Foa_Content_of_RFA-PS-23-005 (extend due date).pdf

Centers for Disease Control and Prevention

NATIONAL CENTER FOR HIV, VIRAL HEPATITIS, STDS AND TB PREVENTION

Expanding Rapid Initiation of Antiretroviral Therapy in Non-traditional Settings: Emergency Department

RFA-PS-23-005

03/27/2023

Table of Contents 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

Overview

Participating Organization(s)

Centers for Disease Control and Prevention Components of Participating Organizations

Components of Participating Organizations:

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Notice of Funding Opportunity (NOFO) Title

Expanding Rapid Initiation of Antiretroviral Therapy in Non-traditional Settings: Emergency Department Activity Code

U01 - Research Project - Cooperative Agreement

Notice of Funding Opportunity Type

New Agency Notice of Funding Opportunity Number

RFA-PS-23-005

Assistance Listings Number(s)

93.084 Category of Funding Activity

HL - Health NOFO Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to support implementation research on the rapid or immediate initiation of HIV antiretroviral therapy (ART) for persons newly diagnosed with HIV or for persons with HIV (PWH) returning to care in emergency department (ED) settings. The rapid ART model, defined as immediate diagnosis, linkage to care, and ART initiation on the same day as a new HIV diagnosis or return to care, should offer an accelerated entry into HIV medical care. Rapid ART confers a higher rate of engagement in care, reduces the time to viral suppression, and improves morbidity and mortality in PWH. The ED offers a unique setting to immediately engage with patients who are not accessing HIV care services. The implementation research supported by this funding will deploy rapid ART models in ED settings and evaluate acceptability, perceived barriers and facilitators, feasibility, sustainability, and HIV care continuum outcomes. Applied research resulting from this funding is expected to decrease HIV infections and quickly achieve viral suppression among PWH. This research is aligned with the HIV National Strategic Plan (2022-2025) and the Ending the HIV Epidemic in the U.S. (EHE) initiative “Treat” Pillar.

Key Dates

Publication Date:

To receive notification of any changes to RFA-PS-23-005, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

02/21/2023 02/21/2023

Application Due Date:

03/27/2023 03/27/2023

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 11:59 PM U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

E-mail: commons@od.nih.gov Phone: 301-402-7469 or (toll-free) 1-866-504-9552 Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays https://www.grants.gov/ http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

05/24/2023 Secondary Review:

06/20/2023 Estimated Start Date:

09/30/2023 Expiration Date:

03/28/2023 Required Application Instructions

It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. 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.

Note:The Research Strategy component of the Research Plan is limited to 25 pages.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary

Purpose: The purpose of this Notice of Funding Opportunity (NOFO) is to support implementation research on the rapid or immediate initiation of HIV antiretroviral therapy (ART) for persons newly diagnosed with HIV or for persons with HIV (PWH) returning to care in emergency department (ED) settings. The rapid ART model, defined as immediate diagnosis, linkage to care, and ART initiation on the same day as a new HIV diagnosis or return to care, should offer an accelerated entry into HIV medical care.

Rapid ART confers a higher rate of engagement in care, reduces the time to viral suppression, and improves morbidity and mortality in PWH. The ED offers a unique setting to immediately engage with patients who are not accessing existing HIV services.

This NOFO supports research to result in increasing HIV testing for all adults, increasing usage of the rapid ART model, and removing barriers to HIV diagnosis and treatment in all care settings. The implementation research supported by this funding should deploy rapid ART models in ED settings and evaluate acceptability, perceived barriers and facilitators, feasibility, sustainability, and HIV care continuum outcomes. Applied https://grants.nih.gov/grants/how-to-apply-application-guide.html research resulting from this funding is expected to decrease HIV infections and quickly achieve viral suppression among PWH. This research is aligned with the HIV National Strategic Plan (2022-2025) and the Ending the HIV Epidemic in the U.S. (EHE) initiative “Treat” Pillar.

Mechanism of Support: U01 – Research Project - Cooperative Agreement Funds Available and Anticipated Number of Awards: The estimated total funding available, including direct and indirect costs, for the entire four (4)-year project period is $6,000,000. The estimated number of awards is three (3). Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded, and the number of awards will depend upon the number, quality, duration and cost of the applications received.

Budget and Project Period: The estimated total funding (direct and indirect) for the first year (12-month budget period) is $1,500,000 with individual awards ranging from $400,000 to $500,000 for the first year. The estimated total funding (direct and indirect) for the entire project period is $6,000,000. The project period is anticipated to run from 09/30/2023 to 09/29/2027.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. “Application and Submission Information” of this announcement.

Eligible Institutions/Organizations. Institutions/organizations listed in Section III. of this announcement are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

Number of PDs/PIs. There will only be one PD/PI for each application.

Number of Applications. Only one application per institution (normally identified by having a unique entity identifier [UEI] number) is allowed.

