RFA-PS-22-001 Final.pdf

Centers for Disease Control and Prevention

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

Implementing Pre-exposure Prophylaxis for HIV Prevention in Syringe Service Programs

RFA-PS-22-001

01/18/2022

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 Implementing Pre-exposure Prophylaxis for HIV Prevention in Syringe Service Programs Activity Code U01 – Research Project - Cooperative Agreement

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-PS-22-001

Assistance Listings Number(s) 93.084,93.941 Category of Funding Activity HL - Health NOFO Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to support implementation research on combining HIV pre-exposure prophylaxis (PrEP) navigation and services at syringe services programs (SSP) for people who inject drugs (PWID). CDC is interested in increasing PrEP care through SSPs by incorporating enhanced PrEP navigation for PWID into standard processes. The NOFO seeks to support implementation research with effectiveness outcomes on the acceptability and feasibility of an enhanced PrEP navigation intervention at SSPs and optimizing it for linkage to, initiation of, and retention in PrEP care among adult PWID. Applied research resulting from this funding is expected to strengthen combined, integrated HIV prevention for PWID, and is aligned with the HIV National Strategic Plan (2021-2025) and the Ending the HIV Epidemic in the U.S. (EHE) initiative “Prevent” Pillar.

Key Dates Publication Date:

To receive notification of any changes to RFA-PS-22-001, 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:

12/17/2021 12/17/2021

Application Due Date:

01/18/2022 01/18/2022

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 5:00 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.

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:

03/17/2022 Secondary Review:

04/19/2022 Estimated Start Date:

09/30/2022 Expiration Date:

01/19/2022

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 15 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 combining pre-exposure prophylaxis (PrEP) at syringe services programs (SSP) for people who inject drugs (PWID) by designing and delivering an enhanced PrEP navigation intervention to increase initiation of, adherence to, and persistence of PrEP among PWID utilizing SSPs. CDC is interested in increasing PrEP care through SSPs by incorporating enhanced PrEP navigation into standard processes.

This NOFO seeks to support implementation research on the acceptability and feasibility of an enhanced PrEP navigation intervention at SSPs and optimizing it for linkage to, initiation of, and retention in PrEP care among adult PWID.

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 $2,500,000. The number of awards is estimated to be one (1). Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of meritorious applications.

Budget and Project Period: The estimated total funding (direct and indirect) for the first year (12-month budget period) is $625,000. The estimated total funding (direct and indirect) for the entire project period is $2,500,000. The project period is anticipated to run from 09/30/2022 to 09/29/2026.

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 DUNS number) is allowed.

Application Type. New.

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

SF424 (R&R) Form F 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, Section 301(a) [42 USC 241(a)] and Section 317(k)(2)[42 USC 247b(k)(2)], as amended.

1. Background and Purpose People who inject drugs (PWID) are a diverse population disproportionately affected by HIV in the United States. Using data triangulation, the CDC estimated there were about 770,000 PWID in the United States in 2011. A more recent national estimate for active PWID in the U.S. is not available, but the number is likely increasing based on the documented increases in rates of acute hepatitis C cases coincident with the opioid crisis in recent years.

During 2010-2014, the estimated lifetime risk of HIV diagnosis was approximately 2 to 4-fold higher among PWID compared with the general US population (about 1%). From 2015 to 2019, the percentage of HIV diagnoses attributed to non-sterile injection drug use increased and, in 2019, PWID accounted for about 1 in 15 new HIV diagnoses in the United States. The emergence of multiple HIV clusters among PWID during the opioid use crisis revealed prevention gaps and highlighted the need for wider implementation of effective biomedical HIV prevention strategies for PWID. PWID is a priority population in the HIV National Strategic Plan: A Roadmap to End the Epidemic for the United States (2021-2025).

Pre-exposure prophylaxis (PrEP), when taken daily, decreases the risk of acquiring HIV sexually by 99% and decreases the risk of acquiring HIV through injection drug use by at least 74%.

