Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Background

The National Institutes of Health (NIH) of the United States (U.S.) Department of Health and Human Services (HHS) supports international collaborative biomedical research to advance science and expand biomedical knowledge.  Scientific cooperation between the U.S. and the Republic of South Africa was initiated in 1995 and has grown in recent years. Recognizing that enhanced cooperative biomedical research would be of mutual benefit to the U.S. and South Africa, the NIH Director and the President of the South African Medical Research Council (SAMRC) signed a Memorandum of Understanding (MOU) in January 2013 to develop the U.S.-South Africa Program for Collaborative Biomedical Research.  Phase 1 of this program included awards made in response to RFA-AI-14-009, RFA-AI-14-010, RFA-AI-14-018, RFA-AI-16-039, RFA-AI-16-040, RFA-AI-16-082, and RFA-AI-16-083. Phase 2 of this program included awards made in response to RFA-AI-19-022, RFA-AI-19-023,  RFA-AI-19-024, and RFA-AI-19-025. The NIH and MRC have developed strategic plans for continued collaboration.  Both the NIH and SAMRC have allocated resources to support the third phase of this program.  Phase 3 will solicit applications for research on HIV/AIDS, HIV/AIDS co-morbidities and co-infections, HIV/AIDS-associated implementation science, and HIV/AIDS-associated data science.

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to establish Phase 3 of the U.S.-South Africa Program for Collaborative Biomedical Research.  Research areas supported under this program include HIV/AIDS, HIV/AIDS co-morbidities and co-infections, HIV/AIDS-associated implementation science, and HIV/AIDS-associated data science.

The intent of this NOFO is to foster, stimulate, and/or expand basic, translational, behavioral, and applied research that will advance scientific discovery and engage U.S. and South African researchers working collaboratively in the areas of HIV/AIDS, HIV/AIDS co-morbidities and co-infections, and HIV/AIDS and associated implementation science and data science. Proposed research should reflect the highest possible scientific standards, as well as shared interests, international and local public health needs and priorities, and involve mutually advantageous collaborations among institutions, including participating communities and other partners. U.S. and South African investigators working with their institutions and in collaborative partnership will prepare and submit a single joint application.  Applications must include at least one South African Program Director/Principal Investigator (PD/PI) from an eligible institution from South Africa (the applicant organization) and at least one collaborator from a U.S. institution/organization.

An overarching goal of this bilateral program is to engage scientists in South Africa from historically disadvantaged institutions (HDIs).  Despite tremendous advancements, there remains unequal participation in the national scientific research agenda in South Africa. NIH and SAMRC encourage South African institutions to enhance the participation of researchers from HDIs, including individuals from groups identified as underrepresented in the biomedical, clinical, behavioral, and social sciences. Underrepresented groups in South Africa include African, Coloured and Indian population groups in South Africa.  One of the major tenets of the SAMRC and the South Africa Department of Higher Education and Training is the development of research capacity.  Transformation is central to the SAMRC’s strategy, especially transformation in the research landscape.

Scientists from South African HDIs and other South African Universities of Technology and/or scientists from the African, Coloured, or Indian population groups are encouraged to work with their institutions to apply as PD/PIs. In addition, and complementary to the proposed research project, applicants are highly encouraged to include in their applications an optional career enhancement partnership for fostering and enhancing research skills and experience of scientists from under-resourced institutions (HDIs and other South African Universities of Technology) that have a demonstrated commitment to biomedical research but have limited resources or experience. The goal is to develop collaborations that will expose scientists from these institutions to rigorous research experiences. Please note, however, that consistent with NIH practice and U.S. federal law, funded programs may not use the race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status) of a prospective researcher as an eligibility or selection criteria. The race, ethnicity, or sex of researchers or prospective researchers will not be considered by NIH in the application review process or when making funding decisions.   

This NOFO encourages New Investigators and Early Stage Investigators from the U.S. and South Africa to participate in this research program.

Research Objectives

Basic, translational, behavioral, clinical, preventive, data science, implementation, and/or epidemiological research may be proposed under this program.  HIV-related research is encouraged in accordance with the NIH Director's statement describing the NIH's overarching HIV research priorities, and the accompanying Guide NOTICE.