Application Type. New.

Application Materials. See Section IV.1 for application materials. Please note that

SF424 (R&R) FORMS-H is to be used when completing the application package. Please see https://grants.nih.gov/grants/how-to-apply-application-guide.html

Section I. Funding Opportunity Description

Statutory Authority Public Health Service Act, Sections 301(a) [42 USC 241(a)], 317(k)(2) [42 USC 247b(k)(2)], and 318 [42 USC 247c], as amended.

1. Background and Purpose

Immediate initiation of antiretroviral therapy (ART) is now recommended for anyone newly diagnosed with HIV, regardless of CD4 count. In the treatment as prevention paradigm, population-level viral load suppression is strongly associated with decreases in HIV incidence.

The rapid ART model, defined as immediate diagnosis, linkage to care, and ART initiation on the same day as a new HIV diagnosis or return to care, offers an accelerated entry into HIV medical care. Rapid ART reduces the time to viral suppression and improves morbidity and mortality in persons living with HIV. Initiating ART at the time of diagnosis, or soon afterwards, is now the standard of care in “traditional” care settings, based on its improved efficacy, safety, and acceptability.

Delays in initiating ART are associated with subsequent lower rates of viral suppression and retention in care, and with earlier development of first AIDS event. To achieve rapid ART, a person with a new HIV diagnosis needs to be immediately linked to care. Structural, personal or provider-related barriers may impede initiation of ART. Programs are underway to study and expand rapid ART in HIV clinics in the United States; however, patients from groups that have been economically or socially marginalized may not be accessing these programs. To achieve the Ending the HIV Epidemic’s (EHE) “Treat” Pillar goal of treating people with HIV rapidly and effectively to reach sustained viral suppression, expanding rapid ART initiation to novel settings may be needed.

The emergency department (ED) is a key venue where persons with undiagnosed HIV infection can be diagnosed and linked to care. The ED may be the only point of entry into the healthcare system for some PWH. However, diagnosis and linkage to care from EDs has, to date, been suboptimal, even for patients seen for concurrent STIs. The ED offers a unique setting to immediately engage with patients who may be missed in traditional care models.

Studies suggest the rapid ART model can be applied to a diverse range of clinical contexts. In ambulatory clinic settings, multi-site qualitative research has identified important elements associated with successful rapid ART program implementation. These include an implementation champion, comfort and competence in prescribing rapid ART, expedited access to ART medications, expertise in benefits, linkage, and care navigation, commitment to a patient-centered approach, and strong communication methods and culture. In the pre-rapid ART era, Los Angeles County and the University of Southern California's (LAC+USC) ED developed criteria for empiric ART for suspected cases of acute HIV utilizing HIV specialists. Of 16 cases of acute HIV infection, 11 met their criteria for empiric ART and agreed to treatment, suggesting feasibility and acceptability among patients in a small trial for clinical acute HIV infections.

This NOFO supports research to investigate how to deploy and optimize rapid ART delivery in EDs that are currently routinely screening for HIV infection. The research may incorporate lessons learned from the growing expertise of implementing rapid ART in other settings, the advancements in ART provision, and HIV testing technologies. The ED offers a unique and novel opportunity to immediately engage with newly diagnosed patients to initiate ART and provide linkage to an HIV provider in the community. The overarching purpose of the research is to enhance HIV screening, which may include implementing alternative HIV tests, and provide rapid ART initiation in the EDs. The project should utilize opt-out HIV testing in EDs and the novel strategy of providing rapid ART in EDs. This research may help determine whether HIV testing and rapid ART in EDs can improve engagement, linkage and retention in care, and viral suppression among newly diagnosed people with HIV (PWH), as well as those previously diagnosed with HIV but who are not engaged in care. Findings from this implementation research project may have the potential to decrease HIV infections through decreased time to viral suppression among PWH. This study is aligned with the HIV National Strategic Plan (2022-2025) and the Ending the HIV Epidemic in the U.S. (EHE) initiative “Treat” Pillar.

Relevant References:

1. U.S. Department of Health and Human Services. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. https://hivinfo.nih.gov/hiv-source/medical-practice-guidelines/hiv-treatment-guidelines/hiv-treatment-guidelines-adults-and

2. Solomon SS, Mehta SH, McFall AM, et al. Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a cross-sectional, comparative study. Lancet HIV.

2016;3(4):e183-e190. doi:10.1016/S2352-3018(16)00019-9.

3. Hansoti B, Mwinnyaa G, Hahn E, et al. Targeting the HIV Epidemic in South Africa:

The Need for Testing and Linkage to Care in Emergency Departments.