Despite this, PrEP continues to be underutilized in the U.S. Nationally, only 9.7% of females and 26.5% of males with indications for PrEP were prescribed PrEP in 2019. In 2015, CDC estimated 73,000 PWID had indications for PrEP use (PrEP indications include: non-prescribed injection drug use and sharing any injection or drug preparation equipment in the past 6 months and/or risk of sexual acquisition). In the 2018 National HIV Behavioral Surveillance PWID cycle, about 60% of HIV-negative PWID shared syringes or injection equipment, about 53% obtained syringes from SSPs, and only 1% took any PrEP in the past 12 months.

Studies indicate that PWID at risk of HIV report an interest in and willingness to use daily oral PrEP when available and accessible, but PrEP uptake has remained low in this population. In addition to low levels of awareness of PrEP, other barriers to access and use among PWID include stigma of taking PrEP and using drugs, misconceptions of this prevention modality among providers and patients, and lack of engagement with, or access to, health services in general. The anticipated FDA approval of long-acting injectable PrEP (cabotegravir LA) in 2021 and the robust investigative pipeline of other PrEP modalities (e.g., islatravir monthly oral or annual implants, lenacapavir injection every 6-12 months) will expand PrEP options for people at risk of HIV, including PWID, who may prefer a modality that does not rely on daily pill use.

SSPs already engage PWID by providing a range of ongoing services, including syringe exchange, comprehensive harm reduction, HIV and hepatitis C testing, and linkage to infectious disease treatment and care, as well as behavioral, psychosocial, and other essential services. Co-locating PrEP services with other prevention services at SSP sites, including fixed and mobile (i.e., outreach vans or pop-up) sites, may further reduce some barriers for access and increase uptake and persistence in PrEP among PWID.

Peer-based navigation has proven effective to link people with an HIV diagnosis to care and has been similarly used by health departments and community partners to link individuals who test negative for HIV, particularly men who have sex with men, to PrEP. Peers with shared experiences and backgrounds are often seen as reliable and non-judgmental and can help establish and build trust in communities. However, implementation strategies for peer-navigation to PrEP for PWID, including in SSP settings, have been little studied. Implementation research can aid in understanding barriers and facilitators to PrEP access and use by PWID, and to identify successful models for delivery of PrEP for this population, in order to increase the uptake of, and persistence in, PrEP care; and, in turn, reduce new HIV diagnoses in this priority population. Hybrid effectiveness-implementation study designs offer an opportunity to study both effectiveness and implementation outcomes within the same study and to encourage uptake of evidence-based interventions more quickly into public health practice.

The purpose and overarching goal of this NOFO is to support implementation research aiming to combine HIV prevention modalities for PWID at risk of HIV infection by incorporating enhanced PrEP services, including peer and other forms of navigation, at SSPs. Implementation research resulting from this project has the potential to decrease HIV infections among PWID and is aligned with the HIV National Strategic Plan (2021-2025) and the Ending the HIV Epidemic in the U.S. (EHE) initiative “Prevent” Pillar.

References:

1. Lansky A, et al. Estimating the number of persons who inject drugs in the United States by meta-analysis to calculate national rates of HIV and hepatitis C virus infections. PLoS One. 2014 May 19;9(5):e97596.

2. Hess KL, et al. Lifetime risk of a diagnosis of HIV infection in the United States. Ann Epidemiol. 2017;27(4): 238-243. doi:10.1016/j.annepidem.2017.02.003.

3. Ryerson AB, Schillie S, Barker LK, Kupronis BA, Wester C. Vital Signs: Newly Reported Acute and Chronic Hepatitis C Cases ― United States, 2009–2018. MMWR Morb Mortal Wkly Rep 2020;69:399–404.

DOI: http://dx.doi.org/10.15585/mmwr.mm6914a2.

4. Centers for Disease Control and Prevention. HIV Surveillance Report, 2019; vol. 32.

http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published May 2021.

Accessed May 27, 2021.

5. Lyss SB, et al. Responding to Outbreaks of Human Immunodeficiency Virus Among Persons Who Inject Drugs-United States, 2016-2019: Perspectives on Recent Experience and Lessons Learned. J Infect Dis. 2020 Sep 2;222(Suppl 5):S239-S249. doi:

10.1093/infdis/jiaa112.

