A Nurse-led Intervention to Extend the HIV Treatment Cascade for Cardiovascular Disease Prevention
Phase: NA
Conditions: HIV/AIDS, Hypertension, Hyperlipidemias
Sponsor: Case Western Reserve University

 
 
 
 
 
 
 
A nurse-led intervention to extend the HIV treatment 
cascade for cardiovascular disease prevention 
(EXTRA-CVD) 
 
Protocol 
Version Date: September 7, 2022 
 
ClinicalTrials.gov Identifier: 
NCT03643705 
 

 
Protocol 
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September 7, 2022 
 
Protocol Modifications (more recent changes listed first) 
Date  
Summary of Changes 
9/7/2022 
x 
Modified Aim 3 qualitative data collection to specify that the 
prevention nurses at each site will be recruited to participate in 
healthcare worker interviews (pp. 46-47). 
x 
Revised Aim 3 qualitative interview guide.  Added additional questions 
for prevention nurses regarding motivational interviewing.   
x 
Added a protocol to re-engage the design team to inform the 
development of a composite measure of dose (pp. 31-32 and 
Appendix T).   
x 
Added a new consent form for the new activities related to design 
team re-engagement. 
10/13/2021 
x 
Given Dr. Longenecker's physical transition to the University of 
Washington (UW), Dr. Barbara Gripshover, MD will assume the role as 
University Hospitals' site PI (p. 7) 
x 
Dr. Longenecker’s contact information will be replaced by Dr. 
Gripshover’s for UH patient communications and nurse-patient 
communications of clinically significant information (p. 54), 
recruitment letters and follow-up letters (local site documents), and 
informed consent forms (p. 57) 
x 
Recruitment goals for AAIM-High (Arm 4) will be updated from 25 per 
site (75 total) to 35 per site (110 total) (pp. 20-21) 
7/9/2021 
x 
Added AAIM-High Observation Recording Script to obtain verbal 
consent for recording visits to later be observed by study staff (p. 43) 
x 
Modified approach to Aim 3 qualitative data collection from PLHIV (n-
36) and healthcare team members (n=36) to allow for telephone 
interviews instead of in-person interviews. 
x 
Appendix S: Key Informant Interview Guides for PLHIV and Clinicians 
(p. 117) 
4/12/2021 
x 
Added Phone Script for Duke Health to obtain verbal consent for 
access to patient EMR to schedule baseline visit in EMR to allow for 
better clinic workflow (pp. 22-23) 
x 
Added Follow-Up Letter to re patients who are lost to follow up via 
telephone methods (pp. 31) 
x 
Added Appendix Q: AAIM High-specific Process Evaluation Checklist to 
ensure fidelity of intervention and standardization of study procedures 
(p. 110) 
x 
Added Appendix R: AAIM High clinic context form (p. 114) 
2/12/2021 
x 
Added plan to enroll subset of aim 2 participants into aim 4 (p. 20) 
x 
Added inclusion criteria to aim 4 inclusion/exclusion table (p. 20) 
x 
Added virtual consent procedure for aim 4 implementation 
effectiveness trial, which applies only to participants who were 
enrolled in aim 2 (p. 23) 

 
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x 
Added descriptions of finalized aim 4 adaptations decided upon by the 
design team (p. 46) with forms added as appendices O and P (pp. 106, 
107) 
x 
Added “Sharing of Results with Research Participants” (pp. 54-55) 
10/29/2020 
x 
Added a 5th study objective (pp. 4, 12) 
x 
Added aim 4 qualitative research methods by study population to 
table 3 (p. 13) 
x 
Added aim 4 to study design (p. 13) 
x 
Added enrollment information for aim 4 (p. 18) 
x 
Added consent procedures for aim 4 (p. 22) 
x 
Added study visit procedures for aim 4 (p. 45) 
x 
Added timeline for aim 4 (p. 47) 
6/18/2020 
x 
Added protocol for motivational interviewing component of nurse 
clinical skill building into Aim 3 
x 
Added language concerning audio recordings for motivational 
interviewing purposes and patient confidentiality  
x 
Added Appendix M: Behavior Change Counseling Index (BECCI) for 
Measuring Practitioner Motivational Interviewing Skills 
x 
Clarification that the window for study procedures during the COVID 
pandemic (visits, surveys, outcome BP/cholesterol) is +/- 21 days from 
the “target visit date”.  The target visit date is calculated as 4-, 8-, or 
12-months from the baseline visit (p. 37) 
4/17/2020 
x 
Added COVID-19 instruments to remote visit procedures 
x 
Added table of COVID-19 survey instruments 
x 
Added COVID-19 symptom screening and referral to needed services 
x 
Added semi-structured interviews for impacts of COVID-19 on self-
management of cardiovascular health among PLWH 
x 
Added COVID-19 key informant interview guide in Appendix C 
x 
Submitted COVID-19 key informant interview telephone script with 
confirmation of verbal informed consent to participate 
03/24/2020 
x 
Added protocol for virtual visits during the novel coronavirus outbreak 
through secure phone calls and/or site-specific HIPAA-compliant 
online platforms (p. 36) 
x 
Submitted three site-specific letters to participants to inform them of 
changes in study visit format and methods to contact study team 
during novel coronavirus outbreak 
10/29/2019 
x 
Added 2 week window for date of in person visits 
x 
Added table of BP and cholesterol diagnosis terms for determining 
cascade category 
x 
Added clarification of how many attempts will be made to reach 
potentially eligible patients by phone 
x 
Added additional language on recruitment strategies 

 
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x 
Added checklist for observation of study visit to ensure fidelity 
9/16/2019 
x 
Minor changes to statistical analysis in response to NIH review 
9/9/2019 
 
 
 
 
 
x 
Updated BP and Cholesterol treatment protocols 
x 
Incorporated process oriented design team recommendations about 
intervention adaptation. 
x 
Added additional detail regarding the aim 3 process evaluation, 
including the assessment of provider trust and communication ties 
x 
Added verbal consent script to obtain age, sex, gender identity, and 
race/ethnicity from persons who are screened but who decline to 
participate in the study 
x 
Added a recruitment letter and MyChart message (Duke only).  Added 
a telephone script for the follow-up screening call. 
2/7/2019 
x 
Added additional detail to design team process (sub-aim 1.1) 
x 
Added 3 additional consents forms for the design team process 
o Design team members (focus group and survey) 
o PLHIV pilot participants (focus groups/pilot intervention) 
o Feasibility testing among health workers (interview) 
10/29/2018 
 
 
 
 
x 
Added clinic variables checklist (p. 18 and Appendix D) 
x 
Minor change to wording of inclusion criteria #5 and exclusion criteria 
#1 related to a simplification of the definition of hyperlipidemia 
x 
Minor change to cholesterol treatment algorithm (p. 22) clarifying how 
the prevention nurse will determine non-HDL goal for the purposes of 
treatment recommendations. 
x 
Added scripts for Aim 1 phone consent for (a) healthcare providers 
and (b) PLHIV (Duke site) 
x 
Added recruitment letter for Aim 1 (Duke site) 
x 
Added clinicaltrials.gov registration number 
8/6/2018 
x 
Added adherence surveys for PLHIV focus group and clinical trial 
participants 
 
 
 

 
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Title 
A nurse-led intervention to extend the HIV treatment cascade for cardiovascular 
disease prevention (EXTRA-CVD) 
Principal 
Investigators 
Christopher Longenecker, MD 
Allison Webel, RN, PhD   
Hayden Bosworth, PhD 
Grant 
Support 
National Heart, Lung, and Blood Institute 
Phase 
4 
Population 
Adults living with HIV on antiretroviral therapy with co-morbid hypertension and 
hyperlipidemia 
Sites 
1. University Hospitals Cleveland Medical Center, Special Immunology Clinic, 
11100 Euclid Avenue, Cleveland, Ohio, 44106 
2. MetroHealth Medical Center, Infectious Disease Clinic, 2500 Metrohealth Dr., 
Cleveland, OH, 44109 
3. Duke Health, Infectious Disease Clinic, 40 Duke Medicine Circle, Durham, NC 
27710 
4. University of Washington, 1959 NE Pacific St., Seattle, WA 98195 
Duration 
12 months 
Agent or 
Intervention 
Multi-component health care delivery intervention  
1. Nurse-led care coordination 
2. Nurse-managed medication protocols and adherence support 
3. Home blood pressure monitoring 
4. Electronic medical records (EMR) support tools 
Objectives 
1. Conduct a baseline assessment of ASCVD preventive care and perceptions of 
ASCVD risk in the HIV specialty clinic environment. 
2. Adapt the EXTRA-CVD intervention components to the HIV specialty clinic 
context with key stakeholder input and data from the baseline assessments 
3. Evaluate the 12-month efficacy of the EXTRA-CVD intervention to improve BP 
and cholesterol control in PLHIV 
4. Conduct a process evaluation of the EXTRA-CVD intervention 
5. Evaluate the 12-month efficacy of an adapted virtual intervention to improve blood 
pressure in PLHIV 
Inclusion 
criteria 
1. Age 1 years 
2. Confirmed HIV+ diagnosis  
3. Undetectable HIV viral load: defined as the most recent HIV viral load <200 
copies/mL, checked within the past year (assessed via chart abstraction)  
4. Hypertension: defined as systolic BP >130 mmHg on  2 occasions in the past 12 
months or on an antihypertensive medication (assessed via chart abstraction), and 
5. Hyperlipidemia: defined as a non-HDL cholesterol >130 mg/dL or on cholesterol 
lowering medication 

 
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Exclusion 
criteria 
1. On lipid-lowering medication solely for secondary prevention of ASCVD events 
with evidence of pre-medication non-HDL which was already below 100mg/dL 
2. On anti-hypertensive medications solely for a non-hypertension indication (e.g. 
systolic heart failure), 
3. Severely hearing or speech impaired, or other disability that would limit 
participation in the intervention components, and 
4. In a nursing home and/or receiving in-patient psychiatric care.  
5. Terminal illness with life expectancy < 4 months 
6. No reliable access to a telephone  
7. Pregnant, breast-feeding, or planning a pregnancy during the study period 
8. Planning to move out of the area in the next 12 months 
9. Non-English speaking 
Endpoints 
Primary Endpoints  
x 12-month change in systolic blood pressure 
Secondary Endpoints 
x 12-month change in non-HDL cholesterol 
x Change in the extended cascade categories [(1) % appropriately diagnosed, (2) % 
appropriately managed, and (3) % at treatment goal] 
 
 
 

 
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Key Roles 
 
Co-Principal Investigator 
Chris Longenecker, MD 
University of Washington 
ctlongen@uw.edu  
 
Site Principal Investigator 
Barbara Gripshover, MD 
 
 
 
 
Professor of Medicine 
Case Western Reserve University 
 
 
 
 
University Hospitals Cleveland Medical Center 
 
 
 
 
10100 Euclid Avenue, Cleveland Ohio 44106 
 
 
 
 
(216)844-5876 
Barbara.Gripshover@uhhospitals.org  
 
 
Co-Principal Investigator 
Allison R. Webel, RN, PhD 
University of Washington 
 
 
 
 
awebel@uw.edu 
 
Co-Principal Investigator 
Hayden Bosworth, PhD 
Professor of Medicine 
Duke Department of Population Health Sciences 
411 West Chapel Hill St, Suite 600, Durham, NC 27701 
919-286-6936 
boswo001@duke.edu  
  
Co-Investigators 
 
Corrilynn Hileman, MD 
MetroHealth Medical Center 
Cleveland, OH 
 
Rajesh Vedanthan, MD 
New York University 
New York, NY 
 
Gerald Bloomfield, MD 
Duke University School of Medicine 
Durham, NC 
 
Lance Okeke, MD 
Duke University School of Medicine 
Durham, NC 
 
Lead Statistician 
Valerie Smith 
Duke University School of Medicine 
Durham, NC 

 
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1. Background 
The HIV/AIDS treatment cascade model was developed to assess how people living with 
HIV infection (PLHIV) access care and treatment. The model includes sequential steps in care 
including—(1) diagnosis, (2) prescription of appropriate antiretroviral therapy (ART), and (3) 
suppression of detectable HIV virus in the blood. These metrics are familiar to HIV-providers 
and integral to continuous quality improvement initiatives at HIV specialty clinics across the 
United States, where most PLHIV receive care1.  
PLHIV are known to have a 1.5-2x higher risk of atherosclerotic cardiovascular disease 
(ASCVD) compared to uninfected individuals, a risk that persists despite viral suppression on 
ART2,3. Thus, once PLHIV achieve the final step of the HIV treatment cascade, providers have 
an important opportunity to focus on preventing ASCVD and other non-AIDS comorbidities. We 
envision extending the treatment cascade for high blood pressure (BP) and high cholesterol, 
which account for much of the population-level ASCVD risk in PLHIV4, as follows: Step 1, 
appropriate screening and diagnosis; Step 2, appropriate treatment; and Step 3, achievement of 
guideline-based treatment targets. Currently, PLHIV are sub-optimally treated for high BP and 
cholesterol5-7, possibly due to low perceived risk for ASCVD8 or challenges in primary care 
coordination between HIV specialists and non-HIV providers9. Non-physician led approaches 
may address these barriers. Our team has experience testing non-physician led ACSVD 
prevention interventions in the general population10-15, including a nurse-led intervention 
supported by home BP monitoring that lowered systolic BP by 6 mmHg compared to usual 
care12.    
Our overarching goal is to improve the BP and cholesterol treatment cascade for PLHIV 
on suppressive ART to reduce ASCVD risk. Guided by a RE-AIM framework (Reach x 
Efficacy—Adoption, Implementation, Maintenance), and using a mixed-methods clinical 
effectiveness trial design, our experienced multi-disciplinary team will test a contextually 
adapted ASCVD prevention nurse-led intervention (EXTRA-CVD) to reach guideline-based BP 
and cholesterol targets. The study will be conducted in three racially and ethnically diverse clinic 
contexts [University Hospitals (Cleveland, OH), MetroHealth (Cleveland, OH) and Duke Health 
(Durham, NC)] that are broadly representative of HIV specialty care in the US.   
 