EClinicalMedicine. 2019;15:14-22. Published 2019 Aug 19.

doi:10.1016/j.eclinm.2019.08.007

4. Coffey S, Bacon O. Immediate ART Initiation & Restart: Guide for Clinicians. AETC National Coordinating Resource Center. 2021 Jun 10. Accessed September 2, 2021.

https://aidsetc.org/resource/immediate-art-initiation-restart-guide-clinicians

5. Koenig SP, Dorvil N, Dévieux JG, et al. Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial. PLoS Med. 2017;14(7):e1002357. Published 2017 Jul 25.

doi:10.1371/journal.pmed.1002357

6. Labhardt ND, Ringera I, Lejone TI, et al. Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing on Linkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The CASCADE Randomized Clinical Trial. JAMA. 2018;319(11):1103-1112. doi:10.1001/jama.2018.1818 https://hivinfo.nih.gov/hiv-source/medical-practice-guidelines/hiv-treatment-guidelines/hiv-treatment-guidelines-adults-and https://hivinfo.nih.gov/hiv-source/medical-practice-guidelines/hiv-treatment-guidelines/hiv-treatment-guidelines-adults-and https://aidsetc.org/resource/immediate-art-initiation-restart-guide-clinicians

7. Mateo-Urdiales A, Johnson S, Smith R, Nachega JB, Eshun-Wilson I. Rapid initiation of antiretroviral therapy for people living with HIV. Cochrane Database Syst Rev.

2019;6(6):CD012962. Published 2019 Jun 17. doi:10.1002/14651858.CD012962.pub2.

8. Pilcher CD, Ospina-Norvell C, Dasgupta A, et al. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting. J Acquir Immune Defic Syndr. 2017;74(1):44-51.

doi:10.1097/QAI.0000000000001134

9. Colasanti J, Sumitani J, Mehta CC, et al. Implementation of a Rapid Entry Program Decreases Time to Viral Suppression Among Vulnerable Persons Living With HIV in the Southern United States. Open Forum Infect Dis. 2018;5(6):ofy104. Published 2018 Jun

28. doi:10.1093/ofid/ofy104

10. Grabowski MK, Serwadda DM, Gray RH, et al. HIV Prevention Efforts and Incidence of HIV in Uganda. N Engl J Med. 2017;377(22):2154-2166. doi:10.1056/NEJMoa1702150

11. Dombrowski JC, Simoni JM, Katz DA, Golden MR. Barriers to HIV Care and Treatment Among Participants in a Public Health HIV Care Relinkage Program. AIDS Patient Care STDS. 2015;29(5):279-287. doi:10.1089/apc.2014.0346

12. HRSA. Health Resources and Services Administration. (2021). About the Ryan White HIV/AIDS Program, Part F: Special Projects of National Significance (SPNS) Program.

HIV/AIDS Bureau. https://hab.hrsa.gov/about-ryan-white-hivaids-program/about-ryan-white-hivaids-program

13. Kapadia SN, Singh HK, Jones S, Merrick S, Vaamonde CM. Missed Opportunities for HIV Testing of Patients Tested for Sexually Transmitted Infections at a Large Urban Health Care System From 2010 to 2015. Open Forum Infect Dis. 2018;5(7):ofy165.

Published 2018 Jul 19. doi:10.1093/ofid/ofy165

14. Amanda Hirsch, BA, Christopher F Carpenter, MD, MHSA, 954. Missed opportunities for HIV Screening in the Emergency Department, Open Forum Infectious Diseases, Volume 7, Issue Supplement_1, October 2020, Pages S508–S509, https://doi.org/10.1093/ofid/ofaa439.1140

15. Hoover KW, Huang YA, Tanner ML, et al. HIV Testing Trends at Visits to Physician Offices, Community Health Centers, and Emergency Departments — United States, https://hab.hrsa.gov/about-ryan-white-hivaids-program/about-ryan-white-hivaids-program https://hab.hrsa.gov/about-ryan-white-hivaids-program/about-ryan-white-hivaids-program https://doi.org/10.1093/ofid/ofaa439.1140

2009–2017. MMWR Morb Mortal Wkly Rep 2020;69:776–780. DOI:

http://dx.doi.org/10.15585/mmwr.mm6925a2

16. Koester KA, Moran L, LeTourneau N, et al. Essential elements of and challenges to rapid ART implementation: a qualitative study of three programs in the United States. BMC Infect Dis. 2022;22(1):316. doi:10.1186/s12879-022-07297-3

17. Jacobson KR, Arora S, Walsh KB, et al. High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department. J Acquir Immune Defic Syndr. 2016;72(3):242-245. doi:10.1097/QAI.0000000000001006

Health Equity:

CDC supports efforts to improve the health of populations disproportionately affected by infectious diseases by maximizing the health impact of public health services, reducing disease incidence, and advancing health equity.

A health disparity occurs when a health outcome is seen to a greater or lesser extent between populations. Health disparities in infectious diseases are inextricably linked to a complex blend of social determinants that influence which populations are most disproportionately affected by these infections and diseases.

