and Human Services (HHS)
EXPIRED
TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) IN SEMEN
RELEASE DATE: May 1, 2003
PA NUMBER: PA-03-116
March 2, 2006 (NOT-OD-06-046) Effective with the June 1, 2006 submission date,
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. Accordingly, this funding opportunity
expires on the date indicated below. Replacement R01 (PA-06-165) and R21 (PA-06-166)
funding opportunity announcements have been issued for the submission date
of June 1, 2006 and submission dates thereafter.
See NOT-OD-06-048 for information on May 1, 2006 Submission Date for AIDS and
AIDS-related R03 and R21 Applications.
EXPIRATION DATE: March 2, 2006
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov)
National Institute of Child Health and Human Development (NICHD)
(http://www.nichd.nih.gov)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER (S):
93.849, 93.864
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
through its Division of Kidney, Urologic and Hematologic Diseases (DKUHD) and
the National Institute of Child Health and Human Development, Center for
Population Research invite investigators to submit research grant
applications which will increase the basic and clinical knowledge of the
biology of HIV in semen. Direct exposure to semen of HIV seropositive men is
a major route for transmission of HIV type I. This announcement focuses on
studies that will elucidate the factors that determine HIV shedding in the
male genital tract. This includes studies that elucidate the infectivity of
HIV in semen fractions, the effect of antiretroviral therapy on HIV
infectivity in semen fractions, the relationship between the immunobiology of
the male genital tract and HIV replication and infectivity, and factors such
as genital tract inflammation which influence HIV transmission through semen.
Of particular interest are studies of the anatomic sites of virus infected
cells and virus production in the male genital tract. The intent of this
Program Announcement (PA) is to encourage investigator-initiated research, to
attract new investigators to the field, and to increase interdisciplinary
research to enhance the scope and effectiveness of research in this area.
RESEARCH OBJECTIVES
Background
The transmission of HIV in semen is one the major factors in the progression
of the AIDS epidemic. Sources of HIV transmission in semen fluid have been
identified as both the free virus particles and infected cells. Semen is a
complex mixture of seminal fluid (semen) sperm, and cells which contain many
and variable enzymes, proteins, growth factors, minerals, and carbohydrates
which originate from the accessory sexual organs of the male genital tract
(testes, epididymides, seminal vesicles, prostate and Cowper's glands).
Similarly the pH, osmolality and other factors of semen also vary with
location, site of origin, as well as other systemic factors of the host. The
testes, epididymides, seminal vesicles, prostate, and the glands and cells of
the urethra have all been implicated as potential reservoirs and sites of
replication for HIV.
Confounding factors in the study of the biology of HIV in semen are the
limited knowledge of the relationship between systemic host factors, the
immunology of the male urogenital tract, and levels of potentially infectious
HIV in the semen. The anatomical origins and sources of HIV in the male
genital tract have not been positively identified; neither have the effects
of therapeutic interventions, specifically antiviral therapies, on HIV
infectivity and transmission.
The lack of any information about the mechanisms of viral clearance from the
semen is a significant impediment to research progress. In contrast, the
kinetics of clearance of the HIV from blood, e.g. at the onset of antiviral
therapy, have been well described and are shown to be very rapid (i.e. within
hours) suggesting that there are major clearance mechanisms via the kidney
(and possibly the liver).
Scientific Objectives
Identify and characterize the anatomic source(s) of and the reservoirs of HIV
and the HIV infected cells in semen.
Identify sources of HIV infection and replication in the male genital tract
and accessory sex organs.
Identify and characterize immune privileged and other reservoirs of HIV
production in the male genital tract.
Develop methods that accurately characterize the relationship between serum
HIV levels and infectivity of HIV in semen.
Describe semen factors and constituents that affect HIV infectivity,
including endogenous anti-viral and immunomodulatory properties of semen
Characterize the effect of antiretroviral and other forms of HIV therapy,
including immunotherapy and vaccine therapy, on HIV in semen and in male
genital organs and tissues.
Develop novel approaches to the eradication of HIV from semen.
Elucidate the mechanisms of transmission of HIV in semen through the mucous
membranes of the sexual partner.
Compare clearance rates and mechanisms of HIV in semen and blood after
antiviral therapy.
Determine if HIV in semen is genetically and/or biologically distinct from
the HIV in blood.
Examine the relationship between genital co-infections, including
prostatitis, and their treatment on HIV transmissibility
Develop ex-vivo models to study HIV transmission in the male genital tract
Examine the effect of circumcision and genital hygiene on HIV/STD
transmission
Examine the effect of hormonal supplementation on the viral load and
transmissibility in the male genital tract.