2. Significance  
What is the HIV/AIDS treatment cascade? The HIV/AIDS treatment cascade model 
was developed to assess how people living with HIV infection (PLHIV) access care and 
treatment. The model examines sequential steps including—(1) diagnosis, (2) prescription of 
appropriate antiretroviral therapy (ART), and (3) suppression of the HIV virus in the blood. This 
model led to the ambitious Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 
initiative,16 with large scale implementation research projects worldwide aiming to achieve these 
outcomes: 90% of PLHIV who know their status, 90% of those on ART, and 90% of those on 
ART being virally-suppressed. The cascade metrics are familiar to HIV-providers as mandated 
core performance measures of the Health Resources and Services Administration (HRSA) of the 
US Department of Health & Human Services,17 and are a focus of quality improvement 
initiatives in HIV specialty clinics across the US. Additionally, supporting research to improve 

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the HIV cascade is a priority of the NIH as reflected, for example, in the recently released PA-
17-194 "Targeted Implementation Science to Achieve 90/90/90 Goals for HIV/AIDS Prevention 
and Treatment (R01)"18. 
Why extend the treatment cascade for ASCVD prevention?  For those who have 
achieved durable viral suppression (75-80% of patients in our settings), the focus of care should 
include prevention of non-AIDS comorbidity including ASCVD. PLHIV are known to have a 
1.5-2x higher risk of ASCVD compared to uninfected individuals independent of known 
confounders such as high cholesterol and smoking2,3. Although HIV-specific factors play a role, 
traditional risk factors account for the vast majority of risk on a population level.  In an analysis 
of nearly 30,000 PLHIV from the North American AIDS Cohort Collaboration on Research and 
Design (NA-ACCORD) study, the top two risk factors with the greatest population level impact 
on myocardial infarction risk were (1) high cholesterol and (2) high blood pressure, with 
population attributable risks far exceeding low CD4+ T-cell count or elevated viral load4. 
Unfortunately, uptake of guideline-based therapies for high BP and cholesterol is sub-optimal 
among PLHIV5-7.   
We envision extending the 
HIV treatment cascade for two key 
CVD risk factors—blood pressure 
and cholesterol—to improve uptake 
of guideline-based ASCVD 
prevention therapies. Step 1, 
PLHIV should have their blood 
pressure and cholesterol screened, 
and abnormal values should be 
appropriately diagnosed as 
hypertension and hypercholesterolemia in the medical record; Step 2, those with hypertension or 
hypercholesterolemia should be prescribed appropriate guideline-based therapies; and Step 3, all 
should achieve guideline-based treatment goals. Developing the HIV treatment cascade for 
prevention of non-AIDS comorbidities is a logical downstream extension of the treatment 
cascade paradigm, just as the HIV prevention cascade is extending the treatment cascade further 
upstream19 (Figure 1).   
Blood pressure and 
cholesterol targets matter. To our 
knowledge, no HIV-specific blood 
pressure guidelines exist; however, 
international guidelines generally 
agree that treating to a target systolic 
blood pressure of 140mmHg for most 
patients is appropriate, while 
acknowledging that certain groups 
may merit more aggressive targets 
(e.g. <130 systolic for diabetes and 
chronic kidney disease)20,21.  The most recent AHA/ACC guidelines go further to recommend 
both pharmacologic and non-pharmacologic strategies to achieve a treatment target of 
<130mmHg for most patients22; although these recent guidelines have yet to achieve widespread 
Table 1: NLA treatment goals for PLHIV.  
Risk 
Category
Criteria 
NLA goal 
Non-HDL-C 
LDL-C 
Low 
N/A* 
N/A* 
Moderate 
2 major risk factors (i.e. HIV + high BP 
only) 
<130 mg/dl 
<100 mg/dl 
High 
 3 major risk factors 
<130 mg/dl 
<100 mg/dl 
Very High
Known ASCVD OR 
Diabetes + 2 major risk factors * 
<100 mg/dl 
<70 mg/dl 
Major risk factors include: HIV, Age >45 men or >55 women, family history of 
early CAD, smoking, hypertension, low HDL-C.  
* By design, all participants in our study will be > low risk and those with 
diabetes will be very high risk.
Figure 1: The extended HIV treatment and prevention cascade 

 
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implementation.  To achieve these targets, many will require more than one drug and a lifetime 
of titrating medication. Improving self-management is thus a critical component to successful 
treatment of blood pressure over time.23  
 
For cholesterol management, HIV-specific guidelines exist24,25; although, the National 
Lipid Association (NLA) recommendations25 are the only current guidelines from the modern 
ART treatment era. In 2015, the NLA Expert Panel on HIV recommended the NLA approach to 
risk stratification and target non-HDL-C and LDL-C goals26 (Table 1), with the additional 
recommendation that HIV infection may be counted as a major ASCVD risk factor for the 
purposes of risk stratification (Grade B recommendation, moderate quality evidence). Non-HDL-
C (total cholesterol – HDL-C) is recommended by the NLA as a surrogate measure of total 
atherogenic cholesterol and appropriate treatment target.26 Critics of cholesterol treatment targets 
refer to the 2013 ACC/AHA statin treatment guidelines27 that recommend moderate or high dose 
statins for four proven statin-benefit groups, citing limited randomized controlled trial evidence 
for non-statin therapies or cholesterol treatment goals. Subsequent clinical trials, however, have 
demonstrated that adding certain non-statin treatments such as ezetimibe28 or PCSK9 inhibitors29 
to statins reduces clinical events, supporting the notion that reductions in risk are generally 
proportional to reductions in atherogenic cholesterol.30,31   
The HIV workforce is changing.  Unfortunately, achieving ASCVD prevention targets 
in HIV specialty clinics is challenging in the face of increased clinical demands and a changing 
HIV workforce. Over the past 10 years, the HIV Medicine Association (HIVMA)32 and the 
Institute of Medicine33 have been warning of looming shortages of HIV specialists. Currently, 
58% of HIV providers fit the HIVMA definition of HIV specialist1, and numbers are projected to 
decrease due to high levels of dissatisfaction, just as attempts to improve the HIV treatment 
cascade bring larger numbers of patients into care1. Primary care providers (PCPs) may be able 
to fill the gap, but feel inadequately trained in HIV care.34 Similarly, HIV-specialists are often 
uncomfortable providing primary care, including high blood pressure and cholesterol 
management.9 Furthermore, HIV-providers who plan to leave practice in the next 5 years are 
more likely to provide primary care (90%) compared to those who do not plan to leave practice 
(83%) and those who just recently entered practice (77%, p=0.02).1 Treating higher numbers of 
HIV patients is associated with better HIV management and lower overall mortality35, but is not 
associated with better cholesterol treatment for ASCVD prevention.36  
Models that promote shared responsibilities between non-HIV providers and HIV-
specialists exist, but their effect on primary care and non-AIDS outcomes such as ASCVD has 
not been rigorously studied.37  Undoubtedly, changing patterns of care (i.e. shifting more non-
HIV prevention care to non-HIV providers) may require shifts in patient-provider trust and 
communication.  Because of longstanding relationships, many HIV patients fiercely trust their 
HIV provider for comprehensive care.9,38  Eighty-four percent of patients preferred having their 
HIV provider be their PCP9, and two-thirds of those with an outside PCP only had one because 
of an insurance company requirement. The impact of patient-provider trust and communication 
networks on ASCVD prevention efforts needs to be more formally evaluated among PLHIV.  
“I always thought I would die of AIDS”.  Is low perceived risk a barrier to high-
quality ASCVD preventive care?  Before effective combination antiretroviral therapy, most 
people with HIV infection died of AIDS-related causes, and cardiovascular disease prevention 
was not a priority for most patients and providers.  Yet, there is some evidence that low 
perceived cardiovascular risk persists even in the ART treatment era.  For example, perceived 

 
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CVD risk poorly correlated with Framingham risk scores (r=0.24) among PLHIV with 
longstanding infection (mean 15 years since HIV diagnosis) and history of lower nadir CD4+ 
count (mean nadir CD4+ 195)8.  The reasons for this poor correlation and the influence of 
perceived risk on ASCVD prevention behaviors are not known. 
Nurse-led interventions are highly effective in high-risk populations in the general 
population.  The use of non-physician providers (e.g. registered nurses, nurse practitioners, and 
physician assistants) is expanding in the US, a trend that is also true in HIV-specialist care.1,39  
The quality of HIV care provided by these non-physician specialists is comparable to physician 
specialists40, but the quality of and comfort level with ASCVD preventive care is poorly 
understood.  Our experiences in other US populations suggests that nurse-led management of 
cardiovascular risk factors is highly effective.10-12,14 Key features of our prior interventions 
include: (1) care coordination, (2) nurse-managed protocols and medication adherence 
counseling, (3) home blood pressure monitoring; and (4) integrated use of information 
technology tools such as EMR support. For example, home BP monitoring + behavioral 
counseling led to a 6mmhg reduction in systolic BP in one of our prior studies.12  Further, a 
meta-analysis of nurse-managed protocols showed clinically significant 4mmHg reduction in 
systolic blood pressure and 10-12 mg/dL reduction in cholesterol.41  In a meta-analysis of 
adherence interventions, reductions in cholesterol were even higher (15-20mg/dL).42 
 
3. Setting and Conceptual Framework 
The proposed study will be conducted at three Ryan White Program federally-funded 
academic medical centers that provide HIV specialty care for racially and ethnically diverse 
PLHIV that are broadly representative of the US HIV+ population (Table 2). The MetroHealth 
site is primarily urban, while 21% of UH patients and 28% of Duke Health patients are from 
rural counties. There is minimal overlap in HIV specialty care between Cleveland sites, with 
preliminary data suggesting <1% receive outpatient HIV care at both sites in a given calendar 
year. Case Western and Duke have Centers for AIDS Research (CFARs) and considerable 
support services to conduct HIV research. The Duke and University Hospitals sites are also 
AIDS Clinical Trials Group sites. Since 2013, PI Longenecker has run an HIV cardiology clinic 
twice monthly at the University Hospitals Special Immunology Unit HIV clinic, but his patient 
panel is focused on those with established CVD rather than prevention and risk factor 
management, highlighting a need for the proposed intervention. 
Table 2: Demographics of PLHIV engaged in care at the three academic HIV-specialty clinic sites selected 
for this study 
 
Total patients  Age (IQR) 
% Female 
% Black 
% Hispanic 
MetroHealth (Cleveland, OH) 
1759 
47 (35-55) 
24% 
50% 
13% 
Duke Health (Durham, NC) 
1890 
50 (40-58) 
28% 
59% 
4% 
University Hospitals (Cleveland, 
OH) 
1101 
51 (40-58) 
23% 
64% 
4% 
Study Team: Our team is highly qualified to carry out the aims of this study. The three co-Pis 
represent diverse disciplines and unique research expertise. Co-PI Longenecker is a cardiologist 
and K23-funded early stage investigator (Year 4) in transition to independence and has an 

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established track record of research on cardiovascular disease in HIV. Co-PI Bosworth is a 
senior and awarded PhD psychologist with extensive experience testing interventions to improve 
cardiovascular risk in vulnerable populations. Co-PI Webel is a PhD nurse scientist and mixed 
methods researcher who studies self-management of HIV and cardiovascular health among 
PLHIV. Our multiple PI structure combines the experience of a senior implementation scientist 
with the enthusiasm of two promising early stage HIV investigators. We also incorporate HIV 
specialists (Hileman and Okeke), cardiologists (Vedanthan and Bloomfield), and statistics and 
data management support (Smith). Our team has longstanding collaborations and a track record 
of publication together.43-54  
Conceptual Framework: Our study utilizes the RE-AIM implementation framework (Figure 2).  
As originally conceived by Glasgow et al55, RE-AIM stands for Reach X Efficacy—Adoption, 
Implementation, Maintenance, and captures the five factors that contribute to the public health 
impact of an intervention.  Abrams et al defined population impact as Reach X Efficacy56, and 
RE-AIM added the 3 additional components to further describe contextual factors that influence 
the reach and efficacy of an intervention.  We believe that if proven effective for ASCVD risk 
factor control, the concept of a prevention nurse specialist may be scaled-up to address a broad 
range of preventive care services for PLHIV, thus increasing its population impact. Our model 
may be especially relevant in the context of a changing HIV specialty workforce that will 
increasingly rely on non-physician providers and increased coordination with non-HIV primary 
care providers and specialists. Finally, the EXTRA-CVD intervention itself is grounded in two 
models of behavior change: (1) the information-motivation-behavioral skills model and (2) self-
regulatory theory.57-61 These models explain how health behavior change is mediated through 
self-monitoring (lifestyle change and medication adherence) and acknowledge the central role 
Figure 2: Conceptual framework for the EXTRA-CVD study 

 
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that self-efficacy plays in sustained behavior change62-64 (Figure 2 sidebar). 

 
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4. Objectives 
1. Conduct a baseline assessment of ASCVD preventive care and perceptions of ASCVD 
risk in the HIV specialty clinic environment. (Aim 1) 
2. Adapt the EXTRA-CVD intervention components to the HIV specialty clinic context 
with key stakeholder input and data from the baseline assessments (Sub-Aim 1.1) 
3. Evaluate the 12-month efficacy of the EXTRA-CVD intervention to improve BP and 
cholesterol control in PLHIV (Aim 2)  
4. Conduct a process evaluation of the EXTRA-CVD intervention (Aim 3) 
5. Evaluate the 12-month efficacy of an adapted virtual intervention to improve blood 
pressure in PLHIV 
 
5.  Hypothesis 
We hypothesize that our prevention nurse-led intervention will lead to a statistically 
significant reduction in systolic BP (primary) and non-HDL cholesterol (secondary) over 12 
months compared to those receiving general prevention education only. 
 
6. Study Design.  
Aims 1: Mixed-methods 
There are two groups of participants for this aim 
x PLHIV (n=60) 
x Healthcare team members (n=36). 
This mixed-methods aim will have two complimentary areas of focus: 
x Perceptions of ASCVD risk 
x Barriers to and facilitators of high-quality ASCVD preventive care 
We will recruit up to 60 PLHIV (n=20 from each site) to participate in a mixed-methods 
study. We will enroll until we achieve data saturation, where no new themes or explanations 
emerge. Based on previous work49,65-68, this sample size more than sufficient to reach 
saturation. All PLHIV will have suppressed HIV viral load (<200 copies/ml), hypertension 
(SBP >130mmHg on two occasions in the EMR within the last year and/or on anti-
hypertensive medication), AND hypercholesterolemia (non-HDL > NLA target (see Table 1) 
and/or on cholesterol medication). Additionally, up to 36 healthcare team members (3 HIV 
MDs, 3 PCPS, 3 RNs and 3 support staff members from each site) will complete a key 
informant interview. PLHIV and care team members will be recruited by purposive and 
snowball sampling from the clinics in which they receive care and work. All subjects will be 
consented prior to enrollment.  
Sub-Aim 1.1: Intervention adaptation  
We will use a participatory, iterative design process69-71 with a “design team” at Cleveland 

 
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(combined UH/Metro Design Team; ~12 members) and Duke (~6 members).  Design team 
members may include research team members, HIV providers, primary care providers, 
nurses, PLHIV with hypertension and hypercholesterolemia, information technology experts, 
and any other key stakeholders TBD. The design process will involve three main phases: 
brainstorming, conceptualization, and creation described below in study procedures. 
Additional acceptability and feasibility testing will occur before and after a 6 week pilot 
intervention.  These data will inform two additional design team meetings to iteratively refine 
the intervention. 
Aim 2: Randomized controlled trial 
HIV+ adult participants (n=300) on suppressive ART with both hypertension (confirmed 
systolic BP >130 mmHg and/or on treatment) & hypercholesterolemia (non-HDL cholesterol 
> National Lipid Association targets and/or on treatment) will be stratified by 3 clinic sites 
and randomized 1:1 to intervention vs. education control. 
Aim 3: Descriptive Process Evaluation 
We will conduct a process evaluation72 of the intervention focusing on the RE-AIM domains 
of reach, adoption, and implementation. We will evaluate key implementation process 
measures across the following domains: fidelity (quality), dose delivered (completeness), 
dose received (exposure and satisfaction), recruitment, reach (participation rate), and context 
with both PLHIV and health care team participants73,74 
Table 3: Summary of qualitative research methods by study population 
Population 
Target N 
Methods 
Aim 1: PLHIV 
60 
Focus group or interviews* 
Aim 1: Healthcare Workers 
36 
Interviews 
Aim 1.1: PLHIV Pilot participants 
9 
Focus group or interviews* 
Aim 1.1: Feasibility Testing (Healthcare 
Workers) 
9 
Interviews 
Aim 1.1: Design Team Members 
20 
Focus group 
Aim 3: Process Evaluation (PLHIV) 
30 
Interviews 
Aim 3: Process Evaluation (Healthcare 
Workers) 
36 
Interviews 
Aim 4: Design Team Members 
20 
Focus group or design meeting 
transcripts 
Aim 4: PLHIV 
24 
Interviews 
 
Aim 4: Virtual Intervention Adaptation and Hybrid Implementation-Effectiveness Study 
Intervention Adaptation 
The adaptation process will be similar to that described above for sub-aim 1.1, however, will be 
condensed into three sessions: one at-home preliminary activity and two Zoom videoconference 
meetings. At these meetings, several suggested virtual enhancements will be presented and 
design team members will engage in abbreviated exercises to (1) brainstorm, (2) conceptualize, 
and (3) create new virtual enhancements to the intervention. Small working groups will be 
assigned to further develop the enhancements into final products offline, using iterative 

 
Protocol 
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processes consistent with human-centered design principles 
Implementation-Effectiveness Trial 
In this hybrid type 3 implementation study, we will enroll (n=75) adult PLWH on suppressive 
ART with high BP whom are otherwise ineligible for the parent trial because they do not also 
have high cholesterol or because they are unwilling or unable to participate in the in-person trial. 
Participants will be stratified by the 3 clinic sites. Implementation outcomes based on a RE-AIM 
framework8 will be compared to parent trial participants: reach (% agreeing to 
participate), effectiveness (change in home systolic BP), adoption (frequency of home BP 
use), implementation (qualitative assessment of feasibility/acceptability), 
and maintenance (qualitative).   
 
