RFA-PS-21-003.pdf

Centers for Disease Control and Prevention

National Center for HIV-AIDS, Viral Hepatitis, STD, and TB Prevention Extramural Research

Program Office

PrEP Choice: Increasing the Use of HIV Pre-exposure Prophylaxis in an Era of Choices

RFA-PS-21-003

Application Due Date: 01/05/2021

PrEP Choice: Increasing the Use of HIV Pre-exposure Prophylaxis in an Era of Choices

RFA-PS-21-003

TABLE OF CONTENTS

Part 1. Overview Information Key Dates Required Application Instructions Executive Summary

Part 2. Full Text Section I. Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 1. Overview Information

Participating Organization(s)

Centers for Disease Control and Prevention

Components of Participating Organizations

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Notice of Funding Opportunity (NOFO) Title

PrEP Choice: Increasing the Use of HIV Pre-exposure Prophylaxis in an Era of Choices

Activity Code

U01 – Research Project - Cooperative Agreement

Notice of Funding Opportunity Type

New

Agency Notice of Funding Opportunity Number

RFA-PS-21-003

Assistance Listings (CFDA) Number(s)

93.941 93.943

Category of Funding Activity:

Health

NOFO Purpose

Several HIV pre-exposure prophylaxis (PrEP) options are available to gay, bisexual, and other men who have sex with men (MSM). Three options that are currently available include daily oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC), daily oral tenofovir alafenamide and emtricitabine (TAF/FTC), and 2-2-1 dosing of TDF/FTC. A fourth option, bi-monthly injectable long-acting cabotegravir (CAB LA), is expected to become available in early 2022.

Evidence-based tools have been developed to assist healthcare providers with screening for PrEP indications, PrEP counseling, PrEP initiation, and to support adherent and persistent use of PrEP. Despite availability of these support tools, PrEP coverage among persons with PrEP indications remains low in the United States and racial/ethnic disparities in PrEP use persist.

Real-world uptake of clinical practice guidelines by providers is often delayed. Implementation of PrEP evidence-based tools and best practices is needed to increase the use of this effective HIV prevention intervention for MSM. In addition, information about PrEP use and factors influencing PrEP decisions among MSM – choice of regimen, adherence, persistence, change of regimen – can help inform future PrEP clinical guidelines and best practices.

The purpose of this Notice of Funding Opportunity (NOFO) is to: a) implement evidence-based provider and patient education and support tools in clinical settings to increase PrEP screening, counseling, initiation, adherence, and persistence by MSM and b) to understand reasons for selection of a PrEP formulation and switching patterns associated with the use of daily, 2-1-1, and injectable PrEP. The recipient should implement PrEP best practices as outlined in the most current CDC PrEP clinical guidelines. The recipient should also collect data to describe real-world PrEP use among MSM in an era of multiple PrEP options.

Key Dates

Publication Date: To receive notification of any changes to RFA-PS-21-003, 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: 11/30/2020

Application Due Date: 01/05/2021

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. Applications must be submitted using the Application Submission System & Interface for Submission Tracking (ASSIST) module which is a web-based service used for the preparation and submission of grant applications to CDC through Grants.gov. ASSIST provides the ability for applicants to prepare their applications online, and offers the applicant additional capabilities including the ability to preview the application image, validate the application against required business rules, and prepopulate data from an applicant organization's records, therefore identifying issues earlier in the application submission process.

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: 02/23/2021

Secondary Review: 03/29/2021

Estimated Start Date: 09/01/2021

Expiration Date: 01/06/2021 Due Dates for E.O. 12372: Due no later than 60 days after the application receipt date.

Required Application Instructions

**ELECTRONIC APPLICATION SUBMISSION VIA ASSIST IS PREFERRED**

It is recommended that applicants use ASSIST for the electronic preparation and submission of applications through Grants.gov to CDC. ASSIST is an alternative method to prepare and submit applications, and provides many features to facilitate the application submission process which improves data quality (e.g., pre-population of organization data, pre-submission validation of business rules, and preview of the application image used for review). Use of the

Grants.gov downloadable Adobe application packages and submission process will still be supported.

