PS15-001 Amendment 1.pdf

Centers for Disease Control and Prevention

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Extramural Research Program Office

Positive Health Check Evaluation Trial

RFA-PS-15-001

Application Due Date: 03/16/2015

Positive Health Check Evaluation Trial

RFA-PS-15-001

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 Extramural Research Program Office (NCHHSTP ERPO) National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) Funding Opportunity Announcement (FOA) Title Positive Health Check Evaluation Trial Activity Code U18

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-PS-15-001

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.941 Category of Funding Activity:

Health FOA Purpose HIV antiretroviral therapy (ART) can durably suppress the plasma HIV-1 viral load which improves individual survival and dramatically reduces further HIV transmission. Achieving HIV viral suppression is a primary goal when initiating ART. Unfortunately, there are gaps throughout the continuum of HIV care in the United States and research shows only 25% of all people living with HIV (PLWH) know they are infected, get regular medical care, take ART, and achieve HIV viral suppression. Recent studies show that computer-based interventions are effective in improving protective health behaviors including ART adherence and sexual risk reduction among PLWH. In response to the need for more comprehensive and feasible interventions, CDC has developed Positive Health Check, a brief, web-based video counseling intervention to improve clinical health outcomes for PLWH including ART initiation, ART adherence as measured by suppressed HIV-1 viral load, retention in care, and sexual risk reduction as measured by incident STDs. The intervention is to be used by English-speaking PLWH in HIV primary care to supplement existing clinical care services. The Positive Health Check Evaluation Trial will evaluate this intervention.

The study will be conducted in three or four diverse HIV primary care clinics in the United States, and the trial will include a minimum of 2,320 eligible participants (1,160 per study arm). Electronic medical records, laboratory reporting data, medical charts, and appointment records will be used to determine patient eligibility for the study. PLWH eligible and enrolled in the trial will be randomized to either the intervention arm (i.e., Positive Health Check plus standard clinical care) or to the control arm (i.e., standard clinical care only). The Positive Health Check Evaluation Trial tests whether the intervention significantly improves persons’ clinical outcomes, including ART initiation, ART adherence as measured by suppressed HIV-1 viral load, retention in care, and sexual risk reduction as measured by incident STDs. The trial will also document the cost and feasibility of implementing and integrating the Positive Health Check intervention in diverse HIV primary care clinic settings in the United States.

NOTE: A Summary of the Conference Call held on Tuesday, January 13, 2015 with Potential Applicants for Funding Opportunity Announcement (FOA): PS15-001 “Positive Health Check

Applicants for Funding Opportunity Announcement (FOA): PS15-001 “Positive Health Check Evaluation Trial” and Answers to Questions from Potential Applicants has been added as an amendment to the FOA in Section VIII. "Other Information" on pages 44-45.

Key Dates Publication Date: To receive notification of any changes to RFA-PS-15-001, 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: 02/16/2015

Application Due Date: 03/16/2015

On-time submission requires that electronic applications be error-free and made available to CDC for processing from eRA Commons on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov/eRA Commons no later than 5:00 PM U.S. Eastern Time. Note:

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

Scientific Merit Review: 05/07/2015

Secondary Review: 06/12/2015

Estimated Start Date: 09/01/2015

Expiration Date: 03/17/2015 Due Dates for E.O. 12372: Executive Order 12372 does not apply to this program.

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

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.

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

Executive Summary Purpose: HIV antiretroviral therapy (ART) can durably suppress the plasma HIV-1 viral load which improves individual survival and dramatically reduces further HIV transmission. Achieving HIV viral suppression is a primary goal when initiating ART. Unfortunately, there are gaps throughout the continuum of HIV care in the United States and research shows only 25% of all people living with HIV (PLWH) know they are infected, get regular medical care, take ART, and achieve HIV viral suppression. Recent studies show that computer-based interventions are effective in improving protective health behaviors including ART adherence and sexual risk reduction among PLWH. In response to the need for more comprehensive and feasible interventions, CDC has developed Positive Health Check, a brief web-based video counseling intervention to improve clinical health outcomes for PLWH including ART initiation, ART adherence as measured by suppressed HIV-1 viral load, retention in care, and sexual risk reduction as measured by incident STDs. The intervention is to be used by English-speaking PLWH in HIV primary care to supplement existing clinical care services. The grantee will conduct the Positive Health Check Evaluation Trial and http://www.grants.gov http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf evaluate the study intervention in eligible PLWH from three or four diverse HIV primary care clinics in the United States. The grantee will enroll a minimum of 2,320 eligible participants (1,160 per study arm) in the study trial, with a minimum of 580 to a maximum of 1,160 enrolled per clinic. Electronic medical records, laboratory reporting data, medical charts, and appointment records from participating clinics will be used to determine patient eligibility for the study. PLWH who are eligible and enrolled in the trial will be randomized to either the intervention arm (i.e., Positive Health Check plus standard clinical care) or to the control arm (i.e., standard clinical care only). The Positive Health Check Evaluation Trial tests whether the intervention significantly improves persons’ clinical outcomes, including ART initiation, ART adherence (measured by suppressed HIV-1 viral load), retention in care, and sexual risk reduction (measured by incident STDs). The trial will also document the current standard of care for each collaborating clinic and the cost and feasibility of implementing and integrating the Positive Health Check intervention in diverse HIV primary care clinic settings in the United States.