7. Study Enrollment and Withdrawal 
Aim 1 Enrollment:  
There are two groups of participants for Aim 1, PLHIV and Healthcare Team Members. We 
will recruit PLHIV participants using an IRB-approved flyer describing the study and a number 
to call for information as well as by presenting at staff meetings and retreats. In addition, the 
Duke site will additionally use an IRB-approved recruitment letter.  We will recruit Healthcare 
team members at each study site by email and personal invitation, attempting to obtain a 
representative sample.  We will enroll 3 HIV MDs, 3 PCPS, 3 RNs and 3 support staff members 
from each site (see table) 
After a brief screening, potential subjects not meeting inclusion criteria will be thanked for 
their time and excluded from enrollment. Those meeting criteria (see table below) will be 
scheduled for the enrollment visit and interview.   
* Our inclusion criteria for PLHIV participating in aim 1 matches the enrollment criteria of 
PLHIV for aim 2, with the idea that we would like to recruit these same participants to enroll in 
the clinical trial portion of the study; however, this aim 1 study will be temporally separated 
from aim 2 and subjects will not be required to participate in both aims of the study.  The reason 
for this is to gather data on a broadly representative and generalizable sample of PLHIV with 
hypertension and hypercholesterolemia prior to intervention adaptation and implementation.     
* Our hypertension inclusion criteria reflect the definition of hypertension from the recently 
updated AHA/ACC Guideline for the Prevention, Detection, Evaluation, and Management of 
High Blood Pressure in Adults22.   

 
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Inclusion Criteria 
Exclusion Criteria 
PLHIV 
(n=60) 
1. Age 18 years 
2. Confirmed HIV+ diagnosis  
3. Undetectable HIV viral load: 
defined as the most recent HIV 
viral load <200 copies/mL, 
checked within the past year 
(assessed via chart abstraction)  
4. Hypertension: defined as systolic 
BP >130 mmHg on  2 
occasions in the past 12 months 
or on an antihypertensive 
medication (assessed via chart 
abstraction) 
5. Hyperlipidemia: defined as a 
non-HDL cholesterol >130 
mg/dL or on cholesterol lowering 
medication  
1. On lipid-lowering 
medication solely for 
secondary prevention of 
ASCVD events with 
evidence of pre-medication 
non-HDL which was 
already below 100mg/dL 
2. On anti-hypertensive 
medications solely for a 
non-hypertension 
indication (e.g. systolic 
heart failure) 
3. Severely hearing or speech 
impaired, or other 
disability that would limit 
participation in the 
intervention components 
4. In a nursing home and/or 
receiving in-patient 
psychiatric care 
5. Terminal illness with life 
expectancy < 4 months 
6. No reliable access to a 
telephone  
7. Pregnant, breast-feeding, 
or planning a pregnancy 
during the study period 
8. Non-English Speaking 
 
Healthcare 
team 
members 
(n=36) 
1. HIV specialist MD (generalist or 
infectious disease) with at least 1 
full day of outpatient 
clinic/week, OR 
2. Primary care provider who cares 
for >5 HIV+ patients in his/her 
panel, OR 
3. Registered nurse whose primary 
appointment is in an HIV 
specialty clinic, OR 
4. Support staff member at an HIV 
specialty clinic including but not 
limited to: medical assistant, 
receptionist, dietician, social 
worker, or pharmacist.  
1. PI or co-investigator on the 
study 
2. Non-English Speaking 
 

 
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Sub-Aim 1.1 Enrollment: 
There will be 2 design teams—one in Cleveland (~10-12 participants; combined UH and Metro) 
and one at Duke (~6-8 participants).  Each design team will be composed of willing participants 
recruited from the local clinics and may include research team members, HIV providers, primary 
care providers, nurses, PLHIV with hypertension and hypercholesterolemia, information 
technology experts, and any other key stakeholders.  The intervention design team process is not 
a research study; however, participants will be asked to participate in a research evaluation of the 
design process.  This will consist of a brief survey and a focus group discussion.  Potential 
participants for the survey and focus group discussions will be recruited at the design team 
meetings, but participation in the research component will not be a requirement for participation 
in the design team process.   
In addition, we will recruit up to 3 PLHIV at each clinic site (up to 9 total) to participate in a 6-
week pilot study of the intervention (all will be assigned to the intervention assessments as 
described in aim 2 for this pilot).  In order to provide feedback that will help refine the 
intervention further, these pilot participants will be asked to participate in focus groups and/or 
interviews before and after the pilot study.  These PLHIV will fulfill the same 
inclusion/exclusion criteria as for the randomized trial described in Aim 2.  They will be 
recruited in person from the patient panels of study investigators or HIV-specialty clinic 
colleagues (with their permission) at the time of their usual clinic appointments.  Because we are 
recruiting such a small number of subjects, we expect that we will not need any additional 
recruitment materials for this part of the study.   
We will also involve our local HIV Community Advisory Boards (CAB) at UH and Duke to 
provide feedback on our study during the design team process.  These CABS are routinely 
utilized in many HIV studies.  At the CAB meetings, our study staff will be taking notes about 
content themes and specific suggestions but the sessions will not be recorded and none of the 
recorded data will be associated with CAB member identifiers. Because there is no identifiable 
data being collected, we are asking for a waiver of consent for these CAB meetings. 
Finally, we will also conduct interviews of up to 18 health workers recruited from the HIV clinic 
sites (6 per site) who may have come into contact with the prevention nurse or pilot participants’ 
care during the course of the 6 week pilot.  Examples of such health workers may include: (a) a 
primary HIV doctor who is asked by the prevention nurse to add a new blood pressure 
medication, (b) an HIV nurse who interacts with the prevention nurse to coordinate care between 
HIV provider and PCP over a cholesterol management issue.  Potential participants in this part of 
the pilot evaluation will be identified through the course of the pilot intervention by the site 
prevention nurse and will be recruited from the clinics by the prevention nurse.  At all three sites, 
we intend to recruit these persons from clinic through in-person invitations to participate in a 
feasibility testing interview.  Once recruited, arrangements for an in-person consent and 
interview will be made.   
Aim 2 Enrollment: 
Pre-screening: We will use the electronic medical records at our three sites to identify 
potential subjects for our study according to the following inclusion/exclusion criteria (same as 

 
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aim 1 PLHIV, except for addition of exclusion criteria #8). Potential subjects will initially be 
mailed a recruitment letter signed by his or her primary HIV provider (or sent a message through 
MyChart at Duke site only, see below). Potential subjects will have the opportunity to opt out of 
the study by calling a toll-free number. We have used these same strategies in our previous 
studies.  
 
Inclusion Criteria 
Exclusion Criteria 
PLHIV 
(n=300; 
n=100 per 
site) 
1. Age 18 years 
2. Confirmed HIV+ diagnosis  
3. Undetectable HIV viral load: 
defined as the most recent HIV 
viral load <200 copies/mL, 
checked within the past year 
(assessed via chart abstraction)  
4. Hypertension: defined as systolic 
BP >130 mmHg on  2 
occasions in the past 12 months 
or on an antihypertensive 
medication (assessed via chart 
abstraction), and 
5. Hyperlipidemia: defined as a 
non-HDL cholesterol >130 
mg/dL or on cholesterol lowering 
medication  
1. On lipid-lowering 
medication solely for 
secondary prevention of 
ASCVD events with 
evidence of pre-medication 
non-HDL which was 
already below 100mg/dL 
2. On anti-hypertensive 
medications solely for a 
non-hypertension 
indication (e.g. systolic 
heart failure) 
3. Severely hearing or speech 
impaired, or other 
disability that would limit 
participation in the 
intervention components 
4. In a nursing home and/or 
receiving in-patient 
psychiatric care 
5. Terminal illness with life 
expectancy < 4 months 
6. No reliable access to a 
telephone  
7. Pregnant, breast-feeding, 
or planning a pregnancy 
during the study period 
8. Planning to move out of 
the area in the next 12 
months 
9. Non-English Speaking 
 
MyChart is the patient portal of the electronic medical record at Duke (Epic).  For 
patients that utilize Epic MyChart messaging at Duke, a Maestro Care MyChart recruitment 
invitation will replace the recruitment letter. The DOCR Maestro Care Analyst team is involved 
in implementing this process. Potential subjects who fit basic inclusion criteria are identified by a 
computer algorithm within the electronic medcial record (Epic) based on diagnoses, recent lab 
values, demographic information, and blood pressures. No person will review the medical record 
and no information will be shared with the research team prior to this message being sent.  If the 

 
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September 7, 2022 
 
message is received and read by the patient, he/she will indicate if they are interested or not 
interested and the study coordinator will be sent an In basket message (Maestro Care internal 
message) indicating the response. Only key personnel who are delegated the task of patient 
identification and recruitment will have access to the In basket messages. Patients who express 
interest or patients who do not respond will be contacted by telephone following the screening 
process described below. 
Screening: A research assistant will contact all subjects who do not opt out.  Following a 
telephone script, the research assistant will describe the study in detail, ensure the patient is 
eligible and willing to participate, and schedule a baseline study visit at the next clinical visit 
with an HIV provider where they will be enrolled following the informed consent process 
described below.  Study staff will make up to 3 attempts at telephone contact before marking a 
pre-screen eligible subject as “unable to contact.”  In person contacts may be made at scheduled 
clinic visits.  We will also seek to ensure that the contact information on file is correct by cross-
referencing other sources in the electronic health systems at each site.   
Finally, some patients may become aware of the study through their care team or word of 
mouth prior to receiving a pre-screening letter.  These patients will be encouraged to contact 
study staff for screening (same script as above).  In addition, a flyer will be posted at the Duke 
Infectious Diseases clinic as an additional avenue of recruitment.  Additional across the board or 
site-specific strategies may be considered in the future if recruitment is a challenge. 
We have previously estimated (2016 data; see table) that 900+ subjects in care at the 3 
study sites would meet our inclusion criteria and would be eligible for enrollment.  If we have 
trouble recruiting, we have access to additional community sites associated with our academic 
medical centers with similar demographics.  Minority populations will be enrolled. While this 
group is considered a vulnerable population, the study team has considerable experience 
enrolling these participants and adapting interventions that are culturally sensitive. Given the 
increased prevalence of ASCVD risk factors in these populations, it is important that they are not 
excluded from participation in this study. 
Table 4: Estimated eligible subjects at each clinic site based on 2016 data. 
 
HIV viral 
load <200 
Hypertension* 
Hypercholesterolemia* 
Both* 
MetroHealth 
1500 
(85% of all 
HIV+) 
491 
501 
26 
Duke 
1349 (71%) 
605 
397 
291 
University 
Hospitals 
975 (89%) 
550 
485 
334 
* Defined here as a billing code/chart diagnosis OR on anti-hypertensive or cholesterol 
medication.  The numbers for hypertension and hypercholesterolemia reflect ONLY HIV 
patients with HIV viral load <200 copies/ml.   

 
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Aim 3 Enrollment: 
Using the same methods as in Aim 1 (IRB-approved flyer and personalized invitations), random 
subset of n=30 intervention participants (10 from each of the three sites) and n=36 healthcare 
team members will be asked to complete key informant interviews. We will target the same 36 
care team members who completed aim 1 interviews but, due to staff turnover, it is possible we 
may enroll those who did not participate in Aim 1. 
An important process measure of Aim 3 is intervention dose, yet the total dose of complex multi-
component interventions is often difficult to conceptualize.  As part of a Diversity Supplement of 
the parent grant awarded to Dr. Angela Aifah, we will re-engage the design team members that 
have participated in sub-aim 1.1 and aim 4 intervention adaptations to participate in a 2-part 
process of constructing a composite measure of total dose as described below and in Appendix T.    
Aim 4 Enrollment:  
Intervention Adaptation  
Participants in the adaptation design team have already been identified as described in sub-aim 
1.1, and have participated in the adaptation of the aim 2 trial. All original 20 design team 
members agreed to be contacted for future research, and will therefore be invited to participate in 
the aim 4 intervention adaptation process. Those members who agree to participate in aim 4 will 
be consented virtually and sent an invitation to participate in two zoom meetings, as described in 
the study procedures section.  
Implementation-Effectiveness Trial 
The aim 4 implementation study will enroll 110 participants (n=35 at each site) in the virtual 
arm. We have previously estimated the number of eligible participants at each site (Table 
5). These numbers demonstrate the feasibility of our proposed new enrollment (~10x the 
enrollment goal).  
Table 5: Estimated eligible participants at each clinic site.  
  
High BP 
High Cholesterol 
Both* 
High BP only* 
MetroHealth  
491 
501 
286 
205 
Duke  
605 
397 
291 
314 
University Hospitals  
550 
485 
334 
216 
* Those with both conditions are eligible for the parent trial, and those with high BP only are eligible for 
the virtual arm.  
PLWH on ART with suppressed HIV viral load and high BP will be eligible to enroll in the 
virtual intervention arm if they are otherwise not eligible for the parent trial because they do not 
also have high cholesterol. In addition, any patient who would otherwise be eligible for the 
parent trial, but who is unwilling or unable to come to the clinic site for in-person visits would be 
offered an opportunity to enroll in the virtual arm. These data will be captured in our detailed 
screening and enrollment form. The inclusion and exclusion criteria will otherwise remain the 
same as the parent trial, including access to a telephone. Access to a computer or smart 
phone with video camera teleconferencing capabilities will not be required, but will be closely 

 
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tracked and high levels of support for using these technologies will be provided as described 
below. Data from our sites indicate that over two-thirds of participants will have access to 
videoconferencing technology.    
Participants for this virtual intervention arm of aim 4 will be screened and recruited through the 
same methods described in aim 2 if they meet aim 2 eligibility criteria 1-4. In addition, those 
participants identified as eligible for aim 2 but are unable or unwilling to enroll in the parent 
study due to issues related to access, will also be invited to enroll in this virtual arm through the 
same methods described in aim 2.  
Additionally, since this trial is focused on implementation outcomes, each site will include a 
subset of interested parent trial (aim 2) participants. Each site will aim to enroll at least five but 
no more than ten participants who have completed the aim 2 trial.  The goal is to gather enough 
data to determine if the aim 4 virtual intervention provides support to participants in 
maintaining and perhaps improving upon their blood pressure management achieved in the 
parent trial.    
 
Inclusion Criteria 
Exclusion Criteria 
PLHIV 
(n=110; n=35 
per site) 
1. Age 18 years 
2. Confirmed HIV+ diagnosis  
3. Undetectable HIV viral load: 
defined as the most recent HIV 
viral load <200 copies/mL, 
checked within the past year 
(assessed via chart abstraction), 
and   
4. Hypertension without 
hyperlipidemia (both defined in 
parent trial), or 
5. Hypertension and hyperlipidemia 
but unable/unwilling to enroll in 
the parent trial. 
6. Previously enrolled in the parent 
trial and interested in improving 
hypertension management 
through a virtual format. 
 
Same as parent trial criteria 
outlined in aim 2. 
 