Examine the contribution of viral genotype and phenotype to HIV transmission
Program Objectives
Increase the diversity of scientific expertise applied to basic and clinical
research studies related to the pathobiology of HIV transmission in semen.
Involve and integrate new investigators in research studies related to HIV,
semen and the biology of the male genital tract.
Involve and integrate experienced investigators from diverse basic and
clinical research areas in research on semen, the male genital tract, and HIV
transmission.
Develop and increase collaborative research efforts focusing on HIV
transmission in semen between clinicians and basic scientists
MECHANISM(S) OF SUPPORT
This PA will use the NIH R01 and R21 award mechanisms. As an applicant, you
will be solely responsible for planning, directing, and executing the
proposed project. The total requested project period for an application
submitted in response to this PA may not exceed five years for the R01, and
two years for the R21.
The R21 award (see http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html)
is an exploratory/developmental research grant for support of
high-risk pilot and feasibility research designed to develop new ideas
sufficiently to allow future submission of a full R01 application. For R21
application, you may request a project period of up to two years with a
combined budget for direct costs of up $275,000 for the two year period. For
example, you may request $100,000 in the first year and $175,000 in the second
year. The request should be tailored to the needs of your project. Normally,
no more than $200,000 may be requested in any single year. Competing
continuation applications will not be accepted. Two revisions of a
previously reviewed exploratory/developmental grant application may be
submitted as defined in NIH Policy at
http://grants.nih.gov/grants/policy/amendedapps.htm.
Applicants are encouraged to contact program staff for information about
choosing the appropriate grant mechanism.
This PA uses just-in-time concepts. It also uses the modular as well as the
non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
you are submitting an application with direct costs in each year of $250,000
or less, use the modular format. Otherwise follow the instructions for non-
modular research grant applications. This program does not require cost
sharing as defined in the current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage your inquiries concerning this PA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research, and financial or grants management issues:
o Direct your questions about scientific/research issues to:
Leroy M. Nyberg, Jr., Ph.D., M.D.
Director, Urology Programs
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd, Room 627
Bethesda, MD 20892
Telephone: (301) 594-7717
Email: ln10f@nih.gov
Tracy L. Rankin, Ph.D.
Reproductive Sciences Branch
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Blvd, Room 8B01
Bethesda, MD 20892
Telephone: (301) 435-6979
E-mail: rankint@mail.nih.gov
Patricia D. Reichelderfer, Ph.D.
Contraceptive and Reproductive Health Branch
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Blvd., Room 8B13
Bethesda, MD 20892
Telephone: (301) 435-6991
E-mail: pr20f@nih.gov
o Direct your questions about financial or grants management matters to:
Ms. Helen Ling
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 732
Bethesda, MD 20892
Telephone: (301) 594-8857
FAX: (301) 480-3504
Email: hl12d@nih.gov
Ms. Mary Ellen Colvin
Grants Management Specialist
National Institute of Child Health of Human Development
6100 Executive Blvd, Room 8A17M
Bethesda, MD 20892
Telephone: (301) 496-1304
E-mail: mc113b@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 710-0267,
Email: GrantsInfo@nih.gov.
APPLICATION RECEIPT DATES: Applications submitted in response to this program
announcement will be accepted at the standard application deadlines, which
are available at http://grants.nih.gov/grants/dates.htm. Application
deadlines are also indicated in the PHS 398 application kit.
SPECIFIC INSTRUCTIONS FOR R21 APPLICATIONS: All application instructions
outlined in the PHS 398 application kit are to be followed, with the
following requirements for R21 applications:
1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME"
concepts, with direct costs requested in $25,000 modules, up to the total
direct costs of $275,000 for the combined two year award period.
2. Although preliminary data are not required for an R21 application, they
may be included.
3. Sections a-d of the Research Plan of the R21 application may not exceed
15 pages, including tables and figures.
Appendix. Use the instructions for the appendix detailed in the PHS 398
except that no more than 5 manuscripts, previously accepted for publication,
may be included.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in a modular grant
format. The modular grant format simplifies the preparation of the budget in
these applications by limiting the level of budgetary detail. Applicants
request direct costs in $25,000 modules. Section C of the research grant
application instructions for the PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step
guidance for preparing modular grants. Additional information on modular
grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.
SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:
Applications requesting $500,000 or more in direct costs for any year must
include a cover letter identifying the NIH staff member within one of NIH
institutes or centers who has agreed to accept assignment of the application.