It is critical that applicants follow the instructions in the SF 424 (R&R) 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.

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

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

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

Executive Summary

Purpose: The purpose of this NOFO is to: a) implement evidence-based provider and patient education and support tools in clinical settings to increase screening for PrEP indications, PrEP counseling, PrEP initiation, and PrEP adherence and persistence by MSM and b) to understand PrEP use and reasons for selection of a PrEP formulation and switching patterns associated with the use of daily, 2-1-1, and injectable PrEP.

Implementation science methods should be used to evaluate the effectiveness of the provider education module and support tools. The recipient should also collect data to describe real-world PrEP use among MSM in an era of multiple PrEP options.

Mechanism of Support: U01 – Research Project - Cooperative Agreement Funds Available and Anticipated Number of Awards: The estimated total funds available, including direct and indirect costs, for the entire five (5)-year project period is $31,200,000. The number of awards is estimated to be up to 6. 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 $6,240,000 with individual awards estimated to range from $520,000 to $1,040,000 for the first year. The estimated total funding (direct and indirect) for the entire project period is $31,200,000. The project period is anticipated to run from 09/01/2021 to 08/31/2026.

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

Application Type. New.

Application Materials. See Section IV.1 for application materials. Please note that Form F is to be used when completing the application package.

Part 2. Full Text

Section I. Funding Opportunity Description

Statutory Authority

Public Health Service Act, Section 301(a) [42 USC 241(a)], as amended and Section 317(k)(2) [42 USC 247b(k)(2)], as amended.

1. Background and Purpose

The Ending the HIV Epidemic: A Plan for America (EHE) initiative includes a pillar to prevent new HIV infections using pre-exposure prophylaxis (PrEP). Populations of young men who have sex with men (MSM), especially young black/African American and Hispanic/Latino MSM, have the highest rates of HIV diagnoses in the United States. MSM in these populations are most in need of PrEP and are priority populations for PrEP implementation. Increasing PrEP use by these priority populations is an urgent HIV prevention need.

Several PrEP options are available to MSM. The first PrEP agent was approved by the Food and Drug Administration (FDA) in 2012 and consists of two oral antiretroviral drugs – tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) – taken daily to prevent acquisition of HIV.

TDF/FTC was recommended by CDC in 2014 for MSM, heterosexuals, and persons who inject drugs (PWID) at substantial risk of acquiring HIV. In 2018 only 21% of men with PrEP indications were prescribed PrEP. PrEP uptake has lagged significantly among persons in black/African American and Hispanic/Latino populations.

In 2015, the effectiveness of TDF/FTC using a 2-1-1 regimen was demonstrated in a clinical trial that enrolled MSM. The 2-1-1 PrEP dosing is an event-driven regimen that requires two pills 2 to 24 hours before sex, one pill 24 hours later, and one more pill 24 hours after that. The 2-1-1 dosing regimen has been recommended as a PrEP option for MSM by the World Health Organization and the International AIDS Society. A second daily oral PrEP agent, tenofovir alafenamide, and emtricitabine (TAF/FTC), was approved by the FDA in 2019 for persons at risk of acquiring HIV-1 by sexual exposures other than vaginal sex.

PrEP options are expected to further increase in the next few years. In addition to daily oral PrEP and 2-1-1 PrEP, an intramuscular injection with CAB LA that is administered every two months is expected to become available in the United States by 2022. A phase 3 clinical trial of CAB LA in MSM and transgender women was stopped early in May 2020 by its Data and Safety Monitoring Board with the recommendation to offer it to all trial participants because it was effective in preventing HIV acquisition; since then, it has been demonstrated to have superior efficacy compared to TDF/FTC. FDA approval of CAB LA is anticipated by late 2021.

Islatravir, a novel antiretroviral agent, is currently being studied in a phase 2 clinical trial as a once-monthly oral PrEP drug and might become available in the upcoming years. Islatravir formulated as a 4-year subcutaneous implant is also in development. In addition, other antiretroviral agents and delivery systems are in early development.