Withdrawal: 
Throughout all phases of our study, subjects will be encouraged to complete the full course of 
the study assessments.  However, it is understood that a subject may discontinue study 

 
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participation at any time for any reason. The reason for early withdrawal must be documented in 
the subject’s case file and in the subject tracking document.   
Reasons for Withdrawal: Subjects are free to withdraw from the study at any time for any 
reason. Subjects should normally be withdrawn from the trial if a serious adverse event (SAE) 
occurs.  Subjects must be withdrawn from the trial if: 
 
1. They withdraw their consent; 
2. The investigator considers it in the best interest of the subject that he or she is 
withdrawn; 
The reason for any subject’s discontinuation and the date of withdrawal will be recorded in the 
subject’s case file.  The subject’s case file, which will be completed up to the point of 
withdrawal, will be retained for three years.  The study report will include reasons for subjects’ 
withdrawals as well as details relevant to the subjects’ withdrawals.  Any subject withdrawn 
from the trial prior to completion will undergo all procedures indicated in this protocol as being 
scheduled to occur at discharge or upon early withdrawal.  Any subject withdrawn due to an 
adverse event (whether serious or non-serious) or any clinically significant abnormal laboratory 
test value will be evaluated by the Principal Investigator or a monitor (see Key Personnel), and 
will be treated and followed up until the symptoms or values return to normal or acceptable 
levels, as judged by the Principal Investigator.  Relevant post-study procedures will be 
performed, wherever possible, on subjects who elect to withdraw.   
Handling of Withdrawal: If a subject is withdrawn from participation in the study at any time at 
his or her request, at the IRB or Principal Investigator’s discretion, the reason(s) for 
discontinuation shall be documented thoroughly in the source documents and subject’s case file. 
If a subject is discontinued because of an adverse event, this event will be followed until it is 
resolved or the subject is clinically stable and will also be documented in the source documents 
and the subject’s case file. 
. Study Procedures 
Informed consent:  
Subjects for each aim will give informed consent to participate in the project.  Research 
Assistants will read, review, and discuss consent forms with all potential participants prior to 
asking them to sign. If the candidate appears confused or indicates a lack of understanding, the 
interviewer will attempt to identify the misunderstanding and to explain the form again. Any 
candidate who still does not comprehend the form will be excluded from the study. We will ask 
questions to confirm understanding of the material covered in the consent procedure, both open-
ended (e.g., “Could you tell me what’s going to happen if you enroll in the study?”) and closed 
(e.g. “Will you get free medications from the staff of this research study?” or “what will happen 
to your medical care after the study?”). Persons who understand the consent form and agree to 
participate in the study will be asked to sign an authorization for the release of medical 
information to us. Interviewers will witness and date the signed forms and complete the 
corresponding. An informed consent checklist will be used to document the participant’s 
understanding of the informed consent process. Consent procedures will take place in a private 
room or office. Consent forms will be kept in a locked file cabinet within a locked room. 
For sub-aim 1.1, we will consent pilot participants once prior to acceptability testing 

 
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interview/group discussion and this consent will cover the entire pilot process (acceptability 
testing, pilot trial procedures, and feasibility testing).  For this sub-aim 1.1, we will also be 
soliciting feedback on the trial design from local HIV Community Advisory Boards (CAB) at 
UH and Duke as described above.  Because there is no identifiable data being collected, we are 
asking for a waiver of consent for these CAB meetings. 
For aim 1 and sub-aim 1.1, some interviews at the Duke site will be conducted by 
telephone in order to reduce barriers to enrollment and therefore obtain the most representative 
sample possible.  These phone consents will be scripted (see separate IRB-approved scripts for 
Aim 1 and sub-aim 1.1), adhering to the same general consent process described above.  Phone 
consents will NOT be performed at UH or MetroHealth sites, because travel is less of a barrier 
for these clinic populations. 
For aim 2, a partial waiver of consent is requested for pre-screening and chart review 
procedures as described. Once the subject is screened and agrees to enroll, then informed consent 
will be obtained at the baseline visit. Prior to the baseline visit, in order to streamline data 
collection for the participant and study staff, the study staff will perform a chart review of the 
participant’s medical history.  Medical history obtained from chart review will be verified with 
the participant on the day of the baseline visit.  Our rationale is that we anticipate a low risk for 
loss of confidentiality during pre-screening and chart review procedures.  In addition, waiting to 
perform the chart review together with the participant on the day of the procedure would 
considerably lengthen the study visit, which would inconvenience the participant.  If, in the rare 
case that a qualified participant agrees to participate and is scheduled for a baseline visit, but 
then fails to attend the baseline visit and decides not to reschedule prior to signing informed 
consent, then any information collected by chart review will be deleted from the study database.   
 
We plan to obtain verbal consent to record the following demographic variables for all 
persons that agree to be screened in person or by phone, but who ultimately decline to 
participate: (1) age, (2) sex, (3) gender identity, (4) race/ethnicity.  Thus, at the end of the trial, 
we will be able to document whether those who declined to participate are different 
demographically than the population of patients who agreed to enroll.  This is important to 
describe the generalizability of our study findings.  Verbal consent will be documented in 
RedCap. Verbal consent will also be obtained and documented for scheduling and documenting 
participants’ baseline visits in participants’ Electronic Medical Records at Duke Health.  
 
For the aim 4 intervention adaptation, the 20 original design team participants who 
agreed to be contacted for future research in the consent form for sub-aim 1.1 will be invited to 
participate in the aim 4 virtual design sessions. These design team members agreed to be 
contacted and engage in communication with study team members via e-mail during sub-aim 
1.1. To invite design team members to participate in aim 4, the study team coordinators at each 
site will send an e-mail to members explaining the purpose and procedures of the adaptation 
activities. This e-mail will include a REDCap survey link to a form that will capture the 
participant’s interest in participating in or declining the invitation to aim 4. For those that 
decline, the REDCap survey will end, thanking the member for their time. For those that are 
interested in participating, the REDCap survey will inform the design team member that a study 
team member will need to contact them to complete the informed consent process, and the 
survey will capture the preferred communication method to schedule that virtual visit (e-mail or 
phone contact information). A study team member will then contact the design team member 

 
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through phone or e-mail to schedule the virtual informed consent visit and explain the process. A 
study team member will email a REDCap survey link to the full version of the consent document 
to the participant on the scheduled date. This virtual consent will capture an electronic signature 
and follow most of the guidelines laid out by the UH IRB in their document titled Guidelines for 
Remote Electronic Consent. An exception will be the audiovisual visit to confirm identity, as the 
study team has determined that this will place unnecessary burden on the design team members. 
All design team members have worked closely with the study team during sub-aim 1.1 and their 
identity is well-known to the study team. Aligning with data captured from participants during 
sub-aim 1.1, the study team member will ask the participant for their full name, professional title 
at their respective site, and their e-mail address to confirm their identity over the phone, and will 
then perform verbal informed consent while the participant reads along through the REDCap 
survey link. The participant will select in REDCap whether or not they would like to be 
contacted for future research, how their data may be used, and will provide their electronic 
signature confirming their consent to participate. The design team sessions will take place via 
Zoom videoconference, and these sessions will be recorded for the purpose of qualitative data 
analysis. Using a recording disclaimer function available in Zoom, attendees will be prompted to 
provide their consent to be recorded before entering the Zoom session. If the participant agrees, 
they will enter the Zoom session, and if they decline, they will not be able to enter the Zoom 
session. Neither sub-aim 1.1 nor aim 4 discuss or share confidential information through e-mail 
or in-person meetings. The only participant level data that will be collected from design team 
members is demographics, which will be collected after they consent through a REDCap survey 
link. That link will also include an organizational readiness assessment for those whose 
professional role is within the study site HIV clinic. Design team Zoom activities are centered 
solely on the intervention design and study implementation procedures, and therefore the Zoom 
videoconference will not put design team participants at risk for disclosure of PHI or other 
sensitive information. 
 
For the aim 4 implementation-effectiveness trial, the consent process will be the same as 
that described in aim 2, save for the five to ten participants at each site who were enrolled in the 
aim 2 parent trial who will be able to consent virtually through REDCap, described below. The 
in-person consent visits for the participants who were not in the aim 2 trial, will be coordinated 
alongside existing clinical care at every opportunity to minimize the need for the participant to 
make additional trips outside of their home during the COVID pandemic. The participant will be 
seen only briefly during the consent visit to carry out the informed consent procedures and to 
provide the participant with the blood pressure cuff and education for home blood pressure 
monitoring. Verbal consent will be obtained and documented for scheduling and documenting 
participants’ consent visits in participants’ Electronic Medical Records at Duke Health. Pre-
baseline visit medical history chart review will follow procedures described in aim 2. Missing 
data from chart abstraction will not be attained until the second virtual study visit rather than the 
in-person consent and baseline visit. The reason for this is to minimize the length of the in-
person visit given that this is an intervention to test the effectiveness of virtual implementation of 
the EXTRA-CVD blood pressure management.  
 
Consenting the former aim 2 participants virtually is preferred over in-person in order to 
reduce face-to-face contact during COVID-19 and optimize the study team and participant 
engagement experience through virtual means, which is a key element of aim 4. These 

 
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participants have consented in-person in the past for aim 2, built a relationship with study team 
members, and will already have the blood pressure cuffs that necessitate the in-person consent 
visit for other participants who were not a part of aim 2. For those aim 2 participants interested in 
enrolling in aim 4, the study team member will schedule a time to conduct the informed consent 
process with the participant using the participant’s preferred remote method of communication 
(e.g. phone, videoconference). The study team member will offer to send a hardcopy of the 
consent document to the participant’s mailing address if the participant would like to review the 
document before the virtual consent meeting. On the scheduled consent date, the participant will 
be sent a unique link to the full consent document in REDCap. Before the informed consent 
process begins on the scheduled date, the study team member will confirm the identity of the 
participant by one of two ways. 1. If the participant has robust Internet access and a computer 
device, the participant will send a picture of their government issued picture ID to the study team 
member’s UH, Duke, or Metro email or sending the image through short message service (SMS) 
to a secure study cell phone (registered with the research institution). 2. If the participant can 
only communicate virtually through telephone without SMS or reliable Internet, the study team 
member will ask them to provide their full name, date of birth, and medical record number and 
compare the provided information to their medical record. These participants are already known 
to our study teams at each site, and have communicated throughout the aim 2 trial with the study 
nurses and coordinators. We believe this second option is more than sufficient in confirming the 
identity of participants with whom the study has already gained familiarity. This virtual consent 
will capture an electronic signature and follow most of the guidelines laid out by the UH IRB in 
their document titled Guidelines for Remote Electronic Consent, save the exception stated above 
(identity confirmation option 2). The participant will select in REDCap whether or not they 
would like to be contacted for future research, how their data may be used, and will provide their 
electronic signature confirming their consent to participate.  
 
Finally, we will also use remote electronic consent procedures identical to the aim 4 
intervention adaptation to re-consent Design Team participants to participate in a two part 
process to determine a stakeholder informed composite measure of intervention dose.   
 
Aim 1 Procedures: 
PLHIV (n=60): After signing informed consent, all PLHIV participants will complete the 
following assessments:  
1. A self-reported survey consisting of demographics, HIV and medical history, perceptions 
of CVD Risk (Appendix A; Health Beliefs for Cardiovascular Disease Scale75), and 
Adherence to Cardiovascular Medications (Appendix B Adherence to Hypertension and 
Cholesterol Medication Scales);  
2. A standardized interview of their family history of CVD; and  
3. An in-person interview discussion on perceptions of ASCVD risk and barriers/facilitators 
of ASCVD preventive care (see below). Medical chart abstraction will be used to 
determine history of use, adherence to, and tolerance of proven CVD prevention 
therapies. 
Key Informant Interviews (PLHIV). Prior to enrolling across all three sites, we will first 
pilot test an interview guide (see Appendix C) on 3-5 PLHIV in Cleveland and revise it 
accordingly. The final guide will be used to direct subsequent interviews consistently across 

 
Protocol 
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sites. The in-person interviews will take place at a secure, mutually agreed upon location. 
Questions will address the participant’s perceptions of ASCVD risks associated with HIV, risks 
associated with HIV medications, and CVD risk reduction measures. Additionally, we will 
assess barriers to and facilitators of improved ASCVD prevention.   
All interviews will take approximately 30 minutes, and audio recordings will later be 
transcribed verbatim. The interviews will be conducted by Dr. Webel or a trained qualitative 
researcher at the study site.  Dr. Webel has over 10 years of experience designing, implementing, 
and analyzing data from qualitative research studies.49,65-68 She has also successfully trained and 
managed qualitative data collectors and obtained high-quality data.49,67 
Healthcare team members (n=36): After signing informed consent, all healthcare team member 
participants will complete the following assessments:  
1. A self-reported survey consisting of demographics, training, and general practice 
patterns 
2. An in-person interview discussion on perceptions of ASCVD risk among patients 
with HIV in general (see below) and barriers 
 
Key Informant Interviews (Healthcare Team members). In a similar fashion to the PLHIV 
interviews, we will conduct individual in-person interviews to understand care team members’ 
perceptions of their patients’ ASCVD risk and how those perceptions influence the care they 
provide (i.e., decision to screen PLHIV for high cholesterol, knowledge of ASCVD prevention 
guidelines, when to refer to specialists, how they treat CVD risk factors, and the individual CVD 
risk reduction counselling they provide PLHIV). We will pilot test a key informant guide and 
revise it accordingly. The final guide will be used to direct the key informant discussions 
consistently across sites and ensure we have covered all relevant topics. These ~30 minute 
interviews will take place in a private room chosen by the staff member, and audio recordings 
will later be transcribed verbatim. Care team members will also complete a basic demographic 
form and information about their practice setting. 
Outcomes and analysis: Quantitative data (e.g., demographics, medical history, perceptions of 
CVD risk) will be summarized and used to describe the study samples. After redacting all names 
and identifying information, verbatim transcriptions of recorded interviews will be entered into 
Dedoose76, a secure, website-based analysis program to analyze qualitative data. A quality 
assurance protocol will be built into data management and analysis; 25% of the transcripts will 
be check to verify accuracy of the transcriptions and 10% will be double-coded to ensure inter-
coder reliability of 80% or greater. Pooled Kappa statistics will be calculated for codes to assess 
inter-rater agreement.77   
Under PI-Webel’s direction, all responses will be analyzed using standard analytic 
techniques for qualitative data: identification of themes/domains; coding or classification of 
participants’ responses by these themes performed independently by two team members (who 
have graduate-level training in qualitative coding); resolution of any coding discrepancies will be 
done by a third team member.78 To ensure consistency, a codebook and dictionary will be 
developed to create universal definitions for each code. The codebook will contain all codes, 
their definition, and exemplar quotes.  
For ASCVD risk perception, we will search for (a priori) codes that describe how 
perceptions of ASCVD risk are influenced by HIV and how that perception influences ASCVD 

 
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preventative care and behaviors. Significant inductive (emerging) codes will also be identified. 
Coded items will be grouped together into distinct themes. Group analysis meetings will be held 
to compare independently-developed codes for similarity and further direction. Once the 
codebook is developed and verified, all transcripts will be coded. Finally, the analytic team will 
work from the coded data to merge findings into a final report to aid the EXTRA-CVD 
intervention adaptation (sub-aim 1.1).38,65,79 This method of data reduction encompassing a 
multidisciplinary team-based analysis creates a robust iterative process through which the data 
are thoroughly discussed and analytical consensus achieved.  
 
For barriers and facilitators of ASCVD preventive care, we will search for a priori 
codes related to 1) Patient Facilitators: a) Health Beliefs, b) Health Priorities, c) Social 
Influence and Support, and d) Care Team Factors; 2) Patient Barriers: a) HIV-related factors, b)  
Health Beliefs, and c)  Health/ CVD knowledge; 3) Care Team Facilitators: a) Care Team 
Factors, b) Research/Guidelines, and c): Patient Factors; and 4) Care Team Barriers: a) Visit 
Logistics, b) Knowledge/Comfort, and c) Patient Factors. Significant inductive (emerging) codes 
will also be identified. Coded items will be grouped together into distinct themes and will be 
used to prepare a report of findings to aid in the EXTRA-CVD intervention adaptation. 
* For all interviews conducted by telephone at the Duke site, the participant will respond to 
survey questions on risk perception and medication adherence that are read over the phone.   
Clinic Variables Checklist: 
During the Aim 1 baseline assessment, investigators from each study site will complete a clinic 
variables checklist (Appendix D) in consultation with the site clinic director.  This form will 
characterize site-specific factors that may influence the results of all three aims of this study.  
These data will be used to characterize contextual aspects of effect modification by site.   
Sub-Aim 1.1 Procedures: 
The EXTRA-CVD Human-Centered Design process: 
We will use a participatory, iterative design process with two “design teams” (one team from 
Duke and another team consisting of both study sites in Cleveland combined), representing key 
stakeholders from each geographical site. For the purposes of this study, the design process will 
involve three key phases: Brainstorming, Conceptualization, and Creation and two additional 
meetings to refine the intervention for the acceptability and feasibility before the trial begins – 
making it a total of 5 sessions for this iterative design process.  For both Design Teams, a focus 
group discussion on the human-centered design experience will be conducted at the end of the 
final or fifth design team meeting among those who consent to participate.  
Aims of the EXTRA-CVD Human-Centered Design Process 
This human-centered design process has been adapted specifically for the EXTRA-CVD nursed 
led intervention as noted in Sub-Aim 1.1 of the study aims, i.e. to adapt the intervention within 
HIV clinic contexts through an iterative approach of collaborative meetings with key 
stakeholders. The following aims have been developed for this human-centered design phase:  
Aim 1: Refine the nurse-led intervention using the human-centered design approach with 
key stakeholders input.  
Aim 2: Evaluate the acceptability of the nurse-led intervention through semi-structured 
interviews or focus group discussions with PLHIV and HIV community advisory boards 

 
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Aim 3: Conduct a pilot study of the intervention and assess the feasibility as well as 
perceptions of the intervention with those involved in the pilot study through semi-
structured interviews and focus group discussions. 
Aim 4: Assess the reflections of the design team members on the human-centered design 
process though survey and focus group discussions. 
 