6. Centers for Disease Control and Prevention. Effectiveness of Prevention Strategies to Reduce the Risk of Acquiring or Transmitting HIV.

https://www.cdc.gov/hiv/risk/estimates/preventionstrategies.html. Last updated November 12, 2019. Accessed June 7, 2021.

7. Centers for Disease Control and Prevention. PrEP.

https://www.cdc.gov/hiv/basics/prep.html. Last updated September 18, 2020. Accessed September 30, 2020.

8. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf. Published March 2018.

9. Centers for Disease Control and Prevention. HIV prevention pill not reaching most Americans who could benefit – especially people of color. Press Release.

https://www.cdc.gov/nchhstp/newsroom/2018/croi-2018-PrEP-press-release.html. Last updated March 6, 2018. Accessed September 30, 2020.

10. Centers for Disease Control and Prevention. HIV Infection Risk, Prevention, and Testing Behaviors among Persons Who Inject Drugs—National HIV Behavioral Surveillance:

Injection Drug Use, 23 U.S. Cities, 2018. HIV Surveillance Special Report 24.

http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published February 2020.

Accessed December 2020.

11. Stein M, et al. Willingness to use HIV pre-exposure prophylaxis among opiate users.

AIDS Behav. 2014;18(9):1694–700.

12. Walters SM, et al. Awareness of pre-exposure prophylaxis (PrEP) among women who inject drugs in NYC: the importance of networks and syringe exchange programs for HIV prevention. Harm Reduct J. 2017;14(1):40.

13. Kuo I, et al. Willingness to use HIV pre-exposure prophylaxis among community-recruited, older people who inject drugs in Washington, DC. Drug Alcohol Depend.

2016;164:8–13.

14. Sherman SG, et al. PrEP awareness, eligibility, and interest among people who inject drugs in Baltimore, Maryland. Drug Alcohol Depend. 2019;195:148–55.

15. Jo Y, et al. Interest in linkage to PrEP among people who inject drugs accessing syringe services; Miami, Florida. PLoS ONE. 2020;15(4): e0231424.

https://doi.org/10.1371/journal.pone.0231424

16. Roth AM, et al. An exploration of factors impacting preexposure prophylaxis eligibility and access among syringe exchange users. Sexually Transmitted Diseases. 2018; 45(4):

217-221.

17. Mayer KH, et al. Evolving models and ongoing challenges for HIV pre-exposure prophylaxis implementation in the United States. J Acquir Immune Deficienc Syndr.

2018; 77(2):119.

18. AIDS United. Best practices for integrating peer navigators into HIV models of care.

2015. https://ciswh.org/resources/best-practices-integrating-peer-navigators-hiv-models-care/

19. Blackstock OJ, et al. A pilot study to evaluate a novel pre-exposure prophylaxis peer outreach and navigation intervention for women at high risk for HIV infection. AIDS Behav. 2020; https://link.springer.com/article/10.1007/s10461-020-02979-y.

20. Biello KB, Mimiaga MJ, Valente PK, Saxena N, Bazzi AR. The Past, Present, and Future of PrEP implementation Among People Who Use Drugs. Curr HIV/AIDS Rep. 2021 Apr

27. doi: 10.1007/s11904-021-00556-z.

21. Landes, SJ, et al. An introduction to effectiveness-implementation hybrid designs.

Psychiatry Res. 2019; DOI: 10.1016/j.psychres.2019.112513.

22. Brown, CH, et al. An overview of research and evaluation designs for dissemination and implementation. Annu Rev Public Health. 2017; DOI: 10.1146/annurev-publhealth- 031816-044215.

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.

Applicants 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, applicants should consider social determinants of health in the development, implementation, and evaluation 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

National Goals

HIV National Strategic Plan (2021-2025) https://files.hiv.gov/s3fs-public/HIV- National-Strategic-Plan-2021-2025.pdf o Goal 1: Prevent New HIV Infections 1.3: Expand and improve implementation of effective prevention interventions, including treatment as prevention, PrEP, PEP and SSPs, and develop new options.