Specific Research Areas of interest include:

Reduce Incidence of HIV (Prevention)

• Understanding HIV transmission dynamics among different populations and age groups, and the geographic distribution of HIV prevalence and incidence.
• Informing development of new biomedical prevention strategies through understanding host/virus interactions associated with HIV acquisition, establishment of infection and disease progression.
• Prevention of perinatal HIV-transmission through primary prevention of HIV transmission, improvement in HIV viral suppression during perinatal periods, and enhanced infant prophylaxis and maternal viral suppression through the breastfeeding period.
• Voluntary medical male circumcision (VMMC) programs and impact in different populations, including culturally competent practices.
• Effects of maternal HIV and antiretroviral treatment on HIV-exposed uninfected children.
• HIV prevention among key and priority populations outlined in the 2023-2028 National Strategic Plan for HIV, TB, and Sexually Transmitted Infections (STIs): adolescents and young people, particularly adolescent girls and young women (AGYW); survivors of sexual/gender-based violence; sex workers and their clients; sexual and gender minority populations; people who use alcohol and/or other substances; and people in prisons and other closed settings.
• HIV prevention in adolescent/young adult populations, including strategies to achieve high uptake and adherence to pre-exposure prophylaxis (PrEP).
• The role of food insecurity and nutrition, housing instability, and other social determinants of health in prevention, care, and treatment of HIV/AIDS.
• Novel strategies to enhance uptake of HIV testing and sustained linkage to care through differentiated service delivery, including community-based approaches, among key and priority populations in South Africa as outlined in the 2023-2028 National Strategic Plan for HIV, TB, and Sexually Transmitted Infections (STIs).
• Risk factors, causes and sequelae of genital inflammation and its role in HIV acquisition in women.
• The potential role of broadly neutralizing antibodies in HIV prevention and treatment.
• The potential role of long-acting injectable technologies in HIV prevention and treatment.
• Tailored interventions for key populations.
• New HIV testing technologies for self-testing and viral load monitoring, and innovative testing strategies.
• Examination of pathophysiology and direction of effects between mental health and HIV acquisition as well as broader HIV outcomes.
• Motivations and reasons for age-disparate sexual partnering (>10 years age difference) and its role in HIV acquisition.
• Strategies that can reduce the impact of stigma, discrimination, gender bias, prejudice, homophobia, and transphobia on HIV prevention, care, and treatment.
• Strategies that can strengthen demand for HIV services that promote accurate information dissemination and counter disinformation among diverse populations.

Develop Next-Generation HIV Therapies (Treatment and Care Continuum)

• Best approaches to optimizing durability of antiretroviral therapy (ART) regimens and adherence support.
• Strategies on testing, linkage, adherence to HIV treatment, and retention in care, including in adolescent/young adult populations and programmatic combinations with contraception, and including use of mobile, digital, and telehealth technologies and platforms.
• Approaches to monitoring ART treatment, including consequences of long-acting injectable ART.
• Strategies to improve annual viral load testing rates for people on ART.
• Optimal programmatic combinations of HIV treatment and contraception.
• Differentiated care, including adherence clubs and alternate drug delivery.
• Laboratory-based research utilizing clinical samples collected from observational cohorts or clinical trials to advance testing of diagnostics and/or development of biomarkers applicable to HIV.

Research Toward HIV Cure

• Research toward a "functional cure" for adult and/or pediatric HIV and elimination of viral reservoirs.
• Basic research focused on persistent HIV infection and curative strategies.

Address HIV-Associated Co-Morbidities, Co-Infections, and Complications

• Impact and management of HIV and TB infection, along with strategies that promote the integration and support of combined HIV and TB care, including novel approaches to improve adherence to TB treatment among people with HIV (PWH).
• Understanding the immune and/or mycobacterial factors associated with TB pathogenesis among PWH, including subclinical TB and/or post-TB cardio-pulmonary disease.
• Chronic inflammation in treated HIV disease.
• Approaches to integrate chronic disease and mental health care into HIV/AIDS care services.
• Basic research focused on the influence of HIV infection on non-communicable diseases in PWH.
• Discovery, development, and/or testing of diagnostic and/or prognostic biomarkers, including markers of drug resistance, host directed therapies, and vaccines (both preventive and therapeutic) that can improve outcomes for PWH.