Initial Meetings: This intervention adaptation aim or human-centered design process will 
involve three initial phases: brainstorming, conceptualization, and creation: 
During brainstorming (Meeting #1), the design team will review the mixed-methods de-
identified data obtained during the baseline assessment on perceptions of ASCVD risk and 
barriers to and facilitators of ASCVD preventive care. The team will discuss these findings 
and brainstorm ideas to refine the EXTRA-CVD intervention in response to these data. 
Importantly, the design team will also review all data elements to be collected during the 
intervention in order to conduct the comprehensive process evaluation (aim 3). Possible 
targets for intervention adaptation include: (a) adjusting when, where, and to whom the EMR 
alerts appear; (b) adapting the treatment algorithms to overcome barriers and maximize the 
facilitators; (c) targeting the staff training to include relevant aspects of perceived risk into 
the care coordination and adherence support; (d) developing and tailoring staff training to 
facilitate acceptance, uptake, and effectiveness; and (e) helping us to quickly identify and 
troubleshoot any problems with the implementation of the intervention.  
x At Design Team Meeting #1, design team participants will be recruited to participate 
in a research study that evaluates the design process.  The research assessments will 
be a brief survey completed at this initial meeting and a focus group discussion during 
meeting #5 described below.   
In the conceptualization phase (Meeting #2), the team will evaluate advantages and 
disadvantages of ideas generated during the brainstorming, and will develop concrete 
changes to the intervention. For example, if team decides to include the name of the provider 
(PCP or HIV specialist) responsible for BP and cholesterol management on the EMR 
dashboard, the IT representatives will discuss its feasibility followed by a discussion of pros 
and cons. Final decisions will be made by majority vote of the design team; however, the 
study PIs may decide to veto modifications deemed to be counterproductive or an inefficient 
use of resources.  
The creation phase (Meeting #3) will involve the creation of refined treatment protocols, 
manuals of procedures, and educational materials.  
After the first three phases, there will be two Iteration meetings that will take place during the 
acceptability and feasibility phases.   
Acceptability Testing: Acceptability testing80 will be accomplished in 2 settings: (1) key 
informant interviews or focus group discussions with PLHIV pilot participants (2-3 per site, up 
to 9 total) and (2) HIV Community Advisory Board (CAB) meetings at UH and Duke.   
Key informant interviews or focus group discussions with PLHIV pilot participants will take 
place at local clinic sites and will be conducted in a similar fashion as described in Aim 1.  Each 
interview or focus group discussion will last for roughly 60 minutes and include participant’s 

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perceptions and experience navigating the HIV care system as a user or a provider.  The 
interview/discussion guide (Appendix E) will include the following elements: thoughts on HIV 
and CVD care and management; facilitators and barriers of implementing the nurse-led 
intervention within the clinic setting; and logistical factors (i.e. resources or tools at that clinic) 
that may or may not facilitate the integration of the intervention.  Data will be analyzed in 
Dedoose in a similar fashion to Aim 1 described above.   
Study investigators will present the intervention to a CAB meeting after the third design team 
meeting to further assess acceptability.  The CAB meetings are held monthly at UH and at Duke; 
there is no CAB at MetroHealth but some MetroHealth patients attend UH CAB meetings.  A 
research assistant will attend and take notes on the content themes and specific suggestions 
discussed, but there will be no personal identifying data collected.   
* Design Team Meeting #4: After the acceptability testing is completed, the design team will 
meet again (meeting #4) to discuss initial feedback on acceptability from pilot participants and 
CAB and to refine the intervention as needed.   
Pilot Trial: A 6 week pilot of the intervention will be conducted among 2-3 participants per site 
(up to 9 total).  The pilot trial procedures are summarized graphically as follows: 
 
 
At each of the two pilot study visits (week 0 and week 6), the PLHIV pilot participant will 
complete all study assessments as described in Aim 2 below.  In addition, at the time of the week 
6 follow-up visit, the participants will participate in an exit interview or focus group discussion 
about the feasibility of the intervention as described below.  All pilot participants will be able to 
keep the BP monitor after completion of the study.   
The time-frame of the pilot is compressed compared to the overall trial described in Aim 2 
below; however, there will be ample opportunity over 6 weeks to make sure that participants are 
able to use the home blood pressure monitors appropriately, that the telephone interaction with 
the prevention nurse is adequate, and that the medication treatment algorithms work smoothly.  
At a minimum, the prevention nurse will call once at the half-way point (~2-3 weeks) to “check-
in” about home blood pressure values and medication issues. 
Feasibility Testing: After the pilot study is completed, all PLHIV pilot participants will 
participate in either a focus group discussion or semi-structured interview depending on patient 
preference and logistical considerations (scheduling, availability of research staff, etc…).  The 
purpose of these interviews/discussions will be to explore the feasibility of the intervention. The 
interview/discussion guide for PLHIV pilot participants can be found in Appendix F.  The 
discussion will last 30-60 minutes and will focus on participants’ perceptions of the nurse-led 
Visit 1 (Week 0):
Meet Prevention 
nurse to discuss the 
care plan, take 
surveys, blood 
pressure and 
cholesterol checks.  
Focus Group:
A discussion about 
the EXTRA-CVD 
intervention with 
other patients in the  
pilot study 
 
Visit 2 (Week 6):
Surveys, blood 
pressure and 
cholesterol check.  
Exit interview or 
group discussion. 
Telephone 
contact with 
nurse 

 
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intervention and the facilitators and barriers of the intervention that may impact the sustainability 
of the intervention.   
Additionally, after the pilot is completed, up to 18 healthcare workers (6 per site) who have in 
some way been exposed to the pilot intervention will be recruited to participate in semi-
structured interviews for feasibility testing.  Examples of such health workers may include: (a) a 
primary HIV doctor who is asked by the prevention nurse to add a new blood pressure 
medication, (b) an HIV nurse who interacts with the prevention nurse to coordinate care between 
HIV provider and PCP over a cholesterol management issue.  Each interview will last 30-60 
minutes and will focus on the following elements: general thoughts on HIV and CVD care and 
management; perceptions of the nurse-led intervention; and the facilitators and barriers of the 
intervention that may impact the sustainability of the intervention.  The interview guide for 
health worker feasibility testing can be found in Appendix G.   
All qualitative data from this feasibility testing will be analyzed in a similar fashion as described 
in Aim 1.   
* Design Team Meeting #5: After the feasibility testing is completed, the design team will meet 
for a final time (meeting #5) to discuss feasibility testing results and refine the intervention as 
needed.  At this meeting, the design team members who have given consent to participate in a 
focus group discussion will reflect on the design process.  The discussion guide can be found in 
Appendix H.  This discussion will be recorded and the qualitative data will be analyzed in a 
similar fashion as described above.  
*** After the intervention adaptation design team process is fully completed, any changes to 
the protocol suggested by the design team will be submitted to the IRB for approval prior to 
starting the Aim 2 clinical trial.  The August 2019 modification contains these adaptations to 
aim 2 procedures as described in the Aim 2 procedures section below. 
Additionally, in Q4 of 2022, the Design Teams from Cleveland and Duke will be invited to 
participate in a 2-part process to formulate a composite measure of intervention dose.  The 
protocol and manual of procedures for this study was developed in detail by Dr. Angela Aifah 
(NYU) who will lead this part of the study with funding from her Diversity Supplement 
application.  The full protocol is available in Appendix T.  In brief, participants will participate 
in the following procedures: 
x Part 1: Group concept mapping: Each participant will be sent a unique link from study 
investigators to create an on online account at for the GCM portal 
(https://groupwisdom.com/groupconceptmapping).  Through this application, the 
participants will complete the following steps of answering questions in response to 
various prompts. The total duration of steps 1-4 + 6 is expected to take a total of ~1.5-2 
hours and does not have to be completed all at one time. 
o Step 1 - Preparation 
o Step 2 - Generation 
o Step 3 - Structuring 

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o Step 4 - Representation 
o Step 5 - (see below) 
o Step 6 – Utilization 
x Group concept mapping Step 5 – Interpretation: This step will be completed during a 
1-hour Zoom call so that all participants will be able to work together to interpret the 
results of steps 1-4. 
The 6 steps of group concept mapping are shown in the Figure below.  The outcome of the group 
concept mapping phase will be a shortlist of individual variables that participants believe best 
represent the dose of the intervention delivered by the EXTRA-CVD and AAIM-HIGH 
interventions.   
x Part 2: Delphi Process: This part of the study will further refine the list of variables 
generated during the group concept mapping phase to create a final composite measure of 
dose that incorporates different weights given to variables based on what stakeholders 
believe to be the most important aspects of the intervention.  There will be 3 rounds of 
questionnaires to complete online and the total time required will be ~30-45 minutes. 
The final composite measure of dose that results from this process will be used in analyses as a 
potential mediator of EXTRA-CVD outcomes, including both primary and secondary clinical 
outcomes (BP & cholesterol) but also implementation outcomes and other outcomes of interest 
(i.e. time to disengagement for those who are lost to follow-up).  
Aim 2 Procedures:
We will conduct a randomized controlled trial of the EXTRA-CVD intervention vs. 
education control among PLHIV on suppressive ART who have both hypertension and 
hypercholesterolemia. Control participants will receive general prevention education. The 
intervention—contextually adapted during sub-aim 1.1—will consist of prevention education 
plus 4 additional evidence-based components: (1) nurse-led care coordination, (2) EMR alerts 
and decision support, (3) home BP monitoring, and (4) nurse-managed medication 
protocols and adherence support. The primary outcome is change in systolic BP and the 
secondary outcome will be change in non-HDL cholesterol. Separately for hypertension and 
hypercholesterolemia, we will then examine changes in the three extended treatment cascade 
categories [(1) % appropriately diagnosed, (2) % appropriately managed, and (3) % at treatment 
goal]. We chose BP as the primary outcome because the EXTRA-CVD intervention components 

 
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were designed primarily to address BP management, with cholesterol management being an 
important but secondary consideration.  For the purposes of determining cascade level #1, we 
will use the following table to search for diagnosis of high cholesterol or blood pressure in the 
medical record.  
Table: Diagnosis terms for high cholesterol and high blood pressure for the purposes of determining 
cascade category from chart review.   
High Cholesterol 
High Blood Pressure 
Hyperlipidemia 
Hypertension 
Dyslipidemia 
Essential Hypertension 
Hypertriglyceridemia 
Secondary Hypertension 
Hypercholesterolemia 
Hypertensive end-organ disease  
Elevated LDL  
High blood pressure 
Elevated Triglycerides 
 
Elevated Cholesterol 
 
Familial Hypercholesterolemia 
 
 
 
DO NOT include the following: 
DO NOT include the following: 
Low HDL 
Pulmonary hypertension 
 
Intracranial hypertension 
 
Venous hypertension 
 
Pre-eclampsia or Maternal Hypertension 
 
Portal hypertension 
 
Ocular hypertension 
 
Randomization: Prior to study start, Dr. Smith will develop a 1:1 blocked randomization 
scheme, stratified by site.  This randomization scheme will be carried out using the 
randomization module in RedCap.  Participants will be randomized by RedCap at the time of 
their baseline visit to avoid randomizing participants who have not yet completed consent.  
Education control group: Participants assigned to the education group will receive usual care 
enhanced with general prevention education delivered by the prevention nurse. This active 
comparator is appropriate because participants have multiple risk factors for ASCVD, and 
advisory committees for prior studies have recommended this for similar study populations. The 
prevention educational modules will be delivered at 4 in-person visits (enrollment, 4, 8, and 12 
months), and will consist of evidence-based material on diet, exercise, smoking, sexually 
transmitted infections, and cancer prevention. As recommended by the design teams, control 
participants will have access to a wide range of educational materials about healthy living, but 
will not receive additional counseling from the prevention nurse outside of the 4 in-person visits.   
All participants in both intervention and education control arms will complete the following 
study assessments: 1) in-office BP obtained by a trained research assistant blinded to study group 
using a standardized protocol12 (0, 4, 8, 12 months); 2) lipid profile (0, 4, 8, 12 months); 3) 
perceived ASCVD risk survey56 (0, 12 months); 4) provider trust and communication survey (0, 
12 months). Study visits will be calculated from the date of the baseline enrollment visit in 
months.  Per protocol, study visits must be completed +/- 14 days from the calculated visit date.  

 
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Visits done between 14 and 28 days after the calculated visit date will be considered a protocol 
deviation.  Visits outside of the +28 day window will not be scheduled and that visit will be 
considered missing for that patient.  The fasting lipid panel blood draw will be done at the time 
of study visit or within a +/- 10 day window.  To limit potential bias, participants, their 
healthcare providers, and the prevention nurse delivering the education modules will be blinded 
to the in-office BP outcome measure unless a safety threshold is exceeded (systolic BP <90 or 
>180mmHg).  BP may be re-checked separately as part of routine care. 
Control participants will be encouraged to maintain participation in the study in order to 
minimize differential loss-to-follow-up between intervention and control group that would 
jeopardize the validity of study findings.  As recommended by the design teams, we will conduct 
semi-annual participant engagement parties (in January and July) that will consist of a meal, 
healthy lifestyle education and games.  We will report enrollment and other study related news to 
participants.  All participants—both intervention and control—will be invited to these events.  
As an additional incentive, control participants will receive a BP monitor and instructions about 
its use after completion of the final 12-month trial visit.   
EXTRA-CVD intervention: Participants randomized to the intervention will meet with the site 
prevention nurse on the day of enrollment. With nurse assistance, the participant will complete 
an initial ASCVD risk assessment using the ACC/AHA risk calculator and a risk visualization 
tool available at https://statindecisionaid.mayoclinic.org/.  This exercise will help establish 
rapport between the participant and the nurse, and will help identify potential targets for 
intervention. The nurse will conduct a baseline medication assessment, including participant’s 
knowledge of the purpose and side effects of each BP or cholesterol medication and current or 
potential adherence strategies.     
Frequency of contact: All subjects will complete the same assessments at the same time-points 
(in-office BPs, lipid profile, perceived ASCVD risk survey, and network analysis survey). The 
prevention nurse will then contact the intervention subjects at up to 2-week intervals as necessary 
to carry out the multi-component intervention. Frequency of contact will be determined 
according to protocol triggers that may be patient or prevention nurse initiated (e.g. home BP 
values are high, checking for side effects after starting a statin). At a minimum, the prevention 
nurse will have face-to-face meetings at 0, 4, 8, and 12 months, as well as a mid-period 
telephone call between in-person visits to “check-in” about home BP values and medication 
adherence. An initial 2-week follow-up call will ensure proper use of the home BP monitor and 
to address any other questions. Two example scenarios of relatively lower intensity and higher 
intensity intervention are shown in Figure 3 with the education control group as a reference. As 
demonstrated by the figure, a strict attention control group is not appropriate since the dose of 
attention will vary according to the needs of the participant.   
 
As with control patients above, study visits must be completed +/- 14 days from the 
calculated visit date.  Visits done between 14 and 28 days after the calculated visit date will be 
considered a protocol deviation.  Visits outside of the +28 day window will not be scheduled and 
that visit will be considered missing for that patient.  The fasting lipid panel blood draw will be 
done at the time of study visit or within a +/- 10 day window.  Study calls will be completed +/- 
14 days of the scheduled due date.  In the event that the study nurse has made no less than three 

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attempts to schedule a participant’s follow-up visit, a letter (Appendix R) will be sent to the 
participant. 
 
