Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

The Role of Dysbiosis in Cardiovascular, Pulmonary and Hematological Complications During HIV Infection (R01)

Activity Code

R01 Research Project Grant

Announcement Type


Related Notices


Funding Opportunity Announcement (FOA) Number


Companion Funding Opportunity


Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.838, 93.837, 93.839, 93.840, 93.233

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to invite basic research project grant applications for HIV Microbiome Centers to perform investigations on the role of HIV-induced dysbiosis and how this imbalance may induce and/or contribute to the occurrence of heart, lung, or blood (HLB) co-morbidities in HIV positive individuals. This FOA will support mechanistic studies that will use in vitro, in vivo, ex vivo, and in silico models applied to HIV research. The goal is to provide the critical basic science foundation to guide early translational approaches to understanding HIV-related HLB conditions in adults and children. This FOA also encourages multidisciplinary collaborations among scientists in a wide range of disciplines including (but not limited to), cardiology, pulmonology, hematology, immunology, '-omic' sciences, infectious disease, microbiology, biotechnology, and bioinformatics.

Key Dates
Posted Date

July 11, 2016

Open Date (Earliest Submission Date)

October 8, 2016

Letter of Intent Due Date(s)

October 8, 2016

Application Due Date(s)

November 8, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

November 8, 2016 by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Scientific Merit Review

March 2017

Advisory Council Review

May 2017

Earliest Start Date

September 2017

Expiration Date

November 9, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Dysbiosis is defined as the deviation from the normal resident microbial community composition found in a healthy population of individuals. During early stages of HIV infection, the intestinal epithelial barrier suffers extensive damage, repair of epithelial cells is impaired by altered expression of genes involved in the machinery of regeneration, and many genes involved in inflammation are upregulated. These alterations lead to a general state of dysbiosis, including translocation of microbes and microbial constituents that are normally contained within the gut into the systemic circulation where they can induce inflammation and pathobiology of distal organs. Dysbiosis likely contributes to the cardiovascular, pulmonary, and hematological complications seen in HIV infection and may be an important cause of poor health outcomes. Although dysbiosis is generally associated with gut microbial alterations, microbial imbalance is not unique to the gut. In advanced states of HIV infection, individuals with lower CD4 cell counts have an altered alveolar microbiome characterized by a loss of species richness and diversity, and have increased amounts of signature bacteria associated with chronic lung inflammation after years of antiretroviral therapy (ART). Furthermore, specific metabolic profiles in the lung appear to correlate with bacterial organisms that are known to play a role in the pathogenesis of pneumonia in HIV-infected individuals, suggesting that dysbiosis may have a functional metabolic impact on the lung.

Dysbiosis may play a role in some or all of the following complications for which HIV-infected individuals are at very high risk:

  • Cardiovascular disease: Gut microbiota plays a critical role in the development and maintenance of physiological responses within the host. Dysbiosis has been implicated in atherosclerosis and cardiovascular disease in HIV(-) individuals, through linkage between L-carnitine ingestion, gut microbiota metabolism, atherosclerosis formation, and CVD risk. In HIV(+) individuals, chronic inflammation due to dysbiosis may contribute to the formation of the atherosclerotic plaque, perhaps through altered tryptophan metabolism and increased plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), two established markers of disease progression. Studies in HIV(+) patients have shown that higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events.
  • Pulmonary complications: Gut dysbiosis can lead to severe defects in pulmonary immune responses and reduced ability to clear common lung pathogens such as influenza. Therefore, it is reasonable to hypothesize that gut and lung dysbiosis in HIV-infected subjects with advanced disease may contribute to chronic inflammation and lung complications even with long term ART treatment. Hence, understanding the impact of dysbiosis in the lungs of HIV-infected individuals, who are at high risk of developing pulmonary complications, is a critical research objective.
  • Blood abnormalities: Anemia is also a common feature of HIV-related disease and a strong, independent predictor of morbidity and mortality. Although anemia often responds to combination antiretroviral therapy (ART), some patients remain anemic despite therapy and refractory anemia predicts a poorer prognosis despite responsiveness to the drug by other measures. As with cardiovascular and pulmonary complications, it is possible that activation of proinflammatory pathways by dysbiosis and bacterial translocation is a major cause of anemia in HIV, especially that which persists in the face of ART.
Research Scope and Objectives