Cancer

• Epidemiology of cancer in PWH in the era of antiretroviral therapy.
• Studies identifying biological differences between tumors occurring in PWH and without HIV.
• Understanding interactions of HIV with human papilloma virus (HPV), human herpes viruses (EBV and HHV-8), hepatitis B and C viruses, herpes simplex virus (HSV) and other oncogenic viral co-infections that lead to increased cancer risks.
• Studies on pathogenesis and pathobiology of virally associated cancers in PWH.
• Strategies for optimizing screening, diagnosis, prevention, and treatment of cancer in PWH.
• Studies on complications and outcomes of treating cancers among PWH.
• Studies that enhance our understanding of the role stigma plays in accessing cancer screening and care as well as its impact on survivorship in PWH.
• Studies identifying strategies for optimizing the integration of HIV care with cancer-related screening and treatment delivery.

Behavior, Mental Health, Substance Use, and HIV Risk

• Integrative approaches to treating and preventing mental health and substance abuse co-morbidities in HIV, especially in women exposed to violence or abuse, and youth.
• Studies to test novel approaches to integrate screening for mental symptoms or disorders into HIV prevention or care, with referral and linkages to appropriate levels of mental health care in South Africa.
• Studies on biomarkers to assess the status of mental health, HIV, and other comorbidities.
• Cost-effectiveness studies to assess economic benefits of the integration of HIV and mental health system approaches.
• Mechanisms (e.g., neurotoxic, epigenetic) underlying genetic, physiological, environmental, social, cultural, and economic factors and interactions that affect brain function or development and result in neurobehavioral outcomes (e.g., expression of cognitive impairment, coping, adaptation, response to intervention).
• Evaluation of the interaction among neuropsychiatric co-morbidities in HIV and age-related cognitive, physical, and functional decline; and how this is affected by socio-environmental and other factors.
• Neurobehavioral sequelae of perinatal and in utero exposure to HIV, other HIV co-infections, and antiretroviral and related treatments.
• Studies on the relationship between stress and HIV (e.g., 1. investigation of stress-induced immune changes and implications for HIV; 2. impact of stress and HIV on cognitive impairment; 3. psychosocial dynamics impacted by HIV and stress; and 4. implications of stress on HIV reservoirs).
• Longitudinal outcomes of the co-occurrence of HIV, alcohol and/or other substance use, and other mental health comorbidities (e.g., depression), and associated genetic, epigenetic, neurobiological, and environmental mechanisms.
• The role of alcohol and/or other substance use in physical and psychological trauma, including gender-based violence and rape.
• Evaluation of the effectiveness of integrating alcohol and/or harm reduction programs into HIV prevention, treatment and care programs, and their impact on the overall HIV epidemic.
• Studies on the link between alcohol use and adherence to HIV medication: 1. development of longer-lasting, less toxic medication regimens for PWH who continue to drink; and 2. assessment, reduction, and prevention of related pathophysiology for organ and tissue injury.
• Evaluation of the effectiveness of health system-based and/or policy-level interventions on HIV-related health outcomes.
• Studies on the prevalence and correlates of alcohol use among pregnant women with HIV in South Africa and how effective interventions may be disseminated to improve both maternal and fetal outcomes.
• Studies on the relationship between cognitive performance and alcohol consumption in people with HIV, and the impact on the development and uptake of interventions to prevent or treat HIV/AIDS.