Mechanism of Support. Cooperative Agreement Funds Available and Anticipated Number of Awards. Estimated total funding available, to include direct and indirect costs for the entire project period, is $2,900,000. The project period will be four years. There will be one award. The award issued under this FOA is contingent upon availability of funds, the total number of meritorious applications 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) will be $300,000. The estimated total funding (direct and indirect) for the second year (12-month budget period) will be $1,100,000, for the third year (12-month budget period) will be $1,000,000, and for the fourth year (12-month budget period) will be $500,000. The estimated total funding (direct and indirect) for the entire project period will be $2,900,000. The project period will run from 09/01/2015 to 08/31/2019.

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.1. of this funding opportunity 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 this project.

Number of Applications. Each eligible applicant institution may submit only one application.

Application Type. New Special Date(s). A potential applicant conference call will be held on Tuesday, January 13, 2015 from 10:00 am to 11:00 am Eastern Time. The bridgeline is: 1-866-662-8986; passcode:

8378091.

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

http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY:

(770) 488-2783.

Part 2. Full Text

Section I. Funding Opportunity Description

Statutory Authority

Sections 301 and 318 of the Public Health Service Act (42 U.S.C. Sections 241 and 247(c), as amended.

1. Background and Purpose

CDC announces the availability of fiscal year (FY) 2015 funds for a cooperative agreement program called the Positive Health Check Evaluation Trial. The randomized trial will evaluate the efficacy of Positive Health Check, a brief web-based video counseling intervention, developed by CDC to improve clinical health outcomes among English-speaking persons living with HIV (PLWH) in care.

HIV antiretroviral therapy (ART) can durably suppress the plasma HIV viral load which improves individual survival and dramatically reduces further HIV transmission. Achieving HIV viral suppression is a primary goal when initiating ART. Unfortunately, there are gaps throughout the continuum of HIV care in the United States where a large proportion of PLWH are not able to fully maximize the health benefits of effective ART. It is estimated that over 1.1 million Americans were living with HIV in 2009, and decreasing proportions were diagnosed (82%), linked to care (66%), retained in care (37%) and prescribed ART (33%) (1). Only 25% of all people with HIV know they are infected, get regular medical care, take ART, and achieve HIV viral suppression (1).

There is a need to implement effective interventions that focus on enhancing prevention and care to improve the health of, and to reduce HIV transmission risk among, PLWH. Several studies have shown that brief computerized interventions can reduce self-reported sexual risk behaviors and ART adherence among PLWH (2, 3, 4, 5, 6). A recent study tested the efficacy of a computerized intervention supporting ART adherence and HIV transmission risk reduction and found that intervention participants, relative to controls, experienced greater suppressed HIV-1 viral load (P=0.053), reported greater ART adherence (P=0.046), and reported fewer sexual transmission risk behaviors (P=0.040) (7). Together, these studies suggest that computerized interventions are a promising approach to improve ART adherence and safer sex behaviors among PLWH (8).

However, interventions should be developed with improved study design (e.g., large sample size) and relevant outcome measures (e.g., retention in HIV care, ART initiation, and ART adherence based on biologic measures of HIV-1 viral load suppression).

In response to this need, CDC developed Positive Health Check, a web-based video counseling intervention to improve clinical health outcomes among PLWH. Positive Health Check is a 15-20 minute English-language web-based video counseling intervention. The intervention is to be used by PLWH in HIV primary care settings to supplement existing clinical care services. The intervention aims to improve persons’ ART initiation, ART adherence (measured by suppressed HIV-1 viral load), retention in care, and sexual risk reduction (measured by incident STDs). The intervention also aims to reduce mother-to-child transmission and risk of HIV transmission through injection drug use behavior.

The Positive Health Check Evaluation Trial will be a randomized trial to test whether the Positive Health Check intervention significantly improves the abovementioned clinical outcomes. The study will be conducted by one grantee through participation with three or four HIV primary care clinics in the United States that vary by location (i.e., located in different metropolitan statistical areas with high HIV prevalence (greater than 5000 diagnosed with HIV infection by year-end 2010) as indicated in Table 23 of CDC’s 2011 HIV Surveillance Report (9) (see: http://www.cdc.gov/hiv/pdf /statistics_2011_HIV_Surveillance_Report_vol_23.pdf), type of clinic (e.g., Community Health Center, http://www.cdc.gov/hiv/pdf/statistics_2011_HIV_Surveillance_Report_vol_23.pdf

Ryan White-funded, academic-affiliated, health maintenance organization, private, or Veterans Administration clinics) and meet the identified minimum criteria for selection. The grantee and its partner clinics will conduct the trial over a 24-month period of time and must enroll a minimum of 2,320 eligible participants (1,160 per study arm). The randomized trial will also document the cost and feasibility of implementing and integrating the Positive Health Check intervention in HIV primary care clinic settings.