Ending the HIV Epidemic in the U.S. https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview o Goal 1: Prevent New HIV Infections Increase PrEP coverage to 50% by 2025 Reduce new HIV diagnoses by 75% by 2025 Reduce new HIV infections by 75% by 2025 o Goal 4: Achieve Integrated, Coordinated Efforts That Address the HIV Epidemic among All Partners and Stakeholders Identify, evaluate, and scale up best practices including through translational, implementation, and communication science research

Public Health Impact Increasing the number of PWID who initiate, adhere to, and persist on PrEP will help reduce new HIV infections in the United States and further the goals of EHE in narrowing HIV-related health disparities. PrEP, whereas proven effective at preventing new HIV infections when taken daily, is still largely underutilized, especially among PWID. There is currently scant evidence and models on how to best deliver and scale up the provision of PrEP for PWID in the United States. Peer navigation and other forms of navigation have been effective in other populations, and for linkages to service, and have the potential to increase uptake and persistence in PrEP among PWID if effectively and appropriately tailored for this population and for PrEP. Enhancing standard PrEP navigation and retention protocols by building peer support for PrEP into standard SSP operations holds promise for boosting the provision of PrEP in SSP settings and could be one approach to increase PrEP uptake among PWID.

Implementation research should increase understanding of the “real-world” acceptability and effectiveness of PrEP service delivery models, including peer-enhanced service delivery, for PWID. The identification of barriers/facilitators to PrEP initiation and adherence among PWID and their health care providers should lead to the development of culturally competent training materials and workflow strategies for integrating PrEP support in SSP settings. These materials and strategies should lead to increasing knowledge of PrEP, destigmatizing PrEP for PWID, increasing empowerment/self-efficacy to prescribe and take PrEP, and increasing trust between clients, peers, and providers. Findings from this multi-site implementation research study should be used to support strengthening and expanding PrEP implementation for PWID utilizing SSPs across the United States and should inform future CDC and partner programming for this priority population.

Relevant Work The proposed research should build upon existing research efforts by the CDC and partners to develop combined HIV interventions for priority populations and scale up implementation across the United States.

The following published programmatic annoucements are related to Ending the HIV Epidemic in the United States and the elimination of viral hepatitis in the United States:

RFA-PS-19-1906: Strategic Partnerships and Planning to Support Ending the HIV Epidemic in the United States.

https://www.cdc.gov/hiv/funding/announcements/ps19-1906/index.html

RFA-PS-20-2010: Integrated HIV Programs for Health Departments to Support Ending the HIV Epidemic in the United States.

https://www.cdc.gov/hiv/funding/announcements/ps20-2010/index.html

RFA-PS-21-2103: Integrated Viral Hepatitis Surveillance and Prevention Funding for Health Departments.

https://www.cdc.gov/hepatitis/policy/FO-CDC-RFA-PS21-2103.htm

RFA-PS-19-1909: National Harm Reduction Technical Assistance and Syringe Services Program (SSP) Monitoring and Evaluation Funding Opportunity.

https://www.cdc.gov/nchhstp/funding/announcements/ps19-1909/index.html

The following is a related research announcement on implementation science research:

RFA-PS-21-002: Implementation Research Consortium to Accelerate Impact of Health Department-Delivered HIV Prevention Activities.

https://www.grants.gov/web/grants/view-opportunity.html?oppId=328318

For common components and services provided with an SSP and SSP implementation see:

HIV and Injection Drug Use: Syringe Services Programs for HIV Prevention. (2016).

CDC Vital Signs. https://www.cdc.gov/vitalsigns/hiv-drug-use/index.html and https://www.cdc.gov/ssp/syringe-services-programs-summary.html#ssp-implementation

2. Approach

LOGIC MODEL: Summarizes the strategies and intended outcomes of the proposed research

Strategies and Activities

Short-Term Outcomes

Intermediate Outcomes

Long-Term outcomes

Recipient will design a multisite effectiveness-implementation study with the goal of improving acceptability of, and uptake and persistence of, PrEP among PWID at SSPs.