The main hypothesis to be tested by research supported through this FOA is that HIV-induced dysbiosis affects host homeostasis (such as immune function, metabolism, hormonal regulation, etc.) leading to or accelerating the development of HIV-related heart, lung and/or blood (HLB) comorbidities. Elucidation of mechanisms linking dysbiosis to HLB comorbidities will identify putative targets for therapeutic intervention and potentially enhance the length and quality of life for patients living with HIV. Research to address this main hypothesis will necessarily require collaborations across multiple disciplines as well as the use of a variety of advanced technologies to characterize microbiomes and microbiome-host interactions. It is anticipated that improved sampling methods and standards will be critical to these studies.

Microbiome research has successfully identified associations between dysbiosis and obesity, heart disease, and other metabolic disorders and has begun to pave the way for efforts to improve health by targeting the microbiome. Work supported through this FOA will extend this prior research by probing the pathobiological mechanisms responsible for these associations, identifying potential therapeutic interventions, and suggesting which patients may be most likely to benefit from those interventions. Because HIV infected individuals are now living long enough to manifest HLB comorbidities that represent a significant health burden, research on the role of the microbiome in the context of HIV-associated HLB diseases is timely and expected to be impactful.

Scientific knowledge to be achieved through research supported by the FOA

HIV is capable of drastically altering the immune system, the gastrointestinal environment and gut microbiota, and the lung microbiome in advanced stages of disease, and abundant data exist implicating the human microbiome in the initiation and amplification of multiple inflammatory conditions. It is also well known that HIV infection is associated with increased risk for a variety of cardiopulmonary and hematological complications that involve inflammatory processes. Nevertheless, mechanistic connections between HIV-induced alterations in microbiome and HLB diseases still need to be demonstrated and examined in detail. Research supported by this FOA will explore the functional roles of microbes and/or microbial-derived bioactive molecules and will examine the role of dysbiosis in the pathogenesis of HLB complications of HIV infection. Mechanistic studies may employ in vitro, in vivo, ex vivo, or in silico models. The increased knowledge gained in the microbiome field in recent years, applied to the pathobiology of HIV infection, presents a unique opportunity to investigate the impact of unbalanced microbial communities on heart, lung and blood diseases in HIV patients whether or not they are undergoing ART therapy. Better understanding of this relationship will allow for future development of targeted manipulation of the gut microbiota in HIV(+) individuals; for example, selected pro- and/or pre-biotics, antibiotics, or diet modifications might allow modulation of microbiota composition to one associated with preserved immunity, normal plasma-associated biomarkers, reduced opportunistic infections, and decreased HLB complications.

In 2015, the NHLBI convened a Working Group on Advancing HIV/AIDS Research in Heart, Lung, and Blood Diseases. The group was comprised of basic and clinical scientists and charged with identifying research priorities in HIV-related heart, lung, blood, and sleep (HLBS) diseases. The need for a detailed analysis of the microbiome, virome, and fungome at all stages of HIV infection and studies of the systemic effects of microbiome dysregulation on the onset of disease were identified as critical gaps in the current knowledge of the pathophysiology of HIV infection. This FOA was developed to support studies that will address these targeted recommendations from the Working Group, especially the role of dysbiosis in onset and progression of HLB co-morbidities of HIV infection.

Specific Areas of Research Interest

The following are examples of research topics responsive to this FOA. These are examples only; applicants should not feel limited to the subjects mentioned and are encouraged to submit other topics pertinent to the objectives of this FOA.