EXTRA-CVD Intervention components:  
1. Care coordination. Beginning with initial enrollment, the prevention nurse will coordinate blood 
pressure and cholesterol management for all participants in the intervention arm. Care coordination will 
consist of tailored discussions with the participant and his/her providers about which provider will take 
primary responsibility for BP and cholesterol management. Considerations of patient-provider trust and 
provider comfort level or experience will inform this decision. The prevention nurse will direct 
subsequent management decisions to the designated provider but will facilitate communication by 
notifying the non-designated of any changes to medications. 
At the baseline visit, the prevention nurse will map the participant’s care team and 
communication preferences, to ensure that all providers in the patient’s care team are accounted 
for.  After the initial visit, the nurse will contact members of the participant’s care team through 
normal clinical communication channels which are standard of care for that clinic site (e.g. EMR 
messages, email, phone) to inform them that the participant has been enrolled in the study.  The 
prevention nurse may use this opportunity to discuss any potential modification to suggested 
blood pressure and cholesterol targets.   
In order to better incorporate the prevention nurse into clinic workflow, a number of 
recommendations were made by the design teams.  These include having nurse meet & greet and 
regular staff updates on the study to ensure that communication preferences are respected.    
Component 1—Relevant process evaluation data for aim 3: (1) number and duration of telephone 
calls and emails to providers or providers’ staff; (2) number and nature of communication notes 
Figure 3: Example scenarios of intervention participant contact frequency.  (A) Participant with lower 
intensity requirements; (B) Participant with higher intensity requirement; (C) Control participant.  Squares 
represent in-person visits and lines are telephone contact.  

 
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in EMR; (3) prevention nurse trust & communication ties with providers; (4) time spent 
coordinating care.   
2. Nurse-managed medication protocols and adherence support.  Participants with BP or non-
HDL above goal will receive tailored medication management and adherence support. 
Algorithm-based care to reduce practice variation and clinical inertia has long been 
recommended to assure that patients are not “stuck” at sub-therapeutic doses of medications82.  A 
meta-analysis of nurse and pharmacist-led cholesterol medication adherence interventions 
showed substantial improvements in adherence and 15-20mg/dL reductions in total cholesterol42. 
By using algorithms and clear decision rules to guide medication titration, the prevention nurse 
will make recommendations to providers to improve care by reducing clinical inertia, reducing 
variation, and allowing non-physician staff members to assist in care. A clear and complete 
algorithm will also help simplify the medical regimen and emphasize medications that are 
affordable, effective, and have low side-effect profiles. 
At each visit (in-person or telephone) where recent home BP values (average weekly BP based 
on a minimum of three values) exceed 130/90mmHg (in line with 2017 ACC/AHA hypertension 
guidelines), the prevention nurse will review the medication list with the patient, including any 
recent medication regimen changes and potential side-effects of each medication83. The nurse 
will provide counseling in several areas, including ways to enhance medication adherence and 
prevent or ameliorate side effects.  For example, patients may be given a personalized 
medication schedule that shows when they should take their medications. 
The prevention nurse will use the algorithms described below to decide on appropriate 
recommendations for medication changes and will approach the designated responsible provider 
(HIV, PCP, or non-HIV specialist) for prescriptions and lab orders. The responsible provider will 
ultimately decide on final management decisions and may request to have the participant be 
taken OFF management protocols as clinically indicated (e.g. recent ASCVD events or advanced 
CKD), in which case the participant would continue all other components of the EXTRA-CVD 
intervention. 
Blood pressure. We will use an evidence-based blood pressure treatment algorithm (Figure 4, 
Tables and Figures uploaded separately) adapted from Kaiser Permanente and used in our prior 
studies.84,85 Once-daily medication and combination therapy will be recommended when 
possible. A follow-up a basic chemistry panel will be ordered when adding ACE/ARB, thiazide 
diuretic, or potassium-sparing diuretic. Medication up-titrations will be recommended at 
intervals of 2-4 weeks until control is achieved. Measures not shown in the figure will include 
but will not be limited to: (1) adding agents such as hydralazine, terazosin, clonidine; (2) 
considerations for comorbid kidney disease or prior ASCVD event; (3) avoiding combination use 
of heart rate slowing drugs.

 
 
Figure 4: Blood pressure treatment algorithm 
 
 
 
Other considerations
• Consider medication non-adherence
• Consider interfering agents (e.g. NSAIDS, excess alcohol)
• Consider white coat effect.  
• Consider discontinuing Lisinopril/HCTZ and changing to chlorthalidone 25mg plus Lisinopril 40mg daily. Consider additional agents 
(hydralazine, terazosin, minoxidil)
• Avoid using clonidine, verapamil, or diltiazem together with a beta blocker.  These heart rate-slowing drug combinations may cause 
symptomatic bradycardia over time
• Consider consultation with a hypertension specialist.
Blood Pressure Algorithm
ACE Inhibitor/Thiazide
Lisinopril/HCTZ      
20/25 ½ tab daily
20/25 1 tab daily
20/25  2 tabs daily
Thiazide
HCTZ 25 mg daily
OR
Chlorthalidone 12.5mg Æ 25mg
If ACE intolerant
ARB if ACEI intolerant
Add Losartan 25mg daily Æ 50mg daily Æ 100mg daily
Calcium Channel Blocker
Add Amlodipine 5mg daily [start 2.5mg (½ tab) daily if age >70] Æ 10mg daily
Spironolactone or Beta Blocker
Add Spironolactone 25mg daily Æ 50mg daily * If eGFR >=60 ml/min and K<4.5
Carvedilol 12.5mg bid Æ 25mg bid Æ 50mg bid
If Not Controlled
If Not Controlled
If Not 
Controlled
If Not Controlled

 
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Figure 5A: Cholesterol treatment algorithm (part 1) 
 
 
 
Check Fasting 
Lipid Profile
LDL-C > 250
TG >500
Consult
Specialist
Determine
Non-HDL 
Target
Encourage continued medication 
adherence and healthy lifestyle 
At goal
Not at goal
Already on 
Lipid 
lowering 
agent
Patient discussion and 
diet and lifestyle changes
No
On 
statin
Uptitrate
statin
Consider switching to or adding statin
If no improvement 
after 4 months
Consider high-dose statin (atorvastatin, rosuvastatin)
* If PI/cobicistat interaction, start low (atorva 10 or rosuvastatin 5) 
and titrate up in 6 weeks to max (atorva 20 or rosuva 10)
Not at goal
Not at goal
Consider combination therapy
Not at goal
Not at goal
Risk Category
Criteria
Non-HDL Goal
Low-Moderate
• Most EXTRA-CVD patients
<130 mg/dl
High
• Known ASCVD
• Diabetes + ш2 major risk factors *
<100 mg/dl
Very High
• Multiple Major ASCVD events
• 1 major ASCVD event + risk 
factors* (see below)
<100 mg/dl
Risk Factors for Future ASCVD events
1. Age >65 years
2. Heterozygous Familial Hypercholesterolemia
3. History of prior CABG or PCI outside of the major events
4. Diabetes
5. CKD (eGFR 15-60 mL/min)
6. Current cigarette smoking
7. Congestive Heart Failure
8. Persistently elevated LDL >100mg/dL despite maximally tolerated statin 
therapy and ezetimibe
Cholesterol Algorithm
Major ASCVD events
1. Recent acute coronary syndrome (<12 months)
2. History of MI or stroke (other than recent ACS above)
3. Symptomatic PAD (claudication with ABI <0.85, prior lower-extremity 
revascularization or amputation)

 
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Figure 5B: Cholesterol treatment algorithm (part 2) 
 
 
 
Consider combination therapy
Start ezetimibe 10 mg daily if very high risk and consider starting if 
high risk
If not at goal AND very high risk patient then consider adding PCSK9 inhibitor.  * This may 
require a cardiology consult
1) Alirocumab
- Start at 75mg q 2 weeks; Uptitrate as tolerated to 150 mg q 2 weeks
- 300 mg q 4 weeks
2) Evolocumab
-
140 mg q 2 weeks
-
420 mg q 4 weeks
Consider interim 2-month lipid 
panel to assess non-HDL goal 
Repeat lipid panel in 2 months 
to assess non-HDL goal
If not at goal AND very high risk patient then increase 
dose of PCSK9 inhibitor
OR 
If already at max dose of PCSK9 inhibitor, then 
consider adding bile acid sequestrant:
1) Cholestyramine 4000 – 24000 q day or BID
2) Colesevelam 3750 mg q day or BID
3) Colestipol 5,000 – 30,000 q day to 6 x per day
If at goal, continue current 
therapy
If at goal, continue current 
therapy

 
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Figure 6: Protocol for management of statin associated muscle symptoms 
 
 
 Nurse will evaluate the patient’s symptoms by phone
 Complete PRIMO Questionnaire on RedCap
 Obtain CK, UA and serum creatinine
 Consider additional testing to rule out other causes of myopathy 
(i.e. TSH, ESR, Vitamin D 25-OH)
 Discuss case with primary treating provider 
Patient develops myalgia
Intolerable muscle pain 
with or without CK 
elevation
Rhabdomyolysis
Tolerable muscle pain but 
CK > 5 x ULN
Tolerable muscle pain 
and CK elevation < 5 x 
ULN
Continue statin at same 
or reduced dosage using 
patient preference and 
symptoms as a guide
De-challenge and re-challenge: Discontinue statin 
therapy. Once symptoms resolve, restart the same statin 
therapy at lowest dose or if patient prefers use a 
different statin at lowest dose (if on rosuvastatin switch 
to atorvastatin and vice versa). Gradually increase statin 
dose to goal and as tolerated.
Carefully consider the 
risk – benefit of statin use 
and discuss with patient
If symptoms recur consider:
1) Alternate statin starting at lowest dose and gradually uptitrating as tolerated 
(atorvastatin, rosuvastatin, fluvastatin, pitavastatin, pravastatin) 
2) Rosuvastatin (5 – 10mg) at every other day or weekly dosing
3)   Combination therapy (ezetimibe with lower statin dose)
If symptoms recur stop statin. Once symptoms resolve use non-statin drugs alone 
(Ezetimibe, PCSK9 inhibitors, bile acid sequestrants). See combination therapy 
algorithm for more details
If unable to tolerate non-statin drugs consider red yeast rice

 
 
Cholesterol. We will use an algorithm (Figure 5A-B) adapted from National Lipid 
Association (NLA) guidelines for HIV-infected patients25 and the 2018 ACC/AHA Guideline for 
the Management of Blood Cholesterol81. As a first step, the prevention nurse will determine the 
non-HDL target for each individual participant (Table 1; p. 7).  For most participants in the trial, 
the target non-HDL will be <130mg/dL; however, high risk patients (such as those with history 
of prior ASCVD event) will have a more aggressive goal (<100mg/dL). As recommended by the 
guidelines, our algorithm will address drug-drug interactions with ART, including the safe use of 
higher dose statins (rosuvastatin and atorvastatin) if needed, when drug interactions are present.  
Lipid profiles (total cholesterol, triglycerides, HDL, LDL) will be checked at every in-person 
study visit. The nurse will have access to all cholesterol fractions, but the algorithm will focus on 
non-HDL as the primary target. When a new cholesterol medication is prescribed, the prevention 
nurse will call 2 weeks after initiation to discuss adherence and any possible side-effects. The 
nurse will use an evidence-based approach to evaluation and management of muscle symptoms 
and other intolerances of statins as recommended by NLA guidelines (Figure 6).82,83 This 
approach will include evaluation for other causes, drug-drug interactions, checking creatinine 
kinase levels, trial off statin, retrial of different statin, non-daily dosing of longer acting statin 
(i.e. rosuvastatin), and/or referral to a specialist. 
Component 2—Relevant process evaluation data for aim 3: (1) frequency of BP and 
cholesterol algorithm use; (2) number of telephone contacts and total duration of time required to 
bring an elevated BP or cholesterol level under control; (3) Frequency of statin intolerance and 
proportion of intolerance cases ending in complete cessation of any statin; (4) Number of 
referrals to BP or cholesterol specialists.   
3. Home BP monitoring. Our justification for using home BP monitoring in the EXTRA-CVD 
intervention is that home BP measurements are reproducible with standard deviations of less 
than 3.1 mmHg for both systolic and diastolic measurements84. In addition, home BP monitors 
are accurate and comparable to ambulatory BP monitors85, a ‘gold standard’ of BP 
measurements. Home measurements have greater predictive power for mortality as compared to 
office-based measurements.86 All intervention participants will receive a home BP monitor and 
will be trained according to a developed protocol14 and documentation of proper usage will be 
recorded. Participants will use the BP monitors every day. Prior to each telephone or in-person 
follow-up visit, we will request BP values for the past two weeks using a standardized data 
collection form.  Participants with poor BP control will receive nurse calls every 2 weeks, with 
management changes made as described in component #2 above.  All intervention participants 
will be able to keep the BP monitor after completion of the study.  Control participants will 
receive a BP monitor and instructions about its use after completion of the final 12-month trial 
visit.   
Component 3—Relevant process evaluation data for aim 3: (1) Frequency of home BP 
checks (average checks/week and proportion of weeks with  2 checks); (2) Number and nature 
of medication changes in response to home BP data; (3) Barriers to home BP use; (4) Knowledge 
of proper home BP use. 

 
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4. EMR support tools.  Evidence-based EMR tools that do not result in provider fatigue or 
information overload effectively improve patient outcomes87,88. Our three sites use two of the 
most widely available EMR systems (Epic at MetroHealth/Duke and Allscripts at UH).  At the 
UH Special Immunology Unit, there is also a parallel electronic database that may be used for 
clinical purposes and is amenable to programmable tools.  Beginning in year 1, we will work 
locally with EMR (IT) support to develop these tools to assist the prevention nurse during the 
intervention phase:   
x An extended treatment cascade graphic for the prevention-nurse specialist which will 
appear on his/her “dashboard” or as a recurring pdf report.  During the intervention 
phase, the nurse will have regular access to this graphic and will receive names of 
specific patients who have fallen out of each cascade category. 
x Tool to chart home blood pressures in EMR. 
x Epic SmartSets that pipe in recent lab and BP values and give providers options for 
medication prescriptions based on the treatment algorithms. 
These new tools will only be available to the prevention nurse during the intervention phase, but 
will then be made available to all providers after the intervention is completed. Currently, all 
three sites have automatically calculated 10-year predicated ASCVD risk available to all 
providers for all patients. 
Component 4—Relevant process evaluation data for aim 3: (1) number of times each tool 
is accessed 
Protocol Changes Resulting from Novel Coronavirus Outbreak (COVID-19)  
We will not enroll new participants during the period of spread of the novel coronavirus in the 
United States. No new participants will be enrolled until deemed safe by the affiliated research 
institutions and the HIV clinic directors where the EXTRA-CVD intervention is taking place. 
Study procedures will revert to the original procedures described herein on pages 25-35 once the 
mandates are lifted. During this time, recruitment may continue as described above according to 
the discretion of each study site.  Potentially eligible subjects will be placed on a waiting list to 
be enrolled once mandates are lifted.   
In order to simultaneously reduce transmission of the virus while maintaining the management of 
participant’s cardiovascular care to the best extent possible, pertinent study activities will be 
conducted remotely with currently enrolled participants who are willing and able to access 
HIPAA-compliant virtual platforms (e.g. secure telephone and virtual videoconferencing). These 
relevant research activities include follow-up visits with control and intervention groups and 
periodic check-ins with intervention participants, both described above in the study procedures 
for aim 2. Participants will be compensated for their participation at the same amount specified 
in the original consent through site-specific means such as check or prepaid debit cards by mail 
or direct deposit.  
Participants who cannot or prefer not to participate in remote study activities during this time 
will have 4- or 8- month follow-up visits that are designated as missing. These participants will 
remain enrolled and will be contacted once the COVID-19 public health mandates are lifted and 
will be invited to re-engage in their next calculated visit as described in Figure 3 on page 27.  