Social determinants are conditions in the places where people live, learn, work, and play that affect a wide range of health and quality-of life-risks and outcomes (https://www.cdc.gov/socialdeterminants/index.htm). These include conditions for early childhood development; education, employment, and work; food security, health services, housing, income, and social exclusion. Health equity is a desirable goal that entails special efforts to improve the health of those who have experienced social or economic challenges. It requires:

Continuous efforts focused on elimination of health disparities, including disparities in health and in the living and working conditions that influence health, and

Continuous efforts to maintain a desired state of equity after health disparities are eliminated.

The application should use data, including social determinants data, to identify communities within their jurisdictions that are disproportionately affected by infectious diseases and related diseases and conditions, and plan activities to help eliminate health disparities. In collaboration with partners and appropriate sectors of the community, consideration should be given to social determinants of health in the development, implementation, and evaluation http://dx.doi.org/10.15585/mmwr.mm6925a2 https://www.cdc.gov/socialdeterminants/index.htm of specific efforts and use culturally appropriate interventions and strategies that are tailored for the communities for which they are intended.

Healthy People 2030 and other National Strategic Priorities

Healthy People 2030 Goals

HIV-1: Reduce the number of new HIV infections HIV-2: Increase knowledge of HIV status HIV-3: Reduce the number of new HIV diagnoses HIV-5: Increase viral suppression

National Goals

HIV National Strategic Plan (2022-2025) https://www.hiv.gov/federal-response/national-hiv-aids-strategy/national-hiv-aids-strategy-2022-2025 o Goal 1: Prevent new HIV infections 1.2: Increase knowledge of HIV status o Goal 2: Improve HIV-related health outcomes of people with HIV 2.1: Link people to care immediately after diagnosis and provide low-barrier access to HIV treatment 2.4: Increase the capacity of the public health, health care delivery systems, and health care workforce to effectively identify, diagnose, and provide holistic care and treatment for people with HIV o Goal 3: Reduce HIV-Related Disparities and Health Inequities 3.2: Reduce disparities in new HIV infections, in knowledge of status, and along the HIV care Continuum 3.4: Address social and structural determinants of health and co-occurring conditions that impede access to HIV services and exacerbate HIV-related disparities

Ending the HIV Epidemic in the U.S. https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview

Goal: Reducing new HIV infections by 75% by 2025 and 90% by 2030.

Public Health Impact

To achieve a 90% reduction in new HIV infections by 2030, people with HIV (PWH) will need to be diagnosed as early as possible and treated with ART rapidly and effectively to reach sustained viral suppression. Increasing the number of PWH rapidly initiated on ART, who adhere to ART, and achieve viral suppression, will help reduce new HIV infections in the United https://www.hiv.gov/federal-response/national-hiv-aids-strategy/national-hiv-aids-strategy-2022-2025 https://www.hiv.gov/federal-response/national-hiv-aids-strategy/national-hiv-aids-strategy-2022-2025 https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview

States and further the goals of Ending the HIV Epidemic (EHE) initiative in narrowing HIV-related health disparities. Educating healthcare providers and staff about rapid ART best practices and implementing rapid ART protocols may increase awareness and understanding of ART in patients newly diagnosed with HIV. Implementation research can increase understanding of the “real-world” acceptability and feasibility of rapid ART in hospital settings such as EDs, among patients, providers, and staff. The identification of barriers and facilitators to rapid ART initiation, use, and adherence should lead to the development of culturally competent, setting specific, training materials and workflow strategies for integrating rapid ART in emergency departments and other similar settings. Findings from the research supported by this NOFO may be used to support strengthening and expanding rapid ART across the United States and may inform future guidelines and recommendations to be incorporated into service delivery.

Rapid start of ART in the ED is an intervention that helps ensures all PWH can be started on ART at the time of diagnosis with potential cost benefit. Rapid ART should be accessible and immediate for all newly diagnosed PWH regardless of sociodemographic status. Rapid start also holds promise for engaging or re-engaging in care persons who were previously diagnosed with HIV but never entered or had disengaged from HIV care. The intervention may improve equity and greatly expand accessibility of ART for people who may not have access through traditional health care services. The research supported by this NOFO should include PWH in EHE jurisdictions disproportionately impacted by HIV. PWH should receive a timely HIV diagnosis, ensure that they are rapidly started on ART, and linked to care prior to discharge from the ED.

Results from this research may accelerate the progress along the HIV care continuum from diagnosis to linkage and ultimately to viral suppression.