PrEP initiation, adherence, and persistence are lower in younger persons and persons of color.

Many barriers contribute to these disparities, including the cost of PrEP, lack of awareness of HIV risk or PrEP as a prevention option, lack of access to health care, stigma and mistrust of healthcare systems, and misconceptions about the safety of PrEP. Another key barrier to PrEP adherence and persistence is the difficulty young persons have with taking a daily pill. PrEP 2- 1-1 dosing and long-acting formulations increase options for PrEP that do not require taking a pill every day.

CAB LA can obviate the need for a daily pill and, when it is discontinued, detectable but sub-therapeutic drug levels persist for a year or longer. This period is known as the “cabotegravir tail” and HIV acquired during this time period could become resistant. To prevent acquiring cabotegravir-resistant HIV, persons with ongoing risk behaviors must use another PrEP drug while the cabotegravir levels wane. Therefore, supporting oral PrEP use during this tail period is important.

CDC prepares frequent updates of its PrEP clinical guidelines to keep healthcare providers informed of evidence-based PrEP care, yet uptake of guidelines by providers is often delayed.

Evidence-based tools have been developed to assist healthcare providers with screening for PrEP indications, PrEP counseling, PrEP initiation, and to support adherent and persistent use of PrEP. Despite availability of CDC guidelines and clinical support tools, PrEP coverage among persons with PrEP indications remains low in the United States and racial/ethnic disparities in PrEP use exist.

With new PrEP options becoming available, healthcare providers can benefit from education to increase their awareness of the choices available to patients and to guide the effective and safe use of these new PrEP options in accordance with CDC PrEP guidelines. In addition, implementation of tools to facilitate identification of patients with PrEP indications and to counsel them about PrEP can help providers initiate PrEP for all of their patients who need it.

PrEP patients who do not adhere to PrEP, or do not persist with PrEP for as long as they are at risk of acquiring HIV, need access to tools to support adherence and persistence to help them to optimize the prevention benefits of their chosen PrEP regimen.

In healthcare settings that serve primarily black/African American and/or Latino MSM, this NOFO will implement provider training on PrEP options and recommendations for PrEP care;

provider tools to identify patients with PrEP indications; provider counseling tools to inform MSM with PrEP indications about PrEP options and to guide them to make the best PrEP choice for their HIV prevention needs; and patient adherence and persistence support tools.

PrEP options are rapidly increasing and as the PrEP landscape continues to change, implementation of provider education and tools are needed. Real-world data about PrEP use is needed to inform future guidelines and tools. This study should enroll an MSM cohort of new or existing PrEP users to describe PrEP use, reasons for selection of a given PrEP formulation, and switching patterns associated with the use of daily, 2-1-1, and injectable PrEP.

References:

1. HIV.gov. Ending the HIV Epidemic: About Ending the HIV Epidemic: Plan for America: Overview. https://www.hiv.gov/federal-response/ending-the-hiv-epidemic /overview. Updated: July 2, 2020.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2018 (Updated);

vol.31. http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published May 2020.

3. Administration USFaD. FDA Approves First Drug for Reducing the Risk of Sexually Acquired HIV Infection. http://wwwfdagov/NewsEvents/Newsroom/PressAnnounceme nts/ucm312210htm.

4. Harris NS, Johnson AS, Huang YA, et al. Vital Signs: Status of Human Immunodeficiency Virus Testing, Viral Suppression, and HIV Preexposure Prophylaxis

— United States, 2013–2018. MMWR Morb Mortal Wkly Rep 2019;68:1117–1123.

5. Huang YA, Zhu W, Smith DK, Harris N, Hoover KW. HIV Preexposure Prophylaxis, by Race and Ethnicity - United States, 2014-2016. MMWR Morbidity and Mortality Weekly Report. 2018;67(41):1147-1150.