 
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All enrolled participants at each site will be notified by mail of these protocol changes enacted 
during the period of public health mandates. 
Once public health mandates for the COVID-19 have been lifted, study sites will re-evaluate the 
safety of conducting in-person visits and will adapt original and new procedures to guidelines of 
their respective institutions, the NHLBI, CDC, WHO, and state and national governments. Study 
procedures for in-person visits will be carried out to capture all original process and outcome 
data elements.  
Follow-Up Visits with Control and Intervention Groups 
Participants currently enrolled at the three study sites may be due for 4- or 8- month follow-up 
visits during the COVID-19 social distancing period.  
For both intervention and control groups, the remote follow-up visits will be focused on 
collecting self-reported survey data, COVID-19-specific questionnaires and symptom screening, 
and engaging in cardiovascular health education with the study nurse. The intervention group 
will also engage in blood pressure and cholesterol care management with the study nurse and be 
asked about medication, blood pressure, cholesterol and clinical care coordination through 
standard tools developed in REDCap.  
The remote visit format will prioritize a subset of self-administered surveys that the study teams 
across the sites have collectively deemed most essential.  Additionally, the procedures have 
expanded to include a set of COVID-19-specific surveys. Refer to the table below for a list of 
these questionnaires. Nurses will inform each participant before the administration of the 
COVID surveys that if they feel uncomfortable completing any of the specific instruments, to let 
the interviewer know and they will skip to the next question or section.   
For those participants with access to the Internet and a computer (including a smartphone), they 
will have the option to receive a REDCap survey link via email to complete before their remote 
visit with the nurse. For those who do not have access to the Internet or who do not complete the 
self-administered surveys before the remote visit, the nurse will attempt to collect the 
information and enter the data into REDCap. All other aforementioned data will be collected by 
the nurse in conversation with the participant and entered into REDCap by the study team.  
Several study team members at each site estimated the time expected to complete the essential 
surveys and care coordination components. From these aggregated responses, we expect the 
remote follow-up visits to take approximately 75 minutes to complete.  
A study protocol BP and blood draw will be attempted in conjunction with any provider-
scheduled clinical encounter deemed essential for clinical care within a +/- 21 day time window. 
If this is not possible, these data will be missing. The window for all study procedures (visits, 
surveys, outcome BP/cholesterol) will be defined as +/- 21 days from the “target visit date”.  The 
target visit date is calculated as 4-, 8-, or 12-months from the baseline visit.   
 
COVID-19 Survey Battery 
Instrument 
Description 
COVID Chaos Instrument 
x This survey will ask participants if they have tested positive, been 
in contact with a positive case and/or had any COVID-19 
symptoms since March 1, 2020.   

 
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x Participants with current symptoms will be referred to the local 
hospital or department of health hotlines. 
x Remaining items cover the following (timeframe: during COVID): 
o Household makeup 
o Activities affecting physical and emotional health 
o Coping strategies  
Loneliness Scale 
A 3-item Likert scale (hardly ever, some of the time, often): 
1. How often do you feel that you lack companionship? 
2. How often do you feel left out? 
3. How often do you feel isolated from others? 
HIV Self-Management Scale, 
Short Form 
A 12-item Likert scale asking the participant to rate how confident 
they are in doing things related to HIV (all, some, none of the time): 
1. Exercising 
2. Physical activity 
3. Spiritual/religious practices 
4. Changing aspects of health  
5. Achieving health goals 
6. Modifying diet 
7. Balancing family priorities with HIV management 
8. Personal time of enjoyment 
9. Job activities helping with health 
10. Educating others on HIV 
11. Positive stress relief 
12. Managing HIV symptoms and medication side effects 
 
COVID-19 Symptom Screening and Referral Procedures 
The COVID symptoms questionnaire asks the participant if they have experienced any COVID-
19-related symptoms (Cough, Shortness of breath, Loss of smell or taste, Runny nose, Sore 
throat, Abdominal pain, Feeling poorly, Chills, Vomiting, Severe headache, Muscle aches) since 
March 1, 2020. If the participant answers yes to any symptom(s), the nurse will inquire about 
symptom duration. Participants with symptoms deemed concerning to the research clinical team 
will be referred by the nurse to the local COVID-19 hotline. The participant will also be 
connected to any other needed services (i.e. mental health counseling through the HIV clinic, 
food deliveries through local food banks, unemployment claims through state governments, 
etc).   
Periodic Check-Ins with Intervention Group 
The interval check-in phone calls with intervention group participants will proceed as described 
in the standard procedures for aim 2, described on page 26-27. The frequency of the intervals are 
driven by protocol triggers already conducted via telephone remotely.  
Semi-Structured Interviews to Assess the Impact of COVID-19 on Cardiovascular Health 
The EXTRA-CVD study will integrate qualitative analysis through semi-structure interviews 
with 36 study participants who have already enrolled into the study as of April 21, 2020. Twelve 
participants at each site (6 intervention and 6 control) will be interviewed.  
Participants will be recruited by the study nurse at each site. The study nurse will ask participants 
during their follow-up visits if they are interested in being interviewed. Those who affirm their 
interest will be contacted by a qualitative researcher at Case Western Reserve University. The 

 
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CWRU qualitative researchers will conduct the interviews for all sites via telephone. The 
interviewer will perform verbal informed consent using an IRB-approved consent script over the 
phone, and the participant will be given ample time to ask questions and, if preferred, review the 
consent script through electronic mail. Participants must verbally give their consent before the 
interview begins. Those who consent will be interviewed during that call, and this process will 
proceed until each site has interviewed 12 participants.  
Names, email address and phone numbers for all study participants who agree to be contacted 
from all 3 sites (UH, Duke and MetroHealth) will be entered by site research staff in REDCap. 
The qualitative researcher at Case will use these contact lists to contact patients and track when 
the interview was performed 
All interviews will be recorded and transcribed, and verbal consent will be captured in a consent 
record as well as in the transcripts. All de-identified data will be stored in a secure location on 
Box and only the qualitative researchers will have access.  
Transcription and coding of the interviews will follow the same analysis procedures as laid out in 
Aim 1. See appendix C, COVID Aim: Key Informant Interview Guide for PLWH to review the 
interview script.  
Participants in this qualitative sub-study will receive $25 compensation for participating, which 
will be distributed to participants in the same manner as other study payments according to local 
site regulations.   
 
Aim 3 Procedures: 
This process evaluation of the EXTRA-CVD trial is based on the framework proposed by 
Saunders et al72.  We will collect information about intervention fidelity, dose delivered, dose 
received (exposure), dose received (satisfaction), reach, and recruitment.   
RedCap instruments will be used to capture the quantitative measures described in each of  4 
component sections above.  Additional redcap instruments will be used to collect scripted 
telephone encounter data, particularly from (a) the initial 2-week check-in and (b) the mid-period 
check-in.  The purpose of scripting the calls is to standardize the intervention as much as 
possible; however, there will be some counseling and other types of follow-up calls (e.g. 
counseling, arranging appointments, etc…) that cannot be completely scripted.   
To additionally monitor intervention fidelity, a study team member who is not the coordinator or 
prevention nurse will observe a study visit with a patient. He/she will rate the Prevention Nurse 
and study staff/coordinator in individual domains using checklists (Appendix L). At least one 
participant encounter will be observed per quarter and the results will be recorded in RedCap; 
however, additional encounters may be observed and recorded in RedCap using the repeated 
measures function. 
For aim 4 process evaluation, a study team member will virtually observe a visit between the 
prevention nurse and patient at each site at least once per quarter using checklists (Appendix Q).  
If the observer is unable to synchronously observe, the prevention nurse will obtain and use a 
script to request and record verbal consent from the participant to record the entire visit either 
using a tape recorder if the visit is conducted by phone or the Zoom recording feature if the visit 
is conducted by Zoom.  If the study team member who obtains informed consent from 

 
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participants for aim 4 is not the prevention nurse, then another study team member (either the 
prevention nurse or another study team member) will similarly observe the person obtaining 
consent.    
Evaluating Study Nurse Motivational Interviewing Skills over Time 
The process evaluation includes measuring the motivational interviewing (MI) skills of study 
nurses at each site over time. Each site has received the same MI training and coaching to learn 
skills that have been proven to build rapport with participants and enhance participant 
motivations to change health-related behaviors.  
We will utilize the Behavior Change Counseling Index (BECCI) (appendix M) instrument to 
measure the practitioner skills involved in motivational interviewing. The BECCI is an 11-item 
instrument that utilizes a Likert scale to measure practitioner behaviors that are core elements of 
fostering participant behavior change talk” in MI. It is a brief instrument that is simple to 
implement even for untrained staff, and has been tested as a valid and reliable measure in 
showing changes in practitioner core MI skills over time. Study coordinators, PI Longenecker, 
and co-investigators at MetroHealth and Duke Health have been trained to complete the BECCI 
through direct observation or upon listening to a recorded segment of a study visit. They have 
also been trained as MI supervisors to provide feedback and coaching to the study nurses based 
on the observation/recording and completion of the BECCI instrument.  
 
For aim 2, starting July 2020, each site’s study nurse will record a ten-minute segment of two 
study visits with a participant during each study quarter. The study nurse will perform verbal 
informed consent using an IRB-approved consent script, and the participant will be given ample 
time to ask questions. Participants must verbally give their consent before the nurse continues the 
recording of the study visit procedures, and this consent will be included on the audio recording. 
Recordings will be captured using a digital recording device that will be kept secure in a locked 
cabinet/desk in a locked room. Recordings will be immediately uploaded to a password protected 
HIPPA-compliant location at the local site (i.e. s: drive at UH site). The study coordinator or 
another trained study member will complete the BECCI after listening to the recording and will 
enter the scores in the REDCap process evaluation arm. No participant PHI will be entered into 
the REDCap BECCI instrument.  A study coordinator will then arrange a time with the study 
nurse to complete the coaching session. During this session, a study coordinator will provide to 
the nurse the BECCI results as well as up to two MI learning resources, and will discuss the 
strengths, areas for improvement, and identify the nurse’s goals for building MI skills over the 
subsequent quarter. These elements will be entered into REDCap under the process evaluation 
arm. To ensure inter-rater reliability, a study coordinator who did not provide feedback will also 
listen to at least one recorded session per site every other quarter and score using the BECCI 
instrument.  Once the BECCI score is completed and feedback is delivered to the study nurse, the 
recording will be deleted from the digital device and any other local storage location. Only the 
study team members will have access to the recording device and audio files. BECCI data will 
also be used in a formative process evaluation at the end of the trial.   
For aim 4, each site’s study nurse will record at least one ten-minute segment of one study visit 
with a participant during each study quarter.  The same informed consent, recording, and storage 
procedures will take place as described above.   
Qualitative Data 

 
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In addition to the quantitative data, we will collect qualitative data for two groups (PLHIV and 
healthcare team members).  Through our experience conducting phone interviews (including 
phone consent) during the COVID-19 pandemic, we have found this approach to be effective and 
desirable from the participant’s perspective.  Therefore, we will take a similar approach for these 
interviews as described below: 
PLHIV and healthcare team member participants will be recruited by the study nurse at each site. 
The study nurse will ask potentially eligible participants if they are interested in being 
interviewed by phone. Those who confrim their interest will be contacted by a qualitative 
researcher who will conduct the interviews for all sites via telephone. The interviewer will 
perform verbal informed consent using an IRB-approved consent script over the phone, and the 
participant will be given ample time to ask questions and, if preferred, review the consent script 
through  email. Participants must verbally give their consent before the interview begins. Those 
who consent will be interviewed during that call, and this process will proceed until each site has 
reached their sample size for each group.  
Names, email address and phone numbers for all study participants who agree to be contacted 
from all 3 sites (UH, Duke and MetroHealth) will be entered by site research staff in REDCap. 
The qualitative researcher will use these contact lists to contact patients and track when the 
interview was performed 
All interviews will be recorded and transcribed, and verbal consent will be captured in a consent 
record as well as in the transcripts. All de-identified data will be stored in a secure location in 
RedCap and only the qualitative researchers will have access.  
Transcription and coding of the interviews will follow the same analysis procedures as laid out in 
Aim 1. See appendix S, Key Informant Interview Guides for PLHIV and Clinicians to review the 
interview script.  
Participants in this qualitative sub-study will receive $25 compensation for participating, which 
will be distributed to participants in the same manner as other study payments according to local 
site regulations.   
 
PLHIV (n=36): At approximately the time of the final 12-month visit, we will approach a 
convenience sample of approximately 8-12 participants per site to participate in an additional 
key informant interview as described below.   
Key Informant Interviews (PLHIV). The virtual interviews will take place following the 12-
month visit at a mutually agreed upon time. Questions will address the participant’s perceptions 
of ASCVD risks associated with HIV, experiences with the EXTRA-CVD intervention and will 
focus on the RE-AIM domains of reach, adoption, and implementation. All interviews will take 
approximately 30 minutes, and audio recordings will later be transcribed verbatim.  
Healthcare team members and site prevention nurses (n=27): We will recruit approximately 
8 healthcare workers per site to provide qualitative feedback on the intervention.  These 
healthcare team member participants will complete a brief self-reported survey consisting of 
demographics, training, and general practice patterns as well as an in-person key informant 
interview. 
We will additionally invite the prevention nurse from each site (n=3) to participate in a 

 
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healthcare team member interview, since they have served as integral members of the healthcare 
team during the patient’s participation in the trial.  We have added additional questions to the 
interview guide (Appendix S) that are specific to the prevention nurses. 
Key Informant Interviews (Healthcare Team members). In a similar fashion as for the PLHIV 
sample, we will conduct individual virtual interviews with healthcare team members to 
understand perceptions of the EXTRA-CVD intervention and will also focus on the RE-AIM 
domains of reach, adoption, and implementation. These ~30minute interviews will be recorded 
and later be transcribed verbatim. The interviewer will also collect basic demographics and 
information about their practice setting. 
Outcomes and analysis: Quantitative data (e.g., demographics) will be summarized and used to 
describe the study samples. After redacting all names and identifying information, verbatim 
transcriptions of recorded interviews will be entered into Dedoose76, a secure, website-based 
analysis program to analyze qualitative data. A quality assurance protocol will be built into data 
management and analysis; 25% of the transcripts will be check to verify accuracy of the 
transcriptions and 10% will be double-coded to ensure inter-coder reliability of 80% or greater. 
Pooled Kappa statistics will be calculated for codes to assess inter-rater agreement.77   
Under PI-Webel’s direction, all responses will be analyzed using standard analytic 
techniques for qualitative data: identification of themes/domains; coding or classification of 
participants’ responses by these themes performed independently by two team members (who 
have graduate-level training in qualitative coding); resolution of any coding discrepancies will be 
done by a third team member.78 To ensure consistency, a codebook and dictionary will be 
developed to create universal definitions for each code. The codebook will contain all codes, 
their definition, and exemplar quotes.  
PLHIV-Provider Trust & Communication Ties 
The success of the EXTRA-CVD intervention to improve blood pressure and cholesterol may 
depend on the nature of the personal relationship between PLHIV participants and his/her 
providers, including the prevention nurse.  Therefore, we have designed our own tool, based on 
validated surveys used in social network analyses, to assess the strength of trust and 
communication ties between PLHIV participants and providers as well as ties between the 
prevention nurse and health care providers/staff.  There will be three sources of data for this part 
of the process evaluation: 
1. Survey completed by the PLHIV participant about each of his/her healthcare team 
members.  This survey will be completed at each in-person visit.  (Appendix I) 
2. Survey completed by the prevention nurse about each PLHIV participant after each in-
person visit.  (Appendix J) 
3. Survey completed by the prevention nurse about providers encountered during the 
course of the trial (completed every 3 months only for those providers with whom the 
prevention nurse interacted during that quarter).  (Appendix K) 
Confidentiality of trust and communication survey responses is especially important.  To that 
end, we have designed these surveys in a way that it is not possible to link responses to 
individual persons as follows: 
1. The surveys will not be conducted in redcap.  Instead, a Case Western Qualtrics platform 
will be used.  The survey links for all sites will be maintained by one study coordinator at 