Relevant Work

Published programmatic announcements related to Ending the HIV Epidemic in the United States, and the elimination of viral hepatitis in the United States, include:

PS19-1906: Strategic Partnerships and Planning to Support Ending the HIV Epidemic in the United States: https://www.grants.gov/web/grants/view-opportunity.html?oppId=316989

PS20-2010: Integrated HIV Programs for Health Departments to Support Ending the HIV Epidemic in the United States: https://www.grants.gov/web/grants/view-opportunity.html?oppId=32386

HRSA-20-113: Building Capacity to Implement Rapid Antiretroviral (ART) Initiation for Improved Care Engagement – Evaluation and Technical Assistance Provider:

https://www.hrsa.gov/grants/find-funding/hrsa-20-113

HRSA-20-114: Building Capacity to Implement Rapid Antiretroviral (ART) Initiation for Improved Care Engagement – Implementation Sites: https://www.hrsa.gov/grants/find-funding/hrsa-20-114

2. Approach https://www.grants.gov/web/grants/view-opportunity.html?oppId=316989 https://www.grants.gov/web/grants/view-opportunity.html?oppId=316989 https://www.grants.gov/web/grants/view-opportunity.html?oppId=323863 https://www.grants.gov/web/grants/view-opportunity.html?oppId=323863 https://www.hrsa.gov/grants/find-funding/hrsa-20-113 https://www.hrsa.gov/grants/find-funding/hrsa-20-114 https://www.hrsa.gov/grants/find-funding/hrsa-20-114

Logic Model: Expanding Rapid Initiation of Antiretroviral Therapy in Non-traditional Settings:

Emergency Department

Strategies & Activities

Short-term Outcomes

Intermediate-term Outcomes

Long-term Outcomes

Strategy 1:

Accurately and effectively diagnose new HIV infections or PWH returning to care in the emergency department.

Activity 1.1:

Provide and encourage an “opt-out” universal HIV testing strategy in the ED to all patients, utilizing point-of-care testing or other rapid diagnostics

Activity 1.2:

Establish collaboration between hospital laboratory and hospital emergency room to prioritize HIV testing and communication of positive tests to ED providers

S-T Outcome 1.1:

Increased identification of new diagnoses of HIV or PWH returning to care in ED settings

I-T Outcome 1.1.:

Increased availability of HIV testing for patients

I-T Outcome 1.2:

Improved notification of HIV testing results to provider/patient

Strategy 2:

Expand rapid ART initiation to patients on the same day as diagnosis or the same day PWH return to care in the ED, and conduct pre- & post- implementation clinical outcome monitoring Activity 2.1:

Develop and design an effective implementation study to facilitate rapid ART initiation in EDs

Activity 2.2:

Examine acceptability and barriers to implementation of

S-T Outcome 2.1:

Development of a combined HIV treatment and service practice model to scale up rapid ART

S-T Outcome 2.2:

I-T Outcome 2.1:

Improved capacity of EDs to provide rapid start with increased availability of & access to HIV treatment

I-T Outcome 2.2:

Increased knowledge of barriers and

L-T Outcome 1:

Increased number of people tested for HIV in the ED

L-T Outcome 2:

Increased viral suppression among PWH

L-T Outcome 3:

Decreased transmission of HIV from PWH and reduced new HIV infections

L-T Outcome 4:

Improved HIV-related health outcomes and overall quality of life for

PWH

L-T Outcome 5:

Reduced HIV-related health disparities and improved health equity

L-T Outcome 6:

Integrated and coordinated programming for testing for HIV and rapid ART rapid ART in the ED from both patient and staff perspectives

Activity 2.3:

Establish collaboration between ED site, community/affiliated HIV clinics/providers, and health department, to enhance pre-and post- implementation monitoring

Improved awareness and understanding of rapid ART by staff, clients, and patients

S-T Outcome 2.3:

Improved local stakeholder engagement and mobilization for rapid initiation of HIV treatment facilitators to rapid ART in ED settings

I-T Outcome 2.3:

Increased number of PWH rapidly initiated on ART

I-T Outcome 2.4:

Enhanced monitoring of HIV health outcomes in patients diagnosed from the ED or returning to care to the ED

Strategy 3:

Provide linkage to care services to patients initiated on ART in the ED.

Activity 3.1:

Implement a patient navigator model in the ED to assist with linkage to HIV care

Activity 3.2:

Establish collaboration and communication channels between ED and community/affiliated

HIV

clinics/specialist/health departments to ensure linkage to care

S-T Outcome 3.1:

Increased availability of linkage to care and other support services for

PWH

I-T Outcome 3.1:

Greater number of PWH initiating ART, linked to care, and retained in care over 6–12-month period

This NOFO supports research to compare the implementation of rapid initiation of ART with the standard of care HIV services conducted in at least three (3) ED sites located in high HIV prevalence communities, each partnering with their affiliated HIV clinics and specialists. The applicant should develop a study protocol that combines implementation and effectiveness outcomes, which should include acceptability, fidelity, and cost, in addition to clinical outcomes such as proportion of patients screening for HIV, initiated on rapid ART, retained in care, and who have achieved viral suppression. A pre-to-post comparison design may be considered to compare rapid ART deployment with the standard of care HIV services pre-rapid ART implementation. Pre-implementation data may be actively obtained during the first phase of the study or through retrospective review through electronic health record systems. Additional design alternatives may include randomization of individual ED sites to same day ART versus immediate referral to clinic and linkage to care.