Participants eligible for enrollment in this trial will have one or more of the following characteristics: not currently prescribed ART (including ART naïve or persons previously prescribed ART), new patient within the last year (including new patient to the clinic or newly diagnosed), has detectable viral load (≥ 200 copies/mL), previous laboratory test for viral load more than one year ago, missed at least one HIV primary care appointment within the last year, evidence of prior STD, or documented or self-reported indication of engaging in high risk sex or injection drug use. Positive Health Check contains modules to address each of these characteristics, and persons’ navigation through the modules are guided by their personal prevention needs.

PLWH eligible and enrolled in the trial will be randomized to either the intervention arm (i.e., Positive Health Check plus standard clinical care) or to the control arm (i.e., standard clinical care only).

References:

1. United States Department of Health and Human Services, Centers for Disease Control and Prevention, “HIV in the United States: The Stages of Care.” CDC Fact Sheet. July 2012. URL: http ://www.cdc.gov/hiv/pdf/research_mmp_stagesofcare.pdf.

2. Gilbert, P., Ciccarone, D., Gansky, S. A., Bangsberg, D. R., Clanon, K., McPhee, S. J., et al.

(2008). Interactive “Video Doctor” counseling reduces drug and sexual risk behaviors among HIV-positive persons in diverse outpatient settings. PLoS ONE, 3(4), 1-10.

3. Fisher, J. D., Amico, K. R., Fisher, W. A., Cornman, D. H., Shuper, P. A., Trayling, C., et al.

(2011). Computer-Based Intervention in HIV Clinical Care Setting Improves Antiretroviral Adherence: The LifeWindows Project. AIDS and Behavior, 15(8), 1635-1646.

4. Noar, S. M., Black, H. G., Pierce, L. B. (2009). Efficacy of computer technology-based HIV prevention interventions: a meta-analysis. AIDS. 23(1), 107-15.

5. Hersch, R. K., Cook, R. F., Billings, D. W., Kaplan, S., Murray, D., Safren, S., et al. (2013).

Test of a Web-Based Program to Improve Adherence to HIV Medications. AIDS and Behavior, 17, 2963-2976.

6. Bachmann, L. H., Grimley, D. M., Gao, H., Aban, I., Chen, H., Raper, J. L., et al. (2013).

Impact of a computer-assisted, provider-delivered intervention on sexual risk behaviors in HIV-positive men who have sex with men (MSM) in a primary care setting. AIDS Education and Prevention, 25(2), 87-101.

7. Kurth, A. E., Spielberg, F., Cleland, C. M., Lambdin, B., Bangsberg, D. R., Frick, P. A., et al.

(2014). Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk:

Findings From a Randomized Controlled Trial. Journal of Acquired Immune Deficiency Syndrome, 65(5), 611-620.

8. Noar, S. M. (2011). Computer technology-based interventions in HIV prevention: State of the evidence and future directions for research. AIDS Care. 23(5), 525-33.

9. Centers for Disease Control and Prevention. HIV Surveillance Report, 2011; vol. 23. http://www http://www.cdc.gov/hiv/pdf/statistics_2011_HIV_Surveillance_Report_vol_23.pdf http://www.cdc.gov/hiv/pdf/research_mmp_stagesofcare.pdf http://www.cdc.gov/hiv/pdf/research_mmp_stagesofcare.pdf http://www.cdc.gov/hiv/topics/surveillance/resources/reports/ http://www.cdc.gov/hiv/topics/surveillance/resources/reports/

.cdc.gov/hiv/topics/surveillance/resources/reports/. Published February 2013. Accessed July 29, 2014.

Healthy People 2020 and other National Strategic Priorities

The NCHHSTP of CDC within HHS is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2020" and to measuring program performance as stipulated by the Government Performance and Review Act (GPRA). This FOA addresses the “Healthy People 2020” priority area of HIV and is in alignment with: 1) performance goal HIV-10 (developmental) to increase the proportion of HIV-infected adolescents and adults who receive HIV care and treatment consistent with current standards by 2020; 2) performance goal HIV-11 to increase the proportion of persons surviving more than 3 years after a diagnosis with AIDS by 10% (from 84% to 92.4% by 2020; and 3) performance goal HIV-12 to reduce deaths from HIV infection by 10% (from 3.7 deaths due to HIV infection per 100,000 population to 3.3 deaths due to HIV infection per 100,000 population) by 2020. For more information, please see http://www.healthypeople.gov/2020/topics-objectives/topic/hiv/objectives The National HIV/AIDS Strategy (NHAS) has also set goals and this proposed study supports goal #2 to increase access to care and improve health outcomes for people living with HIV. This proposed study also supports goal #3 to reduce HIV-related health disparities and the related anticipated results to increase the proportion of HIV-diagnosed gay and bisexual men, Blacks, and Latinos with undetectable viral load by 20%. For more information, please see http://aids.gov/federal -resources/national-hiv-aids-strategy/overview/index.html