Implementation Science/Data Science

• Implementation science research to improve the adoption, implementation, and sustainment of evidence-based or evidence-informed HIV prevention and/or care interventions aimed at improving health outcomes in the context of clinical and community settings for pediatric, adolescent, and young adult, and adult populations.
• Studies designed to enhance HIV prevention providers’ capacity to assist people in high-incidence or priority populations (e.g., via systems, providers, operational tools)
• Studies of systemic interventions to influence organizational structure, climate, and culture, to promote organizational readiness and capacity for intervention adoption, and implementation with fidelity and effectiveness.
• Studies to understand the benefit of varying training methodologies (e.g., didactic training, clerkship, on-site mentoring, on-going consultation, internet-based courses) to prepare providers to offer HIV prevention and treatment services.
• Studies to optimize the implementation (uptake, effectiveness, efficiency) of individual and/or combination prevention evidence-based interventions (e.g., behavioral risk-reduction, voluntary medical male circumcision [VMMC], PrEP, condom provision), designed to maximize the optimal targeting, uptake, coverage, effectiveness, and efficiency of service provision.
• Studies to optimize the implementation (uptake, effectiveness, efficiency) of individual and/or combination interventions designed to maximize HIV testing, linkage to HIV care, earlier ART initiation, adherence, and engagement HIV testing, which could include advancements in approaches and technologies.
• Studies of the impact of varying models of differentiated HIV care on HIV care continuum outcomes, which could include studies to evaluate optimal approaches to integrate community care delivery to include HIV prevention, care, and treatment with related services (mental health, substance use disorders, sexually transmitted infections, family planning, prenatal care, malaria, and/or tuberculosis).
• Studies to test and evaluate implementation of interventions that address social and structural determinants of health and their impact on HIV prevention, testing, treatment initiation, and continuity.
• Studies designed to enhance understanding of the epidemiologic contexts for targeted interventions (e.g., accurate rates of testing, linkage, initiation and viral suppression that indicates gaps and targets for intervention).
• Studies of cost and cost-effectiveness of intervention delivery in real-world settings, including the cost-effectiveness of alternative treatments, services, or payment structures for the provision of services
• Studies to inform the sustainment and/or sustainability of HIV interventions.
• Comparative effectiveness research focused on understanding factors related to early detection, patient engagement and retention in appropriate alcohol and HIV care and achieving and maintaining optimal treatment responses in diverse settings.
• Studies to improve outcomes for PWH accessing emergency care.
• Modeling and testing alternative implementation approaches to improve uptake and scaling-up of effective interventions and reduce HIV disease transmission and progression in key populations.
• Strategies to standardize use of unique patient identifiers for all patient records, tests, and health care engagement.
• Development of data harmonization strategies to build a robust data analysis infrastructure for the application of large-scale data science approaches and technologies.
• Implementation research to determine effective combination prevention strategies for both primary and secondary prevention.

Applications proposing the topics below will be considered non-responsive and will not be reviewed:

• Projects proposing Phase III or Phase IV clinical trials.
• Research using select agents.
• Applications without the required collaborative partnership (at least one South African PD/PI from an eligible institution from South Africa and at least one collaborator from a U.S. institution/organization).

For more information, please refer to specific Questions and Answers located at this link: https://www.niaid.nih.gov/grants-contracts/questions-and-answers-US-South-Africa-collaborative-biomedical-research-phase-3-HIV-AIDS.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Applicant Organizations must be from South Africa, as described below

• An eligible National Research Foundation (NRF) South African Institution is a recognized South African public higher education or research institution such as a university, university of technology, science council, museum or other research institution as declared by the Department of Science and Innovation. 

• Historically disadvantaged institutions (HDIs) include:
  • Mangosuthu University of Technology
  • Sefako Makgatho Health Science University
  • University of Fort Hare
  • University of Limpopo
  • University of the Western Cape
  • University of Venda
  • University of Zululand
  • Walter Sisulu University

• South African Universities of Technology include:
  • Cape Peninsula University of Technology
  • Central University of Technology
  • Durban University of Technology
  • Sol Plaatje University
  • Tshwane University of Technology
  • University of Mpumalanga
  • Vaal University of Technology

Non-domestic (non-U.S.) Entities (Foreign Organizations) are 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.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. 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.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov 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.

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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply-Application Guide.

Required Collaborative Partnership

• A South African investigator(s) must serve as the PD/PI. Additional South African investigator(s) may serve as part of a multi- PD/PI team or collaborators.
• At least one U.S. investigator(s) must serve as collaborator with the South African PD/PI (or the South African multi-PD/PI team).

The South African PD/PIs must be either permanently employed at an eligible South African research institution or be in a long-term contract (at least for the minimum of the duration of the project).  Postgraduate students, full or part-time, are not eligible to serve as PDs/PIs.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.