The site should operate within, or be affiliated with, clinical facilities that have the infrastructure and staff for insurance/payor benefits navigation and ART medication initiation and administration. The application should describe collaborative partners, including pharmacy, clinic, and health department partnerships and rapid ART ED champions/leaders. In addition, the application should provide letters of support from the hospital or ED director/supervisor indicating willingness to participate. The application should also describe current organizational capacity and the capacity to implement rapid start of ART. The application should demonstrate adequate power for the proposed sample size. The research may be completed in two phases:

Phase 1:

The application should describe the development of the study protocol, instruments, and obtaining appropriate approvals. Recipients should conduct formative work, use evaluative and iterative strategies to assess rapid ART readiness in the ED, and use pilot evaluation data in order to define and then refine the intervention model. The application should demonstrate statistical power to achieve study goals for their proposed sample size. Consultation with and engagement of diverse sets of collaborators (e.g., outpatient HIV clinics/specialists, local and state public health departments, emergency departments, and hospital leadership) is encouraged. Program evaluation data relevant to the pre-implementation standard of care operations and potential post-implementation operations, staffing, and workflow should be assembled. Results from formative and assessment work should be used to design a rapid ART model and linkage to care model (i.e., patient navigator model) that can be integrated into the emergency departments. This phase may last up to 12 months.

Phase 2:

This phase may involve training project staff, fielding the study protocol, the intervention implementation, and data collection. An example workflow could be as follows: When HIV screening results are positive (whether through testing such as antibody, antigen, or nucleic acid amplification or confirmatory testing), the ED clinician is notified, who then notifies the “HIV Team”. The “HIV Team” may consist of a case manager/navigator to assist with linkage to care and appointments, a prescribing provider, and the ED Pharmacy. If an “HIV Team” member is not available, the ED provider can assume these roles, if able. The provider should follow a protocol and see the patient to discuss the new diagnosis of HIV, risks/benefits of treatment, and treatment initiation (either through a treatment starter pack or prescription sent to the pharmacy).

ART should be initiated as soon as possible following the protocol, including if the patient is admitted to the hospital. The ED Pharmacy may also be notified of the positive HIV result and be available for support. Follow-up and linkage to care may then be coordinated by the case manager/navigator with the partnering HIV clinic, where a patient may be anticipated to continue their HIV care post-ED/hospital release. The team may also be available for consultation via telehealth. Test results that may return after the patient is discharged, such as HIV genotype, should be sent to the partnering HIV clinic for follow-up.

Rapid ART training should be standardized across participating EDs, to the extent possible. The application should describe plans for training, roles and responsibilities, and desired competencies of staff. The recipient should create a data sharing partnership between the ED, the partnering HIV clinic, and/or health department. Enrollment in the study should be continuous over 2 years, or until enrollment goals are met. EHE jurisdictions should be prioritized, as these will have the highest expected participants. Participating patients should be followed for up to 12 months. Collaborating clinics and health departments may assist with providing data after the initial encounter. Baseline surveys/interviews and serial surveys of staff and patients should be considered to gather data relevant to evaluating project implementation and monitoring project outcomes (please see the Objectives/Outcomes section of this NOFO).

Objectives/Outcomes

This implementation study should address the following research questions:

1. Is ART initiation in the ED acceptable, feasible, and tolerable for patients, providers, patient navigators and other members of the care team (in the ED as well as in the clinic receiving referral)?

2. What are the challenges to implementing rapid ART in the ED setting?

Overall research objectives are to:

1. Enhance “opt-out” HIV testing strategies in the selected EDs and expand point of care HIV testing.

2. Implement rapid ART initiation (same day as HIV diagnosis or in PWH returning to care) in emergency ED settings.

3. Implement a patient navigator model in the ED to assist with linkage to HIV care.

4. Assess whether the above activities improve engagement and retention in care, linkage, and viral suppression among newly diagnosed PWH or those returning to care.

5. Analyze logistics and cost of implementing rapid ART initiation in emergency ED settings.

A complete list of outcomes and associated indicators should be finalized by recipients in the first 6-months post award. Study research variables, outcomes, and tools could include (but are not limited to):

Research Variable Assessed Study Sample(s)

Data Collection Tool(s)

Health Outcomes Primary: proportion of patients rapidly initiated on ART at diagnosis, linked to HIV medical care, retained in care, achieved viral

Patients Electronic Health Records (in the ED, and in the partnering HIV clinic) suppression.

Secondary: HIV screening rates and diagnostic yield, time to specific milestones such as time to ART initiation, viral suppression or first clinic appointment, treatment modification incidence.