Also related to NHAS, this study is in support of the White House’s HIV Care Continuum Initiative which calls for coordinated action to increase the number of people living with HIV in the United States who have achieved the treatment goal of controlling the HIV virus. For more information, please see http://aids.gov/federal-resources/policies/care-continuum/

Public Health Impact

Although HIV antiretroviral therapy (ART) is a life-saving intervention that both improves quality of life and reduces further HIV transmission in the community, only an estimated 25% of people living with HIV know they are infected, get regular medical care, take ART and have the HIV virus under control and suppressed. The Positive Health Check Evaluation Trial will demonstrate the feasibility and efficacy of a brief online counseling intervention to improve health outcomes of PLWH. The ultimate goal is to demonstrate that the intervention is an efficacious public health program to improve HIV care and reduce HIV transmission in the United States.

Relevant Work

Positive Health Check: CDC’s Prevention Research Branch has developed Positive Health Check a 15-20 minute English-language web-based video counseling intervention designed to improve clinical health outcomes for PLWH including ART initiation, ART adherence as measured by suppressed HIV-1 viral load, retention in care, and sexual risk reduction as measured by incident STDs. Positive Health Check also promotes protective behaviors for mother-to-child transmission and injection drug use. The intervention is to be used by English-speaking PLWH in HIV primary care to supplement existing clinical care services. A virtual doctor-actor of the patient’s choice delivers tailored messages based on a patient’s responses to screener questions and selected questions for their clinic doctor and tips to practice before their next clinic visit. Positive Health Check is housed within the CDC information technology server and internet domains and utilizes media streaming mechanisms to deliver the web-based intervention to target audiences.

The Positive Health Check (PHC) intervention is comprised of 8 modules (Opening, Treatment http://www.cdc.gov/hiv/topics/surveillance/resources/reports/ http://www.cdc.gov/hiv/topics/surveillance/resources/reports/ http://www.healthypeople.gov/2020/topics-objectives/topic/hiv/objectives http://aids.gov/federal-resources/national-hiv-aids-strategy/overview/index.html http://aids.gov/federal-resources/national-hiv-aids-strategy/overview/index.html http://aids.gov/federal-resources/policies/care-continuum/

Readiness, Adherence, Retention in Care, Sex Risk Reduction, Mother-to-Child Transmission, IDU and Closing) which are tailored to patients based on their responses to screener questions and personal selections. Development work has included the filming of all video clips with virtual medical staff, as well as programming the intervention to allow for an interactive, tailored delivery of the intervention. PHC (programming and video clips) is housed within the CDC domain and utilizes a streaming media mechanism to deliver the web-based intervention. Sample intervention video clips can be viewed here: http://www.cdc.gov/hiv/policies/funding/positiveHealthVideos.html.

CDC’s 2011 HIV Surveillance Report: Centers for Disease Control and Prevention. HIV Surveillance Report, 2011; vol. 23. Published February 2013. Accessed July, 29, 2014.

http://www.cdc.gov/hiv/topics/surveillance/resources/reports/.

Prevention IS Care: The Prevention Is Carecampaign encourages health care providers to counsel PLWH to reduce HIV-related risk behaviors and maintain low-risk behaviors. Prevention IS Care provides health care providers with tools that can be used on a daily basis with persons who are living with HIV. Informational posters and patient education brochures improve persons' knowledge about HIV, facilitate information exchange and strengthen persons' ability to make healthy choices.

Tools and continuing education opportunities are available through http://www.cdc.gov/actagainstaids /campaigns/pic/index.html.

CDC’s Winnable Battles: This FOA addresses one of CDC’s Winnable Battle goals by:

Intensifying HIV prevention efforts in communities where HIV is most heavily concentrated.

Expanding targeted efforts to prevent HIV infection using a combination of effective, evidence-based approaches for persons living with HIV and those at high risk of infection.

Maximizing the proportion of people with HIV who have suppressed viral load by improving diagnosis, linkage and retention in care, and antiretroviral provision and adherence.

Improving data monitoring, dissemination, and feedback.

Educating persons living in the US about the threat of HIV and how to prevent it.