Recipient will implement a multi-site research protocol with an intervention, including peer enhanced PWID PrEP service provision at SSP study sites.

Recipient will conduct data analyses, dissemination, and translation of findings and lessons learned to programmatic activities for Ending the HIV Epidemic in the U.S.

with technical assistance from CDC.

Improved local stakeholder engagement and mobilization for combined HIV prevention in PWID to include PrEP.

Deployment of the peer enhanced PWID PrEP intervention package at SSP sites.

Integration of trained peer navigators into SSP workflow to support PrEP uptake and adherence among

PWID.

Improved capacity of SSPs to engage clients in PrEP care.

Increased awareness and understanding of PrEP by SSP staff and clients.

Increased knowledge of barriers and facilitators to PrEP for PWID at SSPs.

Increased HIV testing and linkage to HIV care for HIV infection.

Greater number of PWID initiating PrEP, adhering to PrEP, and persisting on PrEP over 6-12 month period.

Experience gained, lessons learned, and successful completion of an implementation science research project.

Development of a combined HIV prevention and service practice model for scale up of PrEP among PWID.

Reduced HIV infections in populations disproportionately affected by HIV.

Reduced HIV-related health disparities.

Integrated and coordinated programming for prevention of HIV and other infectious complications of injection drug use.

Improved health equity.

This NOFO will support a recipient to conduct a research study to implement a model of integrating PrEP with other SSP services, including syringe exchange, comprehensive harm reduction, HIV and hepatitis C testing, and linkage to infectious disease treatment and care, as well as behavioral, psychosocial, and other essential services, with a focus on enhanced PrEP navigation, including peer PrEP navigation. The application should describe study sites which may include SSPs across the urban and rural U.S. (e.g., see NASEN’s directory for reference: https://www.nasen.org/map/). The involvement of multiple and distinct SSPs (proposed range 3 to 5 sites) that vary in service delivery type (e.g., fixed location and mobile), program size, geography, and demographics of clients is encouraged.

The recipient should develop a study protocol that combines implementation and effectiveness outcomes. The recipient should develop and implement an enhanced PrEP navigation model at SSPs (intervention condition) and compare its outcomes with pre-intervention data at these SSPs (control condition). It is expected that the new enhanced PrEP navigation intervention may be integrated into the existing harm reduction and prevention services and workflows at the SSPs (please see https://www.cdc.gov/hiv/effective-interventions/prevent/prep/index.html). The proposed PrEP intervention may include other evidence-informed and evidence-based strategies designed to initiate and maintain PWID on PrEP, such as telehealth, system changes, site mobilization, insurance navigation, adherence support, standard PrEP information materials, counseling, and existing referrals, in addition to a focus on peer PrEP navigation.

The study should identify and engage multiple SSPs that do not have a formal or standardized PrEP navigation program in place. The application should present a plan to recruit, enroll, and follow PWID who do not have HIV infection but have indications for PrEP use (injection drug use and/or sexual behavior). The SSPs should operate within, or be affiliated with, clinical facilities that have the infrastructure and staff for insurance/payor benefits navigation and to prescribe PrEP and provide PrEP care. The application should describe collaborative partners, current organizational capacity, HIV prevention service operations at SSPs, and the capacity to implement an enhanced PWID PrEP navigation model.

Applicants may consider a stepped wedge cluster-randomized study design, which permits delivery of the intervention at all SSP sites, with a delayed intervention phase at some sites. This design has been used in evaluation of effectiveness components of interventions in real-world settings and is well suited for studies of practice-based improvements. (Please refer to implementation research references 21 and 22 in the Background and Purpose section above for illustrative designs). Intended study outcomes are described in more detail below and would include implementation outcomes such as acceptability of enhanced PrEP navigation intervention to SSP clients and providers, fidelity in implementing the intervention (and barriers and facilitators to it) along with effectiveness outcomes such as initiation of and persistence with PrEP among eligible PWID.