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:

Holly Curtis, PhD
Office of Global Research
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5666
Email: [email protected] 

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed with the following additional instructions:

Facilities and Other Resources: In a clearly labeled section, applicants should include a description of project-specific resources, naming those resources that are provided by the PD/PIs and the collaborating partners, and a describe the plan for sharing and distribution of project-specific resources among the individuals performing specific elements of the research project (e.g., individual contributions of specific reagents, patient samples, compounds, and access to populations for epidemiologic studies).

Other Attachments: Two separate attachments should be submitted for this section: a Collaboration Plan and a Financial Management and Oversight Plan.

A Collaboration Plan (pdf file named Collaboration Plan) should be included that describes the interactions among the recipients (the South African PD/PIs and collaborators) in terms of plans for communications, processes for making decisions on scientific direction and planning activities, procedures for resolving conflicts, and fostering collaborations with the community, if applicable. Outline the combined roles and responsibilities of all participating partners in the research, including contingency plans addressing solutions to setbacks or delays.  Describe how the U.S. and South African investigators will draw on their unique expertise related to the research project.

A Financial Management and Oversight Plan (pdf file named Financial Plan) should be included that describes plans for implementing subcontracts and collaborations with research partners. Describe subcontract oversight activities to ensure adequate fiscal management and project timeliness. In this paragraph describe the minimum experience required by organizational representatives of HDIs or Universities of Technology to serve as subcontractors for financial engagement on the research project.  Describe the internal institutional plans and procedures to ensure that recipients will comply fully with all applicable U.S. Federal regulations, policies, and Guidelines for research involving vertebrate animals and human subjects, including for human subjects the evaluation of risks and protections in project proposals and appropriate ethical oversight of funded projects. 

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed with the following additional instructions:

In the budget justification section, applicants should demonstrate how the proposed budget will be distributed among the PD/PIs and collaborative partners.  Applicants are required to use the majority of funds to support work to be performed at the South African institution(s), with no less than fifty percent (50%) of the total budget costs directly supporting the South African component(s) of the research project. The 50% minimum applies to the entire project, not each budget year.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe the specific aims of the project and indicate how the specific aims will be accomplished by the PD/PIs and collaborators.

Research Strategy:

• Describe how the outcomes from the research project support the global health efforts to monitor, understand, treat, or prevent disease.
• Provide the scope of research conducted by each member of the research team and discuss how the PD/PIs and collaborators, and key personnel will be involved in the execution of the research.
• If applicable, provide a description of the research activities or experiences provided through the proposed research project(s) that will engage scientists from under-resourced institutions (HDIs and other South African Universities of Technology) that have a demonstrated commitment to biomedical research but have limited resources or experience, leading to the establishment or enhancement of research skills and expertise. Describe the specific role of the participating scientist in the proposed project and how their role contributes to the overall success of the proposed research.   
• Provide a plan for monitoring the day-to-day activities of the research and remediating any identified delays or setbacks in the implementation of the research project.
• Describe potential collaborations and involvement of community groups, local organizations, or other institutions in the research project.

Letters of Support: Applicants from the U.S. and South Africa must include a Letter of Support signed by the respective institutional official agreeing to provide institutional support for the proposed research project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. 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 Grants.gov

4. Submission Dates and Times

Part I. 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 Grants.gov (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 Grants.gov 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 Grants.gov 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply 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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will evaluate Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policies and practices, 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 will receive a written critique.

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.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.
• Geographic distribution of South African Institutions.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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. 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, 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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Brian Remortel, M.P.H.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4816
Email: [email protected] 

Geraldina Dominguez, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-920-6044 
Email: [email protected] 

Sonia Lee, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-4783
Email: [email protected] 

Christopher Gordon, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1613
Email: [email protected] 

Kendall Bryant, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0332
Email: [email protected] 

David Chang, Ph.D.
Office of AIDS Research (OAR)
Telephone: 301-827-4221
Email: [email protected] 

Dr Michelle Mulder Ph.D.
South African Medical Research Council
Telephone: +27 21 938 0937
Email: [email protected] 

Raul Rojas, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-0492
Email: [email protected] 

Annie Grimes
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7315
Email: [email protected] 

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: [email protected] 

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected] 

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]   

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]    

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.

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 2 CFR Part 200.