Additional information about these key actions is available at: http://www.cdc.gov/winnablebattles /targets/pdf/hiv-winnablebattles-progressreport.pdf

CDC HIV Intervention and Dissemination Programs (examples): CDC’s Capacity Building Branch (CBB) in the Division of HIV/AIDS Prevention (DHAP) develops a national dissemination and technical assistance plan and makes interventions available to any agency wishing to implement them in their communities. CBB is currently translating five HIV medication adherence strategies to improve health outcomes and reduce risk of HIV infections. In addition, CBB is preparing a training curriculum for patient navigators to actively engage people living with HIV in enhancing entry into HIV care, promote medication adherence, and facilitate retention in HIV care. Finally, CBB is disseminating the Anti-Retroviral Treatment and Access to Services (ARTAS) intervention, which is an individual-level, multi-session intervention with the goal of linking recently diagnosed persons with HIV to medical care soon after receiving their positive test result. Additional information about these activities is available at: http://www.effectiveinterventions.org/en/HighImpact Prevention/BiomedicalInterventions/MedicationAdherence.aspx.

CDC’s Epidemiology Branch in DHAP is implementing and evaluating a multi-component HIV clinic-based intervention called APTCare to lower HIV-1 viral load among persons, and improve persons’ adherence to ART, retention in care, and safer-sex practices. Persons who have a detectable viral load are encouraged to do a brief computer-based intervention (CBI) available at the clinic and work with a counselor or prevention case manager to provide additional support. The CBI, just one http://www.cdc.gov/hiv/topics/surveillance/resources/reports/ http://www.cdc.gov/actagainstaids/campaigns/pic/index.html http://www.cdc.gov/actagainstaids/campaigns/pic/index.html http://www.cdc.gov/winnablebattles/targets/pdf/hiv-winnablebattles-progressreport.pdf http://www.cdc.gov/winnablebattles/targets/pdf/hiv-winnablebattles-progressreport.pdf http://www.effectiveinterventions.org/en/HighImpactPrevention/BiomedicalInterventions/MedicationAdherence.aspx http://www.effectiveinterventions.org/en/HighImpactPrevention/BiomedicalInterventions/MedicationAdherence.aspx aspect of the program, engages the persons with questions and provides motivational messages, ideas, and tips for improving ART adherence, clinic attendance and sexual risk reduction as needed.

For more information, see http://clinicaltrials.gov/show/NCT02044484.

2. Approach

CDC is proposing to conduct a randomized trial to determine if Positive Health Check, a brief online video counseling intervention improves clinical health outcomes among English-speaking PLWH in HIV primary care. Positive Health Check is a 15-20 minute English-language web-based video counseling intervention, developed and maintained by CDC, which is intended to be used by PLWH in HIV primary care to supplement existing clinical care services.

The intervention aims to increase viral load suppression and reduce risk of HIV transmission by targeting ART initiation, ART adherence as measured by suppressed HIV-1 viral load, retention in care, and sexual risk reduction as measured by incident STDs. The intervention also briefly addresses mother-to-child transmission and injection drug use behavior.

Figure 1. Positive Health Check Flow Diagram

The following describes a typical patient’s use of the Positive Health Check intervention. A schematic of the intervention flow is shown in Figure 1 above (MTCT= Mother-to-Child HIV Transmission; IDU = Intravenous Drug Use).

Clinic persons log on to Positive Health Check using a laptop, desktop computer or tablet with WiFi or Internet access. After a virtual “nurse” welcomes the patient to the intervention, the patient completes a brief demographic survey. Next, the patient chooses a virtual “doctor” to work with http://clinicaltrials.gov/show/NCT02044484 during the session. The virtual doctor delivers education and prevention messages tailored to the patient’s risk behaviors, as determined by the patient’s responses to screener questions on six topics:

ART initiation, ART adherence, retention in care, sexual risk reduction, mother-to-child transmission, and injection drug use behavior. The patient then selects “tips,” which are prevention strategies to practice before their next clinic visit. Examples of prevention “tips” for improving ART adherence include: (1) “When taking a trip, always keep your HIV meds with you, not in your suitcase; and bring extra doses in case of delays;” (2) “Set a reminder system like a note or set a daily alarm on your cell phone. You can also use an app or online reminder service;” and (3) “Keep an extra dose at work or with you in case of emergencies.” Examples of prevention “tips” for improving retention in care include: (1) “If you have to miss an appointment, call the clinic ahead of time and reschedule it;” and (2) “Line up transportation to the clinic or arrange child care.”

At the end of the session, the patient is invited to view “Extra Info” which includes videos and information materials on selected topics of interest. Finally, the patient is provided with a handout of the questions they selected to ask their provider during their clinic visit and tips they committed to practice before their next visit. The patient may choose to have the handout emailed to their private email address or shared with the provider. If unable to finish the intervention during the clinic visit, the patient may request to have a secure link to the intervention emailed to his/her private email address.

During the period of implementation of 24 months, persons will be expected to log on and complete the Positive Health Check intervention during each regularly scheduled clinic visit. It is anticipated that each patient enrolled in the trial will complete the intervention up to three times. Persons will also have the option of completing Positive Health Check on their personal devices while at home or at another location if they are unable to complete the intervention while in the clinic. The Positive Health Check intervention will be hosted on a secure server and maintained by CDC for the duration of the study.