The award recipient should collect and manage all necessary study data elements in a manner that allows for combined analyses of outcomes across multiple SSP sites. Data should be de-identified and shared securely. CDC scientists will provide technical assistance on all analyses, interpretation, and results dissemination, as warranted.

Phase 1

The application should describe the development of the formative and project Phase 2 implementation study protocols and instruments and describe how all appropriate IRB approvals will be obtained. In Phase 1, the award recipient may conduct formative work and use evaluative and iterative strategies to conduct a site assessment for readiness for PrEP intervention and use pilot programmatic evaluation data to define the intervention model. Consultation with and engagement of diverse sets of stakeholders (e.g., community-based organizations, local public health authorities, leadership of clinical centers providing PrEP) is encouraged. The award recipient should assemble existing program evaluation data relevant to standard of care operations, staffing, and workflow at each SSP. Results from formative and site assessment work should be used to design an enhanced PrEP navigation model which includes peer navigation that can be integrated into workflow at participating SSPs.

Phase 2

This phase will involve training project staff, fielding the study protocol, and data collection.

Sites will identify PWID with indications for PrEP use. Study enrollment with informed consent will continue until a sufficient sample size of PWID participants for assessment of intervention effectiveness is reached.

The enhanced PrEP navigation intervention should complement existing routine SSP processes, which are expected to include services such as: HIV, STI, and viral hepatitis testing, standard PrEP information materials, counseling, and existing referrals or non-peer navigation to PrEP care and other essential services (e.g., housing, primary healthcare, medications for opioid use disorder [MOUD], etc.). Please refer to: https://www.cdc.gov/hiv/effective-interventions/prevent/prep/index.html. PrEP medications should be provided through insurance coverage (private or Medicaid), HHS’ Ready, Set, PrEP program, and/or private or state PrEP assistance programs, without any expenditure of CDC grant funds.

The enhanced PrEP navigation and training should be standardized across participating SSPs, to the extent possible, and should include ongoing support and navigation with PWID clients throughout the study duration. The application should describe plans for training, roles and responsibilities, and desired competencies of peer navigators, and present a conceptual model for how peers will aid study participants to begin PrEP and remain in PrEP care.

Baseline participant surveys should collect demographic, risk behavior, and other health-related data. The study follow-up should cover a minimum of 6 months of observation during the enhanced PrEP navigation intervention phase at each SSP. Data collected during participant follow-up visits will include risk behaviors, attitudes around PrEP, adherence to PrEP for those who start PrEP, and type of PrEP medication received. Adherence to PrEP will be measured by participant self-report, by pill counts, and by laboratory methods.

Phase 3

At the conclusion of the intervention phase, the awardee should collect data from PWID participants, peer navigators, and other key stakeholders at SSPs regarding the feasibility, acceptability, and fidelity of intervention, and assess program costs.

The award recipient should conduct all qualitative and quantitative analyses of study data, with technical assistance from CDC, as warranted. Overall project findings should be disseminated in various forums and used to inform future EHE programming and translation of findings for routine implementation.

Objectives/Outcomes This implementation study should address the following research gap and question: “How to design and deliver an enhanced PWID PrEP service bundle to increase initiation of, adherence to, and persistence of PrEP among PWID utilizing SSPs?”

Overall research objectives are to:

Test the feasibility, acceptability, and effectiveness of implementing a PrEP intervention service bundle to increase uptake of and persistence with PrEP among PWID clients of SSPs.

Assess barriers/facilitators to PrEP initiation among PWID at mobile and fixed care locations with SSPs. Tailor strategies to support PrEP initiation and persistence using peer navigators integrated into SSP workflow.

Evaluate retention in PrEP care among PWID SSP clients over time.

Assess costs of the peer enhanced PWID PrEP service bundle and compare with the cost of the existing PrEP referral or provision model.

Primary outcome: Percentage of study participants initiating PrEP before and after the introduction of a peer-enhanced PrEP navigation intervention for PWID.