Implementation Process Measures (strategies, adaptation, barriers, structural challenges, facilitators, fidelity)

Staff, Leadership

Survey, Interview

Implementation Context and Outcomes (reach, fidelity, appropriateness, acceptability, feasibility, adherence, and sustainability)

Staff, Leadership, Patients

Survey, Interview

Cost (labor and non-labor) Staff/Location Setting

Cost Questionnaires

Implementation process measures and outcomes (assessed through serial surveys and interviews with physicians, pharmacists, ED staff, and PWH (if possible):

Feasibility and acceptability by patients, pharmacists, and clinicians o Organizational/structural challenges to rapid ART initiation o Understanding and awareness of rapid ART o Examining refusal rates by PWH and reasons for refusal o Reach (number and proportion of individuals willing to participate in the intervention by staff and/or patients

Assessment of barriers to care o Insurance and payment structure

Health outcomes:

HIV screening rates in the ED (number of tests performed, percent positive, percent of new versus longstanding HIV diagnoses determined by patient report/health department surveillance, differences by demographics, and diagnostic yield)

Uptake of ART (proportion of eligible PWH offered ART who initiated the therapy, proportion of patients who refused ART, reasons for refusal, differences by demographics)

Linkage to HIV care clinic within 1, 3, 6 or 12 months Viral loads, CD4 count, achieving viral suppression (HIV VL<50 cp/mL) by 3, 6, or 12 months, durable viral suppression (i.e., two consecutive suppressed viral load results at least 3 months apart within 12 months)

Retention in care (i.e., 2 clinic and/or, telehealth visits with lab measurements at least 3 months apart within 12 months)

Time to specific milestones (to first clinic visit, to VL suppression) o From ED check in to HIV test, HIV result, test disclosure to patient o From positive result to clinic contact/referral, ART initiation (first prescription date, starter pack given), first clinic visit o From ART initiation to clinic visit, first refill date, first viral load suppression, missed appointment o Adherence (documented by self-report, pill count, pharmacy refills, or real-time electronic monitors)

Assessment of cost-effectiveness of intervention using cost data and savings o Cost questionnaires

Target Population

The target population for this research study includes all persons ≥ 18 years old with either newly diagnosed HIV or who have been previously diagnosed with HIV but are not engaged in care. Not engaged in care shall be defined as not having a clinic visit or HIV viral load test in the past 12 months and not currently taking or being prescribed ART. Populations may include, but are not limited to, American Indian or Alaska Native, Asian, Black/African American, Native Hawaiian or other Pacific Islanders, White, Hispanic/Latino, migrant populations, women, older people (65+), the general public, men who have sex with men, and/or persons who inject drugs.

Collaboration/Partnerships

The application should propose formal partnerships with emergency departments that are eligible to participate in this study (referred to in this NOFO as “participating EDs”). A participating ED is defined as an ED that agrees to partner with the recipient to implement study activities.

Memoranda of Agreement or Understanding (MOA/MOU), letters of commitment, or service agreements should be used to document proposed and current partnerships with participating clinics.

Guidelines for an MOU/MOA with Participating Clinics Applications should demonstrate that there is an MOU/MOA with all participating EDs and participating clinics signifying commitment to engage in the proposed study activities. Each MOU/MOA should be submitted with the application.

The purpose of each MOU/MOA is to set forth the responsibilities of the applicant and the participating clinic relative to the proposed goals of the project. The MOU/MOA should indicate a commitment of participation for the entire four-year project period.

Each MOU/MOA should include:

An effective date range that aligns with all four (4) years of the NOFO.

Acknowledgment that the clinic meets each of the participating clinic eligibility criteria stated in the NOFO.

Overview of the participating clinic’s plan and the estimated budget for implementing required study activities.

Agreement that the recipient will engage clinic representatives in relevant study-related meetings and processes, where appropriate, and that the clinic will participate accordingly.

Commitment of the recipient to work with the clinic and other collaborative partners to address project requirements, including the designation of a point of contact among the study team dedicated to the implementation of study activities.

Commitment of the clinic to either participate in, or assist recipient with, required data reporting and evaluation activities, including EMR data abstraction.

Signatures for both parties by authorized representatives, including the Principal Investigator or Emergency Department Director and the Clinic Director.

Applications should identify expected implementation research collaborators and established partnerships. The application should describe plans to collaborate with emergency departments that are performing universal opt-out HIV screening. Applications should describe operation of, or capability to provide, ART initiation and administration. The application should describe any experience of effective collaboration with ED/facility clinical providers and outpatient clinics or a strong potential to do so. The application should also establish state or local health department collaborators in selected jurisdictions who will have expertise in HIV surveillance in the state/local area selected.

Award recipients should establish memoranda of understanding, and data sharing and use agreements, as appropriate, to ensure rapid start program-related data are collected per protocol.

The recipient is expected to develop an effectiveness-implementation study protocol, manual of operations and tools, including refining and detailing the target study enrollment, objectives and outcomes, conduct the study and data analyses, and disseminate aggregated findings.