After the award has been granted, CDC will work with the grantee to provide access to Positive Health Check materials and to train the grantee on intervention implementation. Following this orientation, CDC will collaborate with the grantee to develop a trial protocol. Although the trial details will be determined at that time, core activities and outcomes are discussed in this FOA.

To conduct the randomized trial, the applicant/prospective grantee will select and collaborate with three or four HIV primary care clinics in the United States to enable the recruitment of a minimum of 2,320 persons required for this study, with a minimum of 580 to a maximum of 1,160 enrolled from each clinic.

Participating HIV clinics will:

Vary by location and type:

Each clinic will be located in different metropolitan statistical areas with high HIV prevalence (greater than 5000 diagnosed with HIV infection by year-end 2010) as indicated in Table 23 of CDC’s 2011 HIV Surveillance Report (see: http://www.cdc.gov/hiv/pdf/statistics_2011_HIV_ Surveillance_Report_vol_23.pdf).

Clinics will be of different clinical service types (e.g., Community Health Centers, Ryan White-funded, academic-affiliated, health maintenance organization, private, or Veterans Administration clinics) and serve a patient population whose sociodemographics (e.g., race/ethnicity, gender, and socioeconomic status) are representative of people living with HIV in the applicant’s local jurisdiction.

The three or four clinics must be a combination of and represent at least two different clinical service types (e.g., two Community Health Centers and one Ryan White or two Ryan White and one veterans Administration).

Meet the minimum criteria for eligibility as follows:

HIV Clinic Eligibility Criteria HIV clinics working with the applicant will meet all of the following criteria in order to be determined eligible for participation in the randomized trial study.

Serve a patient population whose sociodemographics (e.g., race/ethnicity, gender, and socioeconomic status) are representative of people living with HIV in the local jurisdiction;

Be located in a United States Metropolitan Statistical Area of high HIV prevalence (greater than 5000 diagnosed with HIV infection by year-end 2010) as indicated in Table 23 of CDC’s 2011 HIV Surveillance Report http://www.cdc.gov/hiv/pdf/statistics_2011_HIV_Surveillance_Re port_vol_23.pdf Be representative of the types of HIV primary care clinics in the clinic’s jurisdiction (e.g., Community Health Centers, Ryan White-funded, academic-affiliated, private, Veterans Administration);

Use electronic medical records (EMRs) or other clinic databases to access patient clinical data, including laboratory-confirmed viral load (copies/mL), CD4 cell counts, STD screening and treatment history, ART prescriptions and refills, tests for pregnancy and provision of prescription for emergency contraception, and clinic attendance for HIV primary care;

Perform routine STD screening as part of routine HIV care;

Have access to sufficient numbers of clinic patients to warrant inclusion in the research study where approximately 580 to 1,160 persons are enrolled by each participating clinic. When combined, the 3 to 4 clinics must enroll a minimum of 2,320 persons.

Provide a letter of support to conduct the Positive Health Check Evaluation Trial over a 24-month period of time;

Identify and budget for a “champion” within the clinic (e.g., Medical Director) to endorse and promote trial activities over the 24-month period of participation in the trial (list as a key person in the application and include salary and percent effort in the detailed budget);

Identify, and/or recruit, and budget for a full-time (12 calendar months) study coordinator and part-time (minimum 20% effort) data manager for the 24-month period of participation in the trial (list as key persons in the application and include salaries and percent effort in the detailed budget);

Agree to share clinic data with the grantee and with CDC; and Perform only the Positive Health Check trial and no other coincident intervention or study using resources from this FOA.

The successful applicant will collect, from each eligible clinic, the clinic-specific information and clinical service data described below. The applicant will use these data in determining selection for participation. Included in the Appendix section of the application should be the names of the three or four collaborating clinics that were selected for participation, the associated clinic-specific information and clinical service data, a list of the qualifying clinics from which the participating clinics were selected, a description of how the participating clinics were selected, and a description of how these clinics meet the minimum criteria to participate in the randomized trial (e.g., provide HIV care to a minimum number of persons).

Required Clinic-Specific Information and Clinical Service Data

Number of HIV-positive persons served by the clinic over 12 months, including race/ethnicity,1.

sex at birth, gender, sexual orientation, and HIV transmission category.

Estimated number of HIV-positive persons on ART, number of persons who are not virally suppressed, number of persons with inconsistent or irregular clinic attendance, and number of new persons referred to the clinical annually.

2.

Location of the clinic including state, city, and neighborhood(s).3.

Length of time clinic has provided HIV and STD treatment and care services.4.

Use of electronic medical records (EMRs) and other clinic databases to access patient clinical data including laboratory-confirmed viral load (copies/mL), CD4 cell counts, STD screening and treatment history, ART prescriptions and refills, pregnancy test results, request and provision of prescription for emergency contraception, and clinic attendance for HIV primary care.

5.

Conducts STD screening as part of routine HIV care. 6.

