justification for the laboratory techniques selected, 
documentation of either proficiency with these methods or specific 
plans and commitments to access services from a laboratory which has 
demonstrated this proficiency, and assurance that capacity is adequate 
to accomplish the analyses necessary for the proposed research. Letters 
of support from collaborating institutions or organizations should be 
included. (15 points)
    5. Demonstration of a history of conducting comparable research 
studies. Research studies related to the molecular biology, genetic 
diversity, or genetic evolution of HIV-1 are of greatest interest. (10 
points)
    6. The capacity to effectively manage the study as evidenced by the 
proposed organizational structure, the quality and experience of 
proposed personnel with realistic and sufficient percentage-time 
commitments; clarity of the described duties and responsibilities of 
project personnel; adequacy of the facilities; and plans for 
administration of the project including project oversight and data 
management. Evidence should document qualifications of a prospective PI 
and other key personnel, and, if indicated, support arrangements with a 
university, community-based or other affiliated organization, etc. (15 
points)
    7. A comprehensive schedule, including a time line, for 
accomplishing the activities of the research and an evaluation plan 
that identifies methods and instruments for evaluating progress in 
designing and implementing the research objectives. (10 points)
    8. Other (Not Scored).
    a. Budget: The budget will be reviewed to determine the extent to 
which it is reasonable, clearly justified, consistent with the intended 
use of funds, and allowable. All budget categories should be itemized.
    b. Human Subjects: Whether or not exempt from the Department of 
Health and Human Services (DHHS) regulations, are procedures adequate 
for the protection of human subjects?

H. Other Requirements

Technical Reporting Requirements

    Provide CDC with original plus two copies of
    1. Annual progress reports;
    2. Financial status report, no more than 90 days after the end of 
the budget period; and
    3. Final financial status and performance reports, no more than 90 
days after the end of the project period. Send all reports to the 
Grants Management Specialist identified in the paragraph Where to 
Obtain Additional Information.
    The following additional requirements are applicable to this 
program. For a complete description of each, see Attachment I in the 
application kit.

AR-1  Human Subjects Requirements
AR-2  Requirements for Inclusion of Women and Racial and Ethnic 
Minorities in Research
AR-4  HIV/AIDS Confidentiality Provisions
AR-6  Patient Care
AR-7  Executive Order 12372 Review
AR-9  Paperwork Reduction Act Requirements
AR-10  Smoke-Free Workplace Requirements
AR-11  Healthy People 2000

I. Authority and Catalog of Federal Domestic Assistance Number

    This program is authorized under Sections 301 and 311 of the Public 
Health Service Act, [42 U.S.C. 241 and 243], as amended. The Catalog of 
Federal Domestic Assistance number is 93.943.

J. Where To Obtain Additional Information

    To receive additional written information and to request an 
application kit, call 1-888-GRANTS4 (1-888-472-6874). You will be asked 
to leave your name and address and to identify the Announcement number, 
99105. If you have questions after reviewing the contents of all the 
documents, business management technical assistance may be obtained 
from: Kevin Moore, Grants Management Specialist, Grants Management 
Branch, Procurement and Grants Office, Centers for Disease Control and 
Prevention (CDC), 2920 Brandywine Road, Room 3000, Mail Stop E-15, 
Atlanta, GA 30341, Telephone (770) 488-2737, E-mail address 
KGM[email protected].
    For a detailed description of the additional requirements in 
Attachment 1, to download forms required by this announcement, and to 
review other CDC program announcements, see the CDC home page on the 
Internet: www.cdc.gov.
    For program technical assistance, contact Kay Lawton, Division of 
HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, 
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, 
NE., Mail Stop E-46, Atlanta, Georgia 30333, telephone (404) 639-6131, 
E-mail address KEL[email protected].

    Dated: May 21, 1999.
John L. Williams,
Director, Procurement and Grants Office, Centers for Disease Control 
and Prevention (CDC).
[FR Doc. 99-13493 Filed 5-26-99; 8:45 am]
BILLING CODE 4163-18-P