  • Mechanisms underlying the development of atherosclerotic plaques and other cardiovascular complications due to HIV-related alterations in intestinal microbiota and/or microbial derived metabolic products.
  • Mechanisms whereby HIV-related changes in the lung/gut microbiome may lead to lung damage and/or remodeling. For example, dysbiosis of the gut microbiome might produce systemic metabolites and inflammatory mediators that activate pulmonary macrophages.
  • Interactions between the altered microbial communities and the epithelium in the lung/airways.
  • Role of the altered gut/lung microbiome composition in shaping lung mucosal immunity.
  • Effect of the altered microbiome composition on hematologic and immunologic health of patients with blood diseases.
  • Direct role that HIV infection plays in affecting the lung flora and immune system and subsequent pulmonary complications.
  • Effects of the microbiome of HIV infected patients on endothelium, coagulation and thrombus formation.
  • Studies to identify microbial metabolites or signaling molecules produced by microorganisms that affect host pathways or transcriptional networks leading to HLB complications.
  • Modulatory role of the microbiome on medical and pharmacological interventions such as transfusion, mechanical intubation, hematopoietic stem cell transplantation (HSCT), and treatment of HIV infection with anti-retroviral therapy.

Applicants are encouraged to incorporate state of the art omics technologies as they apply to microbiome research (e.g., genomics, proteomics, and metabolomics), bioinformatics tools, advanced immunologic and microbiologic methods, and state-of-art techniques for detecting and characterizing HIV-related HLB co-morbidities. Studies should include measurements of both microbiome and HLB functions or abnormalities, and studies should be designed to explore mechanistic relationships between these measurement domains.

Studies are expected to involve human subjects with HIV infection or biospecimens derived from human subjects with HIV. Use of banked biospecimens from existing cohorts is acceptable. Animal models are permitted together with parallel human studies as needed to test specific mechanistic hypotheses.

Other Resources

Research applications that can leverage cohorts or populations from other programs such as global AIDS programs are encouraged. Stored samples, such as those in the NHLBI repository ( may be of interest.

Specific examples of existing research infrastructure that could be leveraged include (but are not limited to):

Research topics that are NOT responsive to this FOA
  • Applications that do not focus on HIV-related heart, lung, or blood research.
  • Applications that propose patient-oriented research such as clinical trials or epidemiological research.
  • Applications focused solely on characterization of the microbiome (e.g.: 16S analysis only)

Non-responsive applications will not be reviewed.

Program Structure

In addition to conducting their own individual projects as proposed in their grant applications, grantees will be expected to participate with other HIV Microbiome Centers that are part of this program in the development and prioritization of common protocols for collaborative research on the role of dysbiosis in HIV-related HLB comorbidities. Consistent with achieving the goals of the program, applicants are expected to agree to share data, models, and biospecimens. They will be responsible for conducting the research: subject recruitment and implementation of all study procedures, genomic, proteomic and other omics studies, analyzing and interpreting research results, and disseminating research findings.

NHLBI plans to arrange annual one-day grantee meetings to review progress and to encourage discussion and exchange of research ideas, methods, and reagents among the investigators. At these meetings, awardees will be expected to share their results and help evaluate progress. Attendance at these meetings is required.

Success of the program will be measured by evaluation of annual grantee progress reports, annual grantee meetings, development of collaborative projects and publications/presentations. In addition, recruitment, completion of data collection and analysis, and the sharing of data with investigators outside the program as appropriate will be monitored at regular intervals by NHLBI.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed


The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NHLBI intends to commit total costs of $2,495,000 per year for fiscal years 2017 through 2020 to fund 5 awards.

Award Budget

Application budgets are limited to a maximum of $310,000 direct costs in any year. Budgets need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 4 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)


  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession


  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Applicants must have an active DUNS number and SAM registration in order to complete the registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review, NHLBI
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional instructions also apply:

  • Applicants are strongly encouraged to use a multiple Program Director/Principal Investigator (PD/PI) option ( to provide strong leadership and facilitate collaborations between HLB, HIV, and microbiome experts for a multi-disciplinary approach.
  • These collaborations are likely to require multiple fields of expertise. Where applicable to the proposed specific research aims, describe relevant expertise and experience in areas such as infectious diseases, immunology, microbiology, omics (e.g., genomics, proteomics, metabolomics, and metagenomics), molecular biology, microbial ecology, bioinformatics, physiology, and/or computational modeling. Describe how proposed personnel will collaborate to provide relevant expertise.
  • Early career investigators are highly encouraged to apply.
R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Clearly describe the specific aims indicating how completion of each aim will support and advance the objectives of this FOA.