Implementation objectives/outcomes could include (but are not limited to):

Develop an integrated workflow for peers to support PrEP uptake and care at SSPs Increase percent of PWID patients screened for PrEP eligibility and referred for PrEP care Increase percent of eligible PWID patients who receive a PrEP prescription and are linked to PrEP care Increase percent of PrEP patients who receive a PrEP prescription refill Increase percent of PrEP patients with follow up HIV/STI test done as part of PrEP care Increase SSP providers’ and PrEP providers’ knowledge of PrEP modalities and recommendations for their use for PWID as part of an intervention service bundle Monitor and increase the acceptability of the intervention to SSP clients, providers, and other stakeholders Assess the fidelity of implementation of the intervention bundle (including systematic adoption, PrEP offers, engagement of participants with peer navigators, etc.)

Monitor and quantify costs related to PrEP services and navigation before and after the introduction of the intervention service bundle

Service objectives/outcomes:

Monitor and minimize time from study enrollment to linkage with a peer navigator for the peer enhanced PWID PrEP service intervention bundle

Monitor and reduce time from study enrollment to receipt of PrEP prescription Monitor client-identified barriers and implement appropriate strategies to facilitate initiation of and persistence on PrEP Evaluate models of directly observed PrEP administration at the SSP (optional) Obtain diverse enrollment among eligible PWID clients by age, gender, and race/ethnicity

Client/Patient objectives/outcomes:

Increase percent of PWID SSP clients who fill their first PrEP prescription Increase percent of PWID SSP clients who refill their PrEP prescription Increase adherence to PrEP (self-report and objective measures) Reduce the number of new HIV infections Increase the percent of clients retained in SSP and other programs (such as substance use disorder treatment)

Target Population The target population for this research is people who inject drugs (PWID) ≥18 years old, who report injection drug use in the past 12 months, use SSPs, are HIV-negative, and have indications for PrEP use based on injection drug use or sexual behavior criteria.

Applications should present a plan to enroll a sufficiently sized and diverse population of PWID who use SSPs, with representation by age, sex, and race/ethnicity reflective of the broader population of clients at the site.

Collaboration/Partnerships Applications should identify expected implementation research collaborators and established partnerships. Applications should describe operation of, or affiliation with, SSPs for participant recruitment and PrEP intervention implementation. Applications should also describe partnerships with clinics that provide PrEP care and summarize past experiences of effective collaboration with such clinical providers, if available.

Involvement of, and collaborations with, local community-based organizations (CBOs) that serve PWID is highly encouraged. Award recipients should establish memoranda of understanding and data sharing and use agreements, as appropriate, to ensure SSP program-related and PrEP care-related data are collected per protocol and available for harmonized cross-site analyses. Working relationships with behavioral health clinics, substance abuse treatment clinics, and other clinical service providers may be beneficial in providing services to persons in need of PrEP.

Partnerships and collaboratives with local and state health departments are also encouraged to strengthen the research-to-practice feedback loop for implementing combined HIV prevention for PWID.

The award recipient is expected to develop a multi-site 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 with technical assistance from CDC, as warranted.

Applicants may refer to PrEP delivery models in developing their research plans:

https://www.cdc.gov/hiv/effective-interventions/prevent/prep/index.html

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 be in line with the implementation research logic model framework presented in the application.

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

Qualitative assessment of provider and HIV-negative PWID knowledge, attitudes, and beliefs about PrEP and feasibility/acceptability of a peer-enhanced PWID PrEP bundle intervention

Identification of barriers/facilitators to PrEP initiation and persistence Establishing stakeholder interrelationships and roles Orientation and training of SSP providers or partners in administering a PrEP program Identification and training of peer navigators Ongoing support for clinicians and peer navigators Engagement of PWID clients Tailoring of an intervention to local context at participating SSP study sites Integration of peer navigation into routine PrEP care workflow (change infrastructure) Tracking of the fidelity to the peer navigation intervention (clients matched to a peer navigator, weekly/monthly contacts/contact attempts with clients) Equitable enrollment of eligible PWID clients, by sex, age, and race/ethnicity Assessment of clients successfully completing health insurance/coverage navigation

(including timeliness) Quantitative assessment of implementation, service, and patient objectives/outcomes described above Post-study qualitative assessment of provider and patient experiences with PrEP use and peer navigation Timeliness (time to matching clients to peers, to PrEP prescription, to prescription filled) Costs of the peer enhanced PWID PrEP intervention bundle and costs of pre-intervention

PrEP referral or provision model at the SSPs.