6. Molina JM, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec 3;373(23):2237-46.

7. World Health Organization. What’s the 2+1+1? Event-driven oral pre-exposure prophylaxis to prevent HIV for men who have sex with men: Update to WHO’s recommendation on oral PrEP. Geneva: World Health Organization; 2019. https://apps .who.int/iris/bitstream/handle/10665/325955/WHO-CDS-HIV-19.8-eng.pdf?ua=1

8. Sag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320(4):379–96.

9. Descovy (emtricitabine and tenofovir alafenamide) [Package insert]. Foster City, CA:

Gilead Sciences Inc.; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019 /208215s011lbl.pdfpdf icon

10. HIV Prevention Trials Network. HPTN 083 Study Demonstrates Superiority of Cabotegravir for the Prevention of HIV. Jul 2020. https://www.hptn.org/news-and-event s/press-releases/hptn-083-study-demonstrates-superiority-cabotegravir-prevention-hiv

11. Harris NS, Johnson AS, Huang YA, et al. Vital Signs: Status of Human Immunodeficiency Virus Testing, Viral Suppression, and HIV Preexposure Prophylaxis

— United States, 2013–2018. MMWR Morb Mortal Wkly Rep 2019;68:1117–1123.

12. Huang YA, Tao G, Smith DK, Hoover KW. Persistence with HIV Preexposure Prophylaxis in the United States, 2012-2017. Clin Infect Dis. 2020 doi:

10.1093/cid/ciaa037

13. Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, et al. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial. Lancet HIV.

2017;4(8):e331–40. pmid:28546090

Health Equity:

This program supports efforts to improve the health of populations disproportionately affected by HIV/AIDS, viral hepatitis, sexually transmitted infections (STIs) and tuberculosis (TB) by maximizing the health impact of public health services, reducing disease prevalence, and promoting health equity consistent with the National HIV/AIDS Strategy available at https ://www.whitehouse.gov/administration/eop/onap/nhas.

Health disparity is a particular type of health difference that is closely linked with social or economic disadvantage based on racial or ethnic group, religion, socioeconomic status, gender, mental health, cognitive, sensory, or physical disability, sexual orientation, geographic location, or other characteristics historically linked to discrimination or exclusion [HP 2020 - http://www .healthypeople.gov/2010/hp2020/advisory/PhaseI/glossary.htm]. Health disparities in HIV, viral hepatitis, STIs, and TB are inextricably linked to a complex blend of social determinants that influence which populations are most severely affected by these diseases.

Social determinants are the economic and social conditions that influence the health of individuals, communities and jurisdictions and 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 disadvantage. 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 particular health disparities are eliminated.

Programs should use data, including social determinants data, to identify communities within their jurisdiction that are disproportionately affected by HIV, viral hepatitis, STIs and TB and related diseases and conditions, and plan activities to help eliminate health disparities. In collaboration with partners and appropriate sectors of the community, programs should consider social determinants of health in the development, implementation, and evaluation of program specific efforts and use culturally appropriate interventions that are tailored for the communities for which they are intended.

Healthy People 2030 and other National Strategic Priorities

Healthy People goals related to reducing new HIV infections, increasing HIV testing, and increasing access to care for persons with HIV infection:

HIV-1: Reduce the number of new HIV diagnoses.

HIV-2: Reduce the number of new HIV infections among adolescents and adults.

HIV-6: Reduce new AIDS cases among adolescent and adult men who have sex with men.

HIV-9: Reduce the proportion of persons with a diagnosis of Stage 3 HIV (AIDS) within

3 months of diagnosis of HIV infection.

HIV-13: Increase the proportion of persons living with HIV who know their serostatus.

HIV-14: Increase the proportion of adolescents and adults who have been tested for HIV in the past 12 months.

o HIV-14.1: Increase the proportion of adolescents and adults who have ever been tested for HIV.

o HIV-14.2: Increase the proportion of men who have sex with men (MSM) who report having been tested for HIV in the past 12 months.