Research Strategy: Describe how the proposed research project will investigate the fundamental mechanisms by which dysbiosis may play a role in cardiovascular, pulmonary and hematological complications during HIV infection. Applicants addressing the role of dysbiosis on HIV-related pulmonary, cardiovascular or blood comorbidities must propose functional experiments at the molecular/cellular level and/or experiments at the tissue/organ level. Validation in appropriate animal models will be acceptable but animal studies should be used in parallel with human studies. Any purely descriptive or correlative studies must target identification of new microbial elements in blood, lung mucosal surfaces, or vasculature and must include the study of the molecular and physiological mechanisms by which these newly identified elements may impact heart, lung, or blood host cells. In addition, hypotheses linking the two levels aforementioned should be addressed. Experiments must be proposed that allow the investigator(s) to delineate the effects of microbial imbalance as influencing, inducing or causing a marked effect in comorbidities, and how this knowledge could inform treatment should be presented.

Applications must describe the following points:

  • How the hypothesis tested is relevant to clinically defined HIV-related lung, heart or blood comorbidities or the intensification of such comorbidities;
  • How the hypothesis to be tested is relevant to the health of HIV(+) individuals undergoing or not undergoing anti-retroviral therapy;
  • How the proposed experiments will demonstrate or clarify the role of dysbiosis in HIV-related heart, lung or blood comorbidities;
  • If applicable, analysis methods, sample methods and storage, cohorts, and recruitment strategy including milestones, timeline, and strategies to overcome pitfalls and limitations;
  • Plans to facilitate communication and collaboration among multi-disciplinary investigator teams (i.e., team meetings, teleconferences, websites);
  • Clear description and evidence of access to any new or archived specimens and data and to animal models (if applicable), as required for the proposed studies. To the extent possible, applications that propose to use existing samples are strongly encouraged. If existing samples are used, investigators must indicate that the stored samples were collected, handled, and stored in a manner appropriate for the proposed measurements and that the phenotypic data associated with the biospecimens is sufficient to allow testing of associations with HLB abnormalities or disease.
  • Applications should include a statement indicating willingness of the PD(s)/PI(s) to participate in one meeting each year to be held in the Bethesda, Maryland area to encourage and facilitate the exchange of information among participating investigators.

Letters of Support: Include any letters of support. This may include letters of support from leadership of leveraged programs or existing resources that will be utilized, if applicable.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.


Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

How strong is the likelihood that the proposed hypothesis will lead to important information regarding the role of microbial imbalance on heart, lung and blood comorbidities? What is the likelihood that the research proposed will advance understanding of the role of the dysbiosis in the onset of heart, lung, and blood co-morbidities? 


Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA:

Does the application include plans for multi-disciplinary collaboration from investigators with HIV, HLB and microbiome expertise?


Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific for this FOA:

Does the proposed research utilize state of the art approaches in novel ways to evaluate the role of dysbiosis in the context of HIV infection and the onset of heart, lung and blood comorbidities?


Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Specific for this FOA:

If existing resources, samples or programs are not leveraged, does the application sufficiently justify the creation of new resources or utilization of new samples? Have the investigators provided a reasonable timeline of when they will be able to initiate and complete research, including any timeline requirement from the leveraged programs, if used?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?


Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.


Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.


Not Applicable


Not Applicable


Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung, and Blood Advisory Council. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see; and Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free) Customer Support (Questions regarding registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: (preferred method of contact)
Telephone: 301-945-7573

Scientific/Research Contact(s)

Lis Caler, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0222

Peer Review Contact(s)

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270

Financial/Grants Management Contact(s)

Beckie Chamberlin
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0183

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

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 Part 52 and 45 CFR Part 75.

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