Applicants requesting more than $500,000 must carry out the following steps:
1) Contact the IC program staff at least 6 weeks before submitting the
application, i.e., as you are developing plans for the study;
2) Obtain agreement from the IC staff that the IC will accept your
application for consideration for award; and,
3) Identify, in a cover letter sent with the application, the staff member
and IC who agreed to accept assignment of the application.
This policy applies to all investigator-initiated new (type 1), competing
continuation (type 2), competing supplement, or any amended or revised
version of these grant application types. Additional information on this
policy is available in the NIH Guide for Grants and Contracts, October 19,
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the checklist, and five signed photocopies in one
package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
APPLICATION PROCESSING: Applications must be mailed on or before the receipt
dates described at
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will
not accept any application in response to this PA that is essentially the
same as one currently pending initial review unless the applicant withdraws
the pending application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude the
submission of a substantial revision of an application already reviewed, but
such application must include an Introduction addressing the previous critique.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.
PEER REVIEW PROCESS
Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
convened in accordance with the standard NIH peer review procedures
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific
and technical merit.
As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate national advisory council
or board.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to discuss the following
aspects of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these criteria
in assigning the application's overall score, weighting them as appropriate
for each application. The application does not need to be strong in all
categories to be judged likely to have major scientific impact and thus
deserve a high priority score. For example, an investigator may propose to
carry out important work that by its nature is not innovative but is
essential to move a field forward.
SIGNIFICANCE: Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced? What
will be the effect of these studies on the concepts or methods that drive
this field?
APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?
INVESTIGATOR: Is the investigator appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?
ENVIRONMENT: Does the scientific environment in which the work will be done
contribute to the probability of success? Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation
in the proposed research will be assessed. (See criteria included in the
section on Federal Citations, below).
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups
(and subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the sections on
Federal Citations, below).
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to
be used in the project, the five items described under Section f of the PHS
398 research grant application instructions (rev. 5/2001) will be assessed.
SPECIAL CONSIDERATION FOR THE R21 APPLICATION: The NIH R21
exploratory/developmental grant is a mechanism for supporting novel
scientific ideas or new model systems, tools or technologies that have the
potential to significantly advance our knowledge or the status of health-
related research. Because the research plan is limited to 15 pages, an
exploratory/developmental grant application need not have background material
or preliminary information as one might normally expect in an R01
application. Accordingly, reviewers will focus their evaluation on the
conceptual framework, the level of innovation, and the potential to
significantly advance our knowledge or understanding. Reviewers will place
less emphasis on methodological details and certain indicators traditionally
used in evaluating the scientific merit of R01 applications including
supportive preliminary data. Appropriate justification for the proposed work
can be provided through literature citations, data from other sources, or,
when available, from investigator-generated data. Preliminary data are not
required for R21 applications.
ADDITIONAL CONSIDERATIONS
DATA SHARING: The adequacy of the proposed plan to share data.
BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research.
AWARD CRITERIA
Applications submitted in response to a PA will compete for available funds
with all other recommended applications. The following will be considered in
making funding decisions:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components
involving Phase I and II clinical trials must include provisions for
assessment of patient eligibility and status, rigorous data management,
quality assurance, and auditing procedures. In addition, it is NIH policy
that all clinical trials require data and safety monitoring, with the method
and degree of monitoring being commensurate with the risks (NIH Policy for
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12,
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43).
All investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research -
Amended, October, 2001," published in the NIH Guide for Grants and Contracts
on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/
NOT-OD-02-001.html); a complete copy of the updated Guidelines are
available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended
_10_2001.htm. The amended policy incorporates: the use of an NIH
definition of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language governing
NIH-defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase III
clinical trials that: a) all applications or proposals and/or protocols must
provide a description of plans to conduct analyses, as appropriate, to address
differences by sex/gender and/or racial/ethnic groups, including subgroups if
applicable; and b) investigators must report annual accrual and progress in
conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The
Department of Health and Human Services (DHHS) issued final modification to
the "Standards for Privacy of Individually Identifiable Health Information",
the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable
health information, and is administered and enforced by the DHHS Office for
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified
under the Rule as "covered entities") must do so by April 14, 2003 (with the
exception of small health plans which have an extra year to comply).
Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including
a complete Regulation Text and a set of decision tools on "Am I a covered
entity?" Information on the impact of the HIPAA Privacy Rule on NIH
processes involving the review, funding, and progress monitoring of grants,
cooperative agreements, and research contracts can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This PA
is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284)
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All
awards are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement. The NIH Grants
Policy Statement can be found at
http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in
certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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