Evaluation/Performance Measurement

The application should include measurable goals and aims based on a four (4)-year research project period. The application should describe specific, measurable, achievable, realistic, and time-phased (SMART) project objectives for each activity described in the application’s project plan and describe the development and implementation of project performance measures based on specific programmatic objectives.

The evaluation plan should align with the stated purpose and outcomes described in the NOFO.

Applications should develop an implementation plan that includes a timeline to achieve study milestone and a staffing, recruitment, and enrollment plan. The evaluation plan should also describe the inclusion of relevant protocols, including human subjects research protocol development and approval, collaboration with CDC to develop and submit necessary Office of Management and Budget (OMB) protocols for OMB-PRA approval, as well as a quality assurance plan that ensures that the educational materials provided to patients and staff is accurate and up-to-date and that survey, focus group, and interview protocols are culturally appropriate and tailored for the people with HIV. The application should also describe the collection and summarization of background data on all participating emergency departments, including their location, HIV prevalence in the metropolitan statistical area, and HIV care and treatment continuum outcomes among PWH in that area.

The application should describe an evaluation plan including the following components:

Assessment of provider/staff knowledge, attitudes, and beliefs about rapid initiation of ART, and feasibility/acceptability of rapid ART in emergency departments using qualitative, quantitative, or mixed methods

Assessment of patient knowledge, attitudes, and beliefs about rapid initiation of ART and feasibility/acceptability of rapid ART in emergency departments using qualitative, quantitative, or mixed methods

Identification of barriers including organizational or structural challenges/ facilitators to expanding rapid ART initiation to emergency departments

Establishing collaborator interrelationships and roles, including identifying potential ED rapid ART project champions/leaders

Orientation and training of staff or partners in conducting opt-out HIV tests at all ED encounters

Orientation and training of staff or partners in initiating rapid ART in the ED Identification and training of clinic sites for linkage of HIV care Tailoring of an intervention to local context and participating sites Integration of rapid start of ART into routine ED workflow Equitable enrollment of eligible PWH by sex, age, and race/ethnicity Quantitative assessment of implementation, service, and patient objectives/outcomes described above Post-study assessment of provider and patient experiences with rapid ART Cost of the rapid start in the ED intervention at each site/location, including identifying resources, labor and non-labor costs

Rapid ART related patient evaluation measures:

Completion of participant surveys to ascertain behaviors, social determinants of health, attitudes around rapid ART, and adherence to ART

Number of patients screened for HIV Number of patients with positive HIV test Number of new HIV diagnoses versus previously diagnosed but not on treatment

(determined by patient report/health department surveillance) Number of patients initiated on rapid ART Number retained in care Number of patients virally suppressed

Translation Plan

The strategies to rapidly initiate ART in different care settings and increase opportunities for treatment initiation may be evaluated to identify best practices for rapid ART implementation in non-traditional settings, such as emergency departments. These best practices may be incorporated into guidelines and support materials and could also serve as the basis for future implementation studies that aim to scale-up and expand rapid ART in different settings. Key findings should be disseminated at national and international meetings and in peer-reviewed journals, as warranted.

Questions to consider in preparing this section of the application include:

How will successful activities of this implementation research be identified?

How will successful activities be incorporated into routine clinical practice?

How will this work guide scale-up of rapid ART use and delivery models in the United

States?

How will the research findings help promote or accelerate the dissemination, implementation, or diffusion of improvements in public health programs, hospitals, or practices?

How will findings advance or guide future research efforts or related activities?

3. Funding Strategy

N/A

Section II. Award Information

Funding Instrument Type:

CA (Cooperative Agreement) A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding:

$6,000,000

Estimated Total Annual Budget Period Funding, including direct and indirect costs:

Year 1: $1,500,000 Year 2: $1,500,000 Year 3: $1,500,000 Year 4: $1,500,000

Estimated total funding available for the first year (first 12 months), including direct and indirect costs: $1,500,000

Estimated total funding available for the entire project period, including direct and indirect costs: $6,000,000

Anticipated Number of Awards:

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling:

$500,000 Per Budget Period

Award Floor:

$400,000 Per Budget Period

Total Period of Performance Length:

4 year(s)

Throughout the Period of Performance, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

If you are successful and receive a Notice of Award, in accepting the award, you agree that the award and any activities thereunder are subject to all provisions of 45 CFR Part 75, 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.

Section III. Eligibility Information

1. Eligible Applicants

Eligibility Category:

00 (State governments)

01 (County governments)

02 (City or township governments) https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf

04 (Special district governments)

05 (Independent school districts)

06 (Public and State controlled institutions of higher education)

07 (Native American tribal governments (Federally recognized))

08 (Public housing authorities/Indian housing authorities)

11 (Native American tribal organizations (other than Federally recognized tribal governments))

12 (Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education)

13 (Nonprofits without…