National Goals

Ending the HIV Epidemic: A Plan for America https://www.hiv.gov/federal-response /ending-the-hiv-epidemic/overview o Increase PrEP coverage 50% by 2025 Ratio of persons who have been prescribed PrEP to the number with indications for PrEP

Public Health Impact

Increasing the number of persons with PrEP indications who initiate, adhere to, and persist with PrEP will help to accomplish the goals of EHE. PrEP choices have been increasing with new drugs and formulations that will become available in the next few years, including the long-acting injectable PrEP drug CAB-LA. Educating healthcare providers about PrEP best practices, including recommended use of new PrEP drugs, will ensure the delivery of quality PrEP services in accordance with CDC guidelines, and increase the number of PrEP users. Evidence-based tools are available to support PrEP initiation and use but have been underutilized. These tools will be implemented to help healthcare providers screen patients for PrEP indications;

counsel them about PrEP choices and factors that are important in their choice of PrEP regimen;

guide their selection of a PrEP regimen; and support their adherence to, and persistence with, PrEP. Implementation science methods will be used to evaluate the effectiveness of the education module and support tools.

This research will also increase our understanding of provider and patient factors that influence the choice of a PrEP regimen; adherence and persistence with various regimens; changes in regimen; CAB LA tail coverage; sexually transmitted infections (STIs) while using PrEP; and the overall PrEP experience of providers and patients. Findings from this implementation study will be used to support expanded use of effective provider PrEP tools and increase understanding of PrEP use by MSM to inform the future revisions of CDC PrEP recommendations and interventions to increase PrEP use by persons in priority populations.

Relevant Work

PS18-1802: Integrated Human Immunodeficiency Virus (HIV) Surveillance and Prevention Programs for Health Departments https://www.cdc.gov/hiv/funding/announcements/ps18-1802 /guidance-relateds.html

PS20-2020: 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

PS15-1509: THRIVE Health Department Demonstration Projects for Comprehensive Prevention, Care, Behavioral Health, and Social Services for Men Who Have Sex with Men of Color at Risk for and Living with HIV Infection https://www.cdc.gov/hiv/research/thrive/about .html

PS15-1506: Project PrIDE https://www.cdc.gov/hiv/research/demonstration/projectpride.html

SHIPP Study: Sustainable Healthcenter Implementation PrEP Pilot (SHIPP) Study https://clini caltrials.gov/ct2/show/NCT02074891

2. Approach

To most effectively accomplish the goals of EHE, it is critical to implement quality PrEP services for persons in populations with the highest rates of HIV diagnoses, young MSM and especially black/African American and Hispanic/Latino MSM. The study should be conducted in communities with high rates of HIV diagnoses among black/African American and Hispanic/Latino MSM, and clinical venues in those communities that provide care for primarily black/African American and Hispanic/Latino populations including community health centers, STD clinics, PrEP clinics, and LGBT clinics.

The provider education component of this study should implement a scalable training module about available PrEP options using the most current CDC recommendations that should be piloted with providers. The module should include education on daily, 2-1-1, and long-acting injectable PrEP, and should be aligned to the most recent CDC PrEP guidelines. The impact of the training module should be assessed by a pre- and post-training test.

The PrEP tool component of this study should implement published, evidence-based tools in multiple clinical settings to support providers to assess patients for PrEP indications; counsel them about PrEP choices; guide their selection of a PrEP regimen; and support their adherence to and persistence with PrEP. Data from risk-matched historical controls should be used to evaluate the effectiveness of the implementation of these tools. In addition, quantitative and qualitative methods such as provider and patient surveys, interviews, and focus groups should be used to understand the implementation of these tools

Both new and existing PrEP patients should be eligible for the study. Providers should assess all MSM aged 18-39 years for PrEP indications; counsel them about PrEP options of daily oral PrEP, 2-1-1 PrEP, or CAB LA; and offer PrEP.