Nature of all HIV/STD prevention or other health promotion services provided at the clinic.7.

Can identify a “champion” within the clinic (e.g., Medical Director) to endorse and promote the randomized trial.

8.

Agree to share data with grantee and CDC.9.

Can identify a full time (12 months) project coordinator and part-time data-manager to oversee and manage the randomized trial (list as key persons in the application and include salaries and percent effort in the detailed budget);

10.

Statement of whether the proposed clinics have participated in any previous pilot test of the Positive Health Check intervention.

11.

Confirmation that the applicant proposes to evaluate the intervention Positive Health Check and no other intervention or study using resources funded from this FOA.

12.

The applicants awarded through this FOA will ensure that appropriate security and confidentiality and data sharing agreements are in place between the grantee’s organization and the three or four collaborating HIV primary care clinics before work is initiated. Whereas multiple clinics will participate in this trial, the collaboration between each clinic and the grantee will be bilateral.

Therefore, each clinic will share information with the grantee as part of this trial, but that information will not be shared with other clinics in the trial.

Implementation of the study will determine the efficacy of the Positive Health Check intervention for improving clinical health outcomes of English-speaking PLWH in primary care in the United States (Research Objective #1). Collaborating clinics will identify eligible persons for the trial including, but not limited to, persons with one or more of the following characteristics: not currently prescribed ART (including ART naïve or persons previously prescribed ART), new patient within the last year (including new patient to the clinic or newly diagnosed), has detectable viral load (≥ 200 copies/mL), previous laboratory test for viral load more than one year ago, missed at least one HIV primary care appointment within the last year, evidence of prior STD, or documented or self-reported indication of engaging in high risk sex or injection drug use.

Within each clinic, eligible persons will be identified by a full-time onsite study coordinator through examination of EMRs, medical charts, laboratory reporting data, and patient appointment records.

Eligible persons will be randomized into the intervention arm (i.e., Positive Health Check plus standard clinical care) or the control arm (i.e., standard clinical care only). A computer program will be developed by the grantee to randomize persons. The computer program will also be used by the study coordinator to track patient exposure to the intervention during at least 3 regularly scheduled clinic visits. The grantee will provide sufficient computers, laptops or tablets to each participating clinic to make the Positive Health Check intervention available to eligible persons in the intervention arm.

arm.

A quantitative assessment will include a comparison of outcomes among persons receiving the Positive Health Check intervention plus standard clinical care (intervention arm) with those persons receiving standard clinical care only (control arm). The study will seek to detect changes in:

the number and proportion of persons with suppressed HIV-1 viral load;

the number and proportion of persons prescribed ART;

the number and proportion of persons attending scheduled HIV care appointments;

the number and proportion of new cases of sexually transmitted diseases (STDs); and the number and proportion of persons with a documented unplanned pregnancy or request for emergency contraception.

The primary study question for this trial will be whether persons in the intervention arm are more likely to achieve viral suppression within 12 months after enrollment compared to persons in the control arm. The proportions of persons in the control and intervention arms who achieve HIV-1 viral load suppression will be compared using Fisher’s Exact Test with a two-sided significance level of 5%. Assuming that the proportion of successes in the control and intervention arms are 70% and 77%, respectively, a relative difference of 10%, and allowing for an annual attrition rate of 25%, a minimum sample size of 2,320 persons (or 1,160 persons per study arm) will be required to have 80% power to reject the null hypothesis that the true proportion of successes is the same in both arms.

Major data elements to be collected by the grantee during the randomized trial will include routine clinical data including HIV-1 viral load laboratory results, ART prescription and refill receipt information, persons’ attendance of scheduled clinic appointments, STD screening and treatment results, test for unplanned pregnancy, and provision of prescription for emergency contraception.

Additional data elements will include, but are not limited to, information on basic patient demographics (e.g., month and year first tested HIV positive, age, biological sex, race, ethnicity, HIV risk exposure category, and primary insurance), clinic type, and trial classification (i.e., intervention vs. control).

In addition, the grantee will conduct in the three or four study clinics focus groups and in-depth structured interviews with key staff including, but not limited to, clinic directors/managers, case managers, nurses and physicians (Research Objective #2). The focus groups and interviews will be administered intermittently throughout the 24-month period of study implementation. These data will address how Positive Health Check fits into clinic flow and routine clinical practice; the feasibility of implementing the intervention in diverse clinic environments, including those with limited resources; how many persons are offered the intervention; number of exposures to the intervention;

and how the intervention impacts patient-provider communication. CDC will provide the grantee with process data collected by the Positive Health Check intervention which will be programmed to automatically upload these process data to a database maintained by the CDC. The database will include several parameters including patient input in response to module-specific risk screener questions, length of time patient is logged on to the intervention, use of the email option, use of the handout option, number of persons that completed the intervention, and total number of individual patient exposures to the intervention. The intervention is considered complete when the patient has visited each intervention module. The grantee will use this information in statistical analyses.