PWID PrEP-related evaluation measures:

Number screened for PrEP indications Number receiving initial PrEP clinical evaluation

Documentation of the date and type (oral vs. other modality) of the initial PrEP prescription based on PrEP provider reporting or review of patient medical records, and assessment of PrEP adherence at study visits (discuss all applicable) o Self-report of PrEP use o Self-report of PrEP refills o Pill counts at each study visit o Directly observed PrEP administration (optional) o Laboratory testing for tenofovir concentration levels in plasma (optional) o Adherence and persistence interventions provided at the site

Monitoring of PrEP initiation and persistence (prescriptions filled/refilled) by using electronic health records and pharmacy data

Completion of participant surveys to ascertain risk behaviors, social determinants of health, attitudes around PrEP, and adherence to PrEP

Number, types, and results of HIV/STI tests Number of new HIV infections Number retained in SSP/substance treatment programs Number, types, and results of HCV tests

Translation Plan The strategies for, and the effectiveness of, the peer enhanced PWID PrEP service bundle to increase PrEP screening, linkage, prescription, initiation, adherence, and persistence at SSPs should be evaluated to identify best practices for PrEP implementation for this priority population. These best practices should be incorporated in PrEP guidelines and support materials and should also serve as the basis for future implementation studies that aim to scale-up and expand the use of these PrEP implementation tools. The award recipient should disseminate key findings at community meetings, national and international scientific meetings and in peer-reviewed journals with technical assistance from CDC, as warranted. Partnering with local and health department stakeholders involved in HIV prevention and PWID services is encouraged from the onset of the project to inform data collection, aid the research-to-practice cycle, and maximize the likelihood of translation of the intervention into a routine program, if feasible, acceptable, and effective.

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 integrated PrEP and SSP service 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 or practices?

How will the 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:

$2,500,000

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

Year 1: $625,000 Year 2: $625,000 Year 3: $625,000 Year 4: $625,000

Estimated total funding available for the first year (first 12 months), including direct and indirect costs: $625,000

Estimated total funding available for the entire project period of performance, including direct and indirect costs: $2,500,000

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:

$625,000 Per Budget Period

Award Floor:

$500,000 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)

04 (Special district governments)

02 (City or township 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 501(c)(3) status with the IRS, other than institutions of higher education)

20 (Private institutions of higher education)

22 (For profit organizations other than small businesses)

23 (Small businesses)

25 (Others (see text field entitled "Additional Information on Eligibility" for clarification))

Additional Eligibility Category:

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

Hispanic-serving Institutions

Historically Black Colleges and Universities (HBCUs)

Tribally Controlled Colleges and Universities (TCCUs)

Alaska Native and Native Hawaiian Serving Institutions

Governments:

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other:

Faith-based or Community-based Organizations

Regional Organizations

Bona Fide Agents: A Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms."

Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency's existing in-house or contractor resources. FFRDC's enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to https://gov.ecfr.io/cgi-bin/searchECFR.

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Additional Information on Eligibility The following types of Higher Education Institutions are always encouraged to apply for

CDC support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions

Nonprofits (Other than Institutions of Higher Education) Eligible Agencies of the Federal Government Faith-based or Community-based Organizations U.S. Territory or Possession Regional Organizations Bona Fide Agents: A Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms" when submitting via https://www.grants.gov

Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency’s existing in-house or contractor resources. FFRDC’s enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to https://gov.ecfr.io/cgi-bin/searchECFR

4. Justification for Less than Maximum Competition N/A

5. Responsiveness If an application requests a funding amount greater than the ceiling of $625,000, including direct and indirect costs, as indicated in Section II.