Study visits should coincide with quarterly or more frequent clinical PrEP care visits. PrEP users should be monitored for the duration of the study to assess their PrEP use, including selection of an initial (new users) or alternate (existing users) PrEP regimen; reasons for selecting the PrEP regimen; PrEP adherence, persistence, and any change of regimen; and CAB LA tail coverage if CAB LA is discontinued. All PrEP patients should receive high-quality, standard-of-care adherence and persistence counseling and support at each clinic visit. PrEP users in whom suboptimal adherence is identified should be provided additional tools to support their adherence. Implementation of enhanced adherence support tools should be evaluated using pre- and post-implementation data for that person. Providers should also conduct ongoing assessments of PrEP need, and persistence tools should be implemented for those who need help deciding to continue PrEP and to persist with PrEP for as long as needed.

The study should enroll new and existing PrEP patients and collect data to describe:

Selection of a PrEP regimen o Self-report o Electronic health records (EHRs) o Pharmacy records

Adherence to PrEP with implementation of enhanced adherence tools for persons with challenges o Self-report o Electronic medication monitoring (EMM) devices for daily or 2-1-1 PrEP o Laboratory testing for tenofovir-based PrEP regimens o EHRs o Pharmacy records

Persistence with PrEP with implementation of persistence tools for persons with challenges o Self-report o EHRs o Pharmacy records

Switching among PrEP regimens o Self-report o Electronic health records (EHRs) o Pharmacy records

Use of oral PrEP when discontinuing CAB LA o Self-reported adherence and persistence o EMM devices for daily or 2-1-1 PrEP for tail coverage o Laboratory testing for tenofovir-based PrEP regimens o EHRs o Pharmacy records

Sexual and injection drug behavior while using PrEP o Type of sexual behavior o Injection drug behavior o HIV status of partner o PrEP dosing o Condom use o STI testing and positivity

Objectives/Outcomes

The purpose of this NOFO is to: a) implement provider education and evidence-based support tools to increase PrEP screening, counseling, initiation, adherence, and persistence by MSM, and b) to understand PrEP use, reasons for selection of a PrEP formulation, and switching patterns associated with the use of daily, 2-1-1, and injectable PrEP. The recipient should implement PrEP best-practices as outlined in the most recent CDC PrEP clinical guidelines.

Implementation science methods should be used to evaluate the effectiveness of the education module and support tools. The recipient should also collect data to describe real-world PrEP use among MSM using PrEP in an era of multiple PrEP options.

Whenever possible, applications should include objectives written in the SMART format (e.g., Specific, Measurable, Achievable, Realistic and Time-bound).

Research objectives are to:

Increase PrEP providers’ knowledge of PrEP drugs and recommendations for their use Assess the implementation of published, evidence-based tools for PrEP screening, initiation, and adherence and persistence support Increase the number of MSM who initiate PrEP Increase the percentage of MSM taking PrEP who have medication adherence adequate for HIV prevention Increase the percentage of MSM taking PrEP who persist with PrEP for as long as risk of HIV acquisition exists Increase the percentage of MSM who discontinue CAB LA who maintain oral PrEP tail coverage for the clinically recommended duration Understand facilitators and barriers to maintaining the recommended tail coverage with oral PrEP after discontinuing CAB LA Understand factors that influence PrEP regimen selection, changes, and discontinuation

Target Population

Black/African American and Hispanic/Latino MSM who utilize healthcare services in clinical settings and the healthcare providers who work in these settings.

Collaboration/Partnerships

The application should describe plans to collaborate with multiple clinics that provide HIV prevention services, including PrEP, for a patient population that serves primarily black/African American and/or Hispanic/Latino MSM. The application should describe past experience of effective collaboration with clinical providers or a strong potential to do so.

Evaluation/Performance Measurement

The application should include measurable goals and aims based on a five (5)-year research project period. The application should include 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.