The grantee will collect and document information on the cost of Positive Health Check intervention implementation (Research Objective #3). Cost factors to include but not limited to staff time, computer equipment, and office supplies (fax/printer ink, etc.) will be identified. Additional considerations will be reviewed and identified after award.

Finally, the grantee will collect descriptive data on the standard of care for each HIV primary care clinic participating in the randomized trial including for example the use of risk reduction messages and appointment reminders (Objective #4.).

Consistent with the Consolidated Standards of Reporting Trials (CONSORT) statement (see: http://www .consort-statement.org/), the application must include a plan for an intention-to-treat analysis (i.e., an analysis of persons in study arms as originally assigned, analysis of persons regardless of the level of intervention exposure, and analysis using appropriate imputations to account for missing data due to attrition or other reasons), and individual-level randomization to study arms.

Objectives/Outcomes

Grantees awarded under this FOA will implement the Positive Health Check Trial in three or four HIV primary care clinics and must address each of the following research objectives:

Objective #1: Implement a randomized trial to test the efficacy of the Positive Health Check intervention for improving clinical health outcomes including:

ART initiation;a.

ART adherence (measured by suppressed HIV-1 viral load);b.

Retention in care;c.

Sexual risk reduction (measured by incident STDs);d.

Other measures suggesting potential HIV transmission risk (e.g., unplanned pregnancy, request for emergency contraception).

e.

Outcomes:

1. HIV-1 Viral Load Suppression: Calculate the number and proportion of HIV-infected persons who achieve viral load suppression (less than 200 copies/mL) within 12 months after randomization to either the intervention plus standard care study arm or the standard care only study arm.

a. All persons randomized to the intervention arm or control arm will be included in the denominator.

b. Outcomes will be dichotomized as either:

i. Achieved viral load suppression: suppressed viral load result (less than 200 copies/mL) within 12 months of the date of randomization.

ii. Did not achieve viral load suppression: either viral load results within 12 months of the date of randomization were not suppressed (greater than or equal to 200 copies/mL) or the patient had no viral load results.

c. HIV primary care clinic laboratory reporting data will be used to measure these outcomes.

2. Durable HIV-1 Viral Load Suppression: Calculate the number and proportion of HIV-infected individuals who achieved durable viral load suppression [two suppressed viral load results (less than 200 copies/mL) at least three months apart within 18 months] from the date of randomization to either less than the intervention plus standard care study arm or the standard care only study arm.

a. All persons randomized to the intervention arm or control arm will be included in the denominator.

http://www.consort-statement.org/ http://www.consort-statement.org/

b. Outcomes will be dichotomized as either:

i. Achieved durable viral load suppression: two suppressed viral load results (less than 200 copies/mL) at least three months apart within 18 months of the date of randomization.

ii. Did not achieve durable viral load suppression: did not have two suppressed viral load results (less than 200 copies/mL) at least three months apart within 18 months of the date of randomization.

c. HIV primary care clinic laboratory reporting data will be used to measure these outcomes.

3. ART initiation: Calculate the number and proportion of HIV-infected persons naïve to ART (or treatment experienced but not currently prescribed ART) who receive a prescription for ART within 90 days from the date of randomization to either the intervention plus standard care study arm or the standard care only study arm.

a. All persons randomized to either the intervention arm or control arm who were not currently prescribed ART therapy at randomization will be included in the denominator.

b. Outcomes will be dichotomized as either:

i. Prescribed ART within 90 days of the date of randomization.

ii. Was not prescribed ART within 90 days of the date of randomization.

c. HIV primary care clinic records will be used to measure these outcomes.

4. Retention in care: Calculate the number and proportion of HIV-infected persons who attend one clinic visit within 90 days from the date of randomization to either the intervention plus standard care study arm or standard care only study arm.

a. All persons randomized to the intervention arm or control arm will be included in the denominator.

b. Outcomes will be dichotomized as either:

i. Retained in care: Attended one clinic visit within 90 days of the date of randomization.

ii. Not retained in care: Did not attend one clinic visit within 90 days of the date of randomization.

c. HIV primary care clinic patient appointment records will be used to measure these outcomes.

5. Engaged in care: Calculate the number and proportion of HIV-infected individuals who are engaged in care as measured by two clinic visits at least three months apart within 12 months from the date of randomization to either the intervention plus standard care study arm or the standard care only study arm.

a. All persons randomized to either the intervention arm or control arms will be included in the denominator.

b. Outcomes will be dichotomized as either:

i. Engaged in care: Attended two clinic visits at least three months apart within 12 months of the date of randomization.

ii. Not engaged in care: Did not attend two clinic visits at least three months apart within 12 months of the date of randomization.

c. HIV primary care clinic patient appointment records will be used to measure these outcomes.

6. Incident STD: Calculate the number and proportion of HIV-infected individuals who are diagnosed with an incident STD from the date of randomization to either…