Implementation of provider education and published, evidence-based tools:

Quantitative assessment of provider knowledge pre- and post-education module Quantitative and qualitative assessment of healthcare provider attitudes and experience with the education module Quantitative and qualitative assessments of provider and patient attitudes and experience with PrEP support tools and PrEP use

PrEP use cohort:

Oral PrEP regimens

Quarterly assessment of adherence at study visits o Self-report of sexual encounters and PrEP use o Self-report of PrEP refills o Pill counts at each study visit o Laboratory testing for drug levels o Adherence and persistence interventions provided

Ongoing collection of EMM device data Monitoring of EHR and pharmacy data to assess PrEP persistence Weekly submission of email or text questionnaires (i.e., diaries) to report sexual encounters, dates and times of PrEP use, condom use, and STI diagnoses

CAB-LA

Monitoring of EHR and pharmacy data to assess PrEP persistence When discontinuing CAB-LA o Quarterly assessment of adherence at study visits Self-report of sexual encounters and PrEP use Self-report of PrEP refills Pill counts at each study visit Laboratory testing for drug levels Adherence and persistence interventions provided o Ongoing collection of EMM device data o Weekly submission of email or text questionnaires (i.e., diaries) to report sexual encounters, dates and times of PrEP use, condom use, and STI diagnoses

PrEP regimen changes

Quarterly assessment of adherence at study visits o Self-report of sexual encounters and PrEP use o Self-report of PrEP refills o Pill counts at each study visit o Laboratory testing for drug levels

Ongoing collection of EMM device data Monitoring of EHR and pharmacy data to assess PrEP persistence Weekly submission of email or text questionnaires (i.e., diaries) to report sexual encounters, dates and times of PrEP use, condom use, STI diagnoses, and PrEP regimen changes

PI’s of funded applications must submit an annual progress report showing project activities and outcomes based on the overall research goals and timeline. For more information on required Reporting, please see Section VI. of this NOFO.

Translation Plan

The effectiveness of PrEP tools to increase screening for PrEP indications, PrEP initiation, PrEP adherence, and PrEP persistence among MSM in priority populations of black/African American and Hispanic/Latino MSM will be evaluated to identify best practices for PrEP implementation in an era of multiple PrEP options. These best practices will be incorporated in CDC PrEP guidelines and support materials and will also serve as the basis for future implementation studies that aim to scale-up and expand the use of these PrEP implementation tools. CDC and the recipient will collaborate to disseminate key findings at national and international meetings and in peer-review journals, as warranted.

Questions to consider in preparing this section 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 successful PrEP service models in the United States?

Section II. Award Information

Funding Instrument Type: 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: $31,200,000 Estimated total funding available for the first year (first 12-month budget period), including direct and indirect costs: $6,240,000

Estimated total funding available for the entire five (5)-year project period, including direct and indirect costs: $31,200,000

Anticipated Number of Awards: 6

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

Award ceiling and floor are for the first 12-month budget period only.

Award Ceiling: $1,040,000 Per Budget Period Award Floor: $520,000 Per Budget Period Total Period of Performance Length: 5 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 (http://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.

Section III. Eligibility Information

1. Eligible Applicants

Eligibility Category: State governments County governments City or township governments Special district governments Independent school districts Public and State controlled institutions of higher education Native American tribal governments (Federally recognized) Public housing authorities/Indian housing authorities Native American tribal organizations (other than Federally recognized tribal governments) Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education Private institutions of higher education For profit organizations other than small businesses Small businesses

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

Nonprofits (Other than Institutions of Higher Education):

Nonprofits (Other than Institutions of Higher Education)

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

N/A

4. Justification for Less than Maximum Competition

N/A

5. Responsiveness

If an applicant requests a funding amount greater than the ceiling of $1,040,000 as indicated in Section II. of this NOFO, HHS/CDC will consider the application non-responsive and it will not enter into the review process. HHS/CDC will notify the applicant that the application did not meet the submission requirements.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://cage.dla.mil/ System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/index.html .

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing Principle Investigator (PD/PI) eRA Commons account is affiliated with the eRA commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the eRA Commons registration process at least four (4) weeks prior to the application due date. ASSIST requires that applicant users have active eRA Commons account in order to prepare an application. It also requires that the applicant organization's Signing Official have an active eRA Commons Signing Official account in order to initiate the submission process. During the submission process, ASSIST will prompt the Signing Official to enter their Grants.gov Authorized Organizational Representative (AOR) credentials in order to complete the submission, therefore the applicant organization must ensure that their Grants.gov AOR credentials are active.

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM). Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the recipient organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the recipient organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for

HHS/CDC support.

9. Cost Sharing

This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement, (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf), applications received in response to the same Notice of Funding Opportunity generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this NOFO that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

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

Section IV. Application and Submission Information

1. Address to Request Application Package In order to use ASSIST, applicants must visit https://public.era.nih.gov/assist where you can login using your eRA Commons credentials, and enter the Notice of Funding Opportunity Number to initiate the application, and begin the application preparation process.

If you experience problems 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:

· E-mail: http://grants.nih.gov/support/index.html

· Phone: 301-402-7469 or (toll-free) 1-866-504-9552. The NIH eRA Service desk is available Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding federal holidays.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF-424 (R&R) Application Guide http://grants.nih.gov/grants/how-to-apply-application-guide.htm and here: https://grants.nih.gov/grants/how-to-apply-application-guide/forms-f/general-forms-f.pdf, except where instructed in this Notice of Funding Opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review. The package associated with this NOFO includes all applicable mandatory and optional forms.

Please note that some forms marked optional in the application package are required for submission of applications for this NOFO. Follow the instructions in the SF-424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

When using ASSIST, all mandatory forms will appear as separate tabs at the top of the Application Information screen; applicants may add optional forms available for the NOFO by selecting the Add Optional Form button in the left navigation panel.

Letters of Support from partners or other organizations should be placed in the PHS 398 Research Plan "Other Research Plan Section" of the application under "9. Letters of Support".

Please include all of the eight (8) mandatory forms listed below in the application package:

Mandatory

1. SF424(R&R)[V2.0];

2. PHS 398 Cover Page Supplement [V4.0];

3. Research and Related Other Project Information [V1.4];

4. Project/Performance Site Location(s) [V2.0];

5. Research and Related Senior/Key Person Profile (Expanded) [V2.0];

6. Research and Related Budget [V1.4];

7. PHS 398 Research Plan [V4.0];

8. PHS Human Subjects and Clinical Trials Information [V1.0].

If multiple collaborating institutions will be involved, please include in this section of the application your single IRB (sIRB) Plan:

Describe how you will comply with the single IRB review requirement under the Revised Common Rule at 45 CFR 46.114 (b) (cooperative research). If available, provide the name of the IRB that you anticipate will serve as the sIRB of record.

Indicate that all identified engaged institutions or participating sites will agree to rely on the proposed sIRB and that any institutions or sites added after award will rely on the sIRB.

Briefly describe how communication between institutions and the sIRB will be handled.

Indicate that all engaged institutions or participating sites will, prior to initiating the study, sign an authorization/reliance agreement that will clarify the roles and responsibilities of the sIRB and participating sites.

Indicate which institution or entity will maintain records of the authorization/reliance agreements and of the communication plan.

Note: Do not include the authorization/reliance agreement(s) or the communication plan(s) documents in your application.

Note: If you anticipate research involving human subjects but cannot describe the study at the time of application, include information regarding how the study will comply with the single Institutional Review Board (sIRB) requirement prior to initiating any multi-site study in the delayed onset study justification.

Please include the one (1) optional form listed below, if applicable, in the application package:

Optional

1. R&R Subaward Budget Attachment(s) Form 5 YR 30 ATT.

3. Letter of Intent

Due Date for Letter of Intent: 11/30/2020 Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows CIO staff to estimate the potential review workload and plan the review.

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

Name of the applicant institution

Descriptive title of proposed research

Name, address, and telephone number of the PD(s)/PI(s)

Names of other key personnel

Participating institutions

Number and title of this notice of funding opportunity

The letter of intent should be sent to:

Gregory Anderson, MPH, MS

Extramural Research Program Office

Office of the Associate Director of Science

National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention

Centers for Disease Control and Prevention

U.S. Department of…