 
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the UH/Case Western site.  No PHI will be entered into this platform.   
2. The prevention nurse at each site will keep a key of unique identifiers for each provider 
within a patient’s care team network.  The prevention nurse will keep this in a password 
protected file on his/her own personal network drive (to ensure that it is backed-up).  The 
prevention nurse will be the only one with access to this file.   
3. The nurse will prepare the participant who is taking the survey by helping the participant 
enter the unique identifier for his/her HIV provider, HIV-nurse, primary care provider, or 
non-HIV specialist.  The participant will then complete the same set of survey questions 
for each of his/her providers.   
4. On a quarterly basis, or when not fewer than 10 complete records have accumulated, the 
UH/Case Western study coordinator will compile the survey data and link it to exported 
RedCap data using a statistics software program (STATA 13.0).   
5. This completely deidentified dataset will then be sent to two consultants with expertise in 
social network analysis (Dr. Emily Choi, UT Dallas and Dr. Virginie Kidwell-Lopez, U 
North Texas) who will conduct the analyses.   
6. Results will be reported anonymously by site (site A, B, and C), prevention RN (RN1, 
RN2, RN3) and provider (HIV provider 1, PCP 1, etc…).   
Analyses: The primary analysis will be to test the intervention effect on PLHIV-Provider trust 
and communication ties, using a similar repeated measures analysis as described below for the 
primary BP and secondary cholesterol outcomes.  As an exploratory analysis, we will assess 
whether the effect of the EXTRA-CVD intervention on the primary BP and secondary non-HDL 
outcomes are mediated by changes in trust and communication ties.  Additional exploratory 
analyses will be conducted to assess the effect on the balance of trust/communication ties 
between HIV vs. non-HIV providers and to assess the longitudinal change in prevention RN-
provider trust and communication over the course of the intervention.   
Aim 4 Procedures: 
Intervention Adaptation 
The intervention will be adapted with the assistance of stakeholder design teams that have 
already been convened in Cleveland and Durham as part of our original intervention adaptation 
sub-aim 1.1. We now propose an additional round of design iteration to make virtual adaptations 
for this aim. Members of both design teams will be invited to attend combined virtual design 
sessions hosted in Zoom.  
Adaptation Description 
During the Zoom meetings, several suggested virtual enhancements will be presented and we 
will engage in abbreviated exercises to (1) brainstorm, (2) conceptualize, and (3) create new 
virtual enhancements to the intervention. Small working groups will be assigned to further 
develop the enhancements into final products offline, using iterative processes consistent with 
human-centered design principles. The goal of this phase of aim 4 is to present the virtual 
intervention to the design team and move them through a human-centered design process that 
will allow them to adapt intervention elements aimed at improving the overall experience and 
outcomes of participants. Through this process, design team members will: explore the 
intervention in its current conceptual state; consider how the participants living with HIV may 
experience the intervention elements; identify potential challenges PLWH may have in positively 
experiencing the virtual arm of EXTRA-CVD; conceive new ideas and solutions to overcome 

 
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those challenges, and; reach consensus on three key areas of adaptation to improve the aim 4 
intervention for PLWH before enrollment begins.  
Finalized Adaptions  
Three potential virtual enhancements to the EXTRA-CVD intervention were presented to the 
design team for consideration as potential adaptations. These included the following three 
bulleted items.  
 
  
x Virtual Adherence Support Groups: Peer support groups are a long-standing component 
of community HIV care that can address social isolation and improve quality of life for 
PLWH.  We propose asynchronous Facebook groups or synchronous Zoom meetings to 
address social isolation and provide peer-based education to improve CVD self-
management behaviors for PLWH in the US.   
 
x Cardiovascular Prevention Specialist Remote Consultation:  Early qualitative data from 
studies conducted by our study team suggest PLWH want to access high quality CVD 
prevention care but face unique barriers to doing so, including stigma and discrimination 
at visits with specialty providers outside their HIV medical home. One proposed 
EXTRA-CVD adaptation would be to provide all virtual arm participants at least one 
remote consultation from a specialist who would provide recommendations for care and 
consider clinical follow-up as necessary.  
 
x Community Health Worker Technology Coach: Evidence suggests that community health 
workers may be helpful to address psychosocial problems—such as the stress and 
isolation resulting from social distancing—in PLWH. In addition, people who are 
unfamiliar with technology such as smart phones and videoconferencing may be able to 
access them with minimal coaching from technologically savvy family members or 
friends.  We propose considering community based coaches (possibly peers, social 
workers, or case managers) to provide assistance either through home visits or at other 
required points of contact with the HIV clinic. 
 
The design team explored the acceptability and feasibility of implementing these above ideas as 
well as others conceived during the sessions, and opted against prioritizing inclusion of the 
virtual adherence support groups and CVD prevention specialist consultations into aim 4.  
 
Adaption 1: Study Nurse Technology Coach. The design team did reach consensus for the 
inclusion of a technology coach into aim 4, however, recommended that the study nurse at each 
site serve as the coach for participants rather than an added member of the study team. The nurse 
will serve as a technology coach given that they will already be building rapport with the 
participant, and this will allow for the participant to easily identify who to reach out to when they 
need technical support. Each nurse will receive ongoing training and consultation from IT 
experts who are already providing assistance to the study and/or clinical sites. The nurses will 
share their built knowledge with the parent study team during monthly bootcamp learning 
sessions that are already taking place as part of aim 2. The study team has developed an evolving 
virtual technology and engagement toolkit that will serve as a guide for the nurses from which 

 
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they can pull patient-tailored resources and methods to help troubleshoot telehealth issues and 
improve participant engagement.  
 
Adaptation 2: Virtual Communication Preferences Assessment. The design team recommended 
that virtual engagement methods integrated into aim 4 be flexible to meet participant needs and 
include opportunities to build a strong sense of trust and relational connection between the nurse 
and participants. In response to this concern, the study team has developed two tools that the 
design team has approved in helping fulfill the needs of the identified adaptation. One tool will 
be integrated into REDCap and distributed as a survey during their consent visit. This survey, 
called FACETS (Appendix O), is a validated instrument to assess participants’ comfort in and 
access to utilizing various forms of technology. The other tool is a communication preferences 
form (Appendix P) that will be completed as a brief interview with the participant on the day of 
consent. This form will help the nurse gauge which methods of communication the participant 
feels most comfortable using to conduct the study visits, receive study-related education, and 
check in for study-specific follow-ups. The preferences form captures their remote contact 
information, their self-rating for capacity in utilizing various forms of communication 
technology, their sense of privacy and safety in communicating on health issues within their 
home environment, and an open-ended question to understand any concerns they have about 
communicating with the nurse virtually on health issues.  
 
 
Adaptation Components 
The adaptation phase will include one REDCap survey link to collect demographic information 
from all design team participants and an organizational readiness assessment for participants who 
work in the study site HIV clinics. This online survey will take up to 15 minutes to complete. 
This will be followed by three brief, virtual design team sessions, with one being an at-home 
assignment and the remaining two Zoom videoconference meetings. The activities will include: 
1. An assignment called empathy mapping that members will be sent via email and as a link for 
each person to complete at their own pace alone, taking approximately one hour of their time; 2. 
An initial 1.25-hour scheduled Zoom session to discuss the empathy mapping themes and 
generate ideas to enhance the aim 4 intervention, and; 3. A second and final 1.25-hour Zoom 
session to reach consensus on and refine three adaptation ideas. For this virtual design team, a 
focus group discussion on the virtual human-centered design experience will be conducted at the 
end of the final Zoom session among those who consent to participate.  
 
IRB Approval of Adaptations  
Any final adaptations developed by the design team will be shared with the full study team 
during a monthly study call. In order for adaptations to be integrated into the intervention, they 
must be approved by the study PIs. Adaptations that result in changes to the procedures outlined 
in the aim 4 intervention below, or that alter the core components of the intervention, will be 
submitted to the UH IRB as a protocol modification. The team will await IRB review and 
approval of such adaptations before any aim 4 study procedures take place.   
Implementation-Effectiveness Trial 

 
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After deeply assessing the impacts of COVID-19 through interviews conducted with EXTRA-
CVD participants as described above, we will develop a virtual EXTRA-
CVD hypertension intervention that will be well adapted to the post-COVID era. For this hybrid 
3 implementation-effectiveness trial, PLWH participants (n=75) on suppressive ART with high 
BP will be enrolled in the virtually enhanced intervention. Because these subjects are otherwise 
ineligible for or unable to participate in the parent trial, this supplemental study arm will not 
poach potentially eligible participants from the parent trial. EXTRA-CVD study visits and 
components of the intervention will be delivered remotely, and additional remote support tools 
will be tailored to the HIV clinic context with assistance from the Design Team. 
 
The purpose of this additional study is to increase the impact and scalability of the original 
EXTRA-CVD intervention by assessing the social isolation impacts of the COVID pandemic 
and adapting it to post-COVID realities in healthcare delivery. We will accomplish this 
goal without compromising the integrity or feasibility of the parent trial, and will thus increase 
the likelihood of the overall project to exert a sustained and powerful influence on the field.  
 
Frequency of Contact 
For the virtual intervention arm, after in-person written informed consent and a short visit to pick 
up a home BP monitor, all subsequent interactions will be conducted by telephone or 
videoconference, with the exception of home visits from a community health worker technology 
coach. Virtual follow-ups will occur at 2-weeks (Baseline), 4 months, 8 months, and 12 
months.    
Virtual study visits will be calculated from the date of the baseline enrollment visit in months 4, 
8, and 12. Study team members should plan to schedule these visits +/- 14 days from the 
calculated visit date, or 21 days at the most. Visits outside of the maximum 42-day window will 
not be scheduled and that visit will be considered missing for that patient.   
Intervention Components 
The four components of the EXTRA-CVD intervention: (1) nurse-led care coordination, (2) 
nurse-managed medication protocols and adherence support (3) home BP monitoring, and (4) 
electronic medical records (EMR) support tools will be adapted to be delivered 100% virtually 
by telephone or videoconference, with additional supports for social isolation and technology 
coaching developed during the intervention adaptation phase described above.  
The intervention will utilize many of the same procedures as for the parent EXTRA-CVD 
intervention (aim 2). Given that visits will be limited to remote means, however, the study team 
will not collect blood pressure or cholesterol outcome measurements. Study nurses will collect 
participant-reported, at-home BP measures and will provide CVD coaching and care 
coordination through telephone and/or videoconferencing during the 4-, 8-, and 12-month 
follow-up visits. For these follow-ups, the study team will send participants the REDCap survey 
links via e-mail or will administer surveys by telephone.  Our team has experience doing this 
with the EXTRA-CVD study during the early COVID era (March-June 2020), when all study 
procedures were conducted remotely. These surveys include validated instruments assessing 
participants’ experiences with loneliness, HIV self-management, and COVID-specific risks and 
lifestyle impacts. The only EXTRA-CVD surveys which will not be administered to aim 4 trial 
participants are the provider trust and communication surveys, which we believe cannot be 

 
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reliably and confidentially administered by telephone. CVD and HIV-related health information 
will be reviewed by the study nurses before each follow-up visit through the use of each site’s 
electronic medical record (EMR). This study visit preparation using EMR review allows the 
study nurses to coordinate CVD care and medication management with the health team, and 
helps the nurse determine participant progress and elements where participants may benefit from 
CVD coaching during the virtual follow-up visits. Study nurses will coordinate CVD care with 
the participant’s healthcare providers through email and/or EMR support tools, as is being done 
in aim 2.   
Aim 4 Timeline 
Invitations will be sent to the design team members in late October 2020, explaining aim 4 and 
capturing their interest in participating in the adaptation process. The study team expects to begin 
consenting design team members in November and to begin conducting study activities related to 
aim 4 adaptation in November and completing in December 2020.  
The study team plans to begin recruitment and enrollment for the aim 4 intervention in January 
2021 and continue recruitment for six months. In this scenario, the final 12-month follow-up 
study visits for aim 4 are expected to be completed in June 2022, and the process evaluation exit 
interviews to be completed by September 2022.  
 
Nov- Dec 
2020 
Year 1 
Jan – Dec 2021 
Year 2 
Jan – Dec 2022 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Intervention Adaptation: Design 
Team Activities 
 
 
 
 
 
 
 
 
 
Aim 4 Intervention Recruitment & 
Baseline Visits 
 
 
 
 
 
 
 
 
 
4-Month Follow-Up Visits 
 
 
 
 
 
 
 
 
 
8-Month Follow-Up Visits 
 
 
 
 
 
 
 
 
 
12-Month (Final) Follow-Up Visits 
 
 
 
 
 
 
 
 
 
Exit Interviews With Aim 4 
Participants 
 
 
 
 
 
 
 
 
 
 
 
Sources of materials 
Information used to identify potentially eligible patients will be obtained using each site’s 
respective electronic medical record system. We will also use patient reported data obtained after 
consent. We will obtain biometric data (includes lab data, anthropometric and BP measurements) 
from individuals and their electronic medical record system. Trained and certified professional 
staff will obtain all data according to detailed study protocols. Data will be collected directly 
from study participants, medical records, and used specifically for research purposes. 
The following human subjects related data elements will be collected for this study, with the 
source(s) of information noted: 

 
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• 
Subject demographic and clinical characteristics, including age, gender identity, 
race/ethnicity, income, education level, and marital status (self-report), 
• 
Clinical diagnoses, lab values (lipid panels, creatinine, basic chemistries, liver panel, 
HbA1c, creatinine kinase, myoglobin), BP values, and progress notes (electronic medical 
record) 
• 
Communications between care team providers (electronic medical record, telephone logs, 
work emails) 
• 
Prospectively collected lipid panel (total cholesterol, LDL-C, HDL-C, and triglycerides) 
for research (venous blood draw; analyzed in clinical lab) 
• 
Prospectively collected BP for research (rigorous BP measurements by trained research 
assistant according to a validated protocol) 
• 
Subject reported ASCVD risk perceptions and barriers and facilitators to improving 
ASCVD risk (key informant interviews) 
• 
Subject health-related information: perceived ASCVD risk, general health and 
comorbidities (self-report survey and electronic medical records) 
• 
Medication use (self-report and electronic medical record) 
• 
Self-monitoring data: BP values (collected by subject) 
• 
Trust and Communications Ties Survey (self-report) 
• 
Observations of study visits performed by another study team member to ensure fidelity 
Our study team is extremely prudent in keeping subject data secure and confidential. The control 
of access to study databases will be managed centrally by IT systems at each clinic site through 
user passwords linked to appropriate access privileges. This protects forms from unauthorized 
view and modifications as well as inadvertent loss or damage. Database servers at each clinic site 
are secured by a firewall as well as through controlled physical access. We will use a REDCap 
database (projectredcap.org) to store all study data.  REDCap has many security protection 
features that ensure that each person accessing the database has the proper authority to perform 
the functions he or she requests of the data management system. Within the secondary SAS 
databases, UNIX group access control will be used for maintaining similar security. University 
Hospitals REDCap IT will ensure that only IRB-approved individuals on the study team will 
have access to individually identifiable information about human subjects. This will include the 
PIs, co-investigators, project coordinator, statisticians, database/programming team, and research 
assistants. Some of the data above will be accessed from information already collected as part of 
usual care. All additional data from subjects will be specifically collected for the proposed 
research project and not a part of clinical care.  
Potential risks 
Loss of confidentiality. The risks associated with gathering mixed methods data from 
participants by properly trained and supervised research assistants and technical staff is low and 
include risks of loss of privacy and psychological distress.  
Detection of clinically significant problems: Although not caused by study participation, it is 
possible that clinically significant problems will be detected by study staff.  Subjects entering the 

 
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study will have a history of hypertension and hyperlipidemia so we expect to see abnormal 
systolic and diastolic values, as well as abnormal lipid values. All values that reach a safety 
threshold (<90 or >180 systolic BP, <40 or >110 diastolic BP) will be reported to the subjects’ 
care provider. 
Kidney disease and electrolyte imbalances: Some of the blood pressure agents used in the nurse-
managed protocols may cause acute kidney injury and electrolyte imbalances.  Subjects with 
underlying kidney disease at baseline will be at higher risk.   
Other medication side effects: All medications have potential side effects.  Medications used in 
the nurse-managed protocols will be only be recommended by the nurse and must ultimately be 
prescribed by the subject’s treating provider according to his/her best clinical judgement and 
approval.  Common side effects of anti-hypertensive and lipid-lowering medication include but 
are not limited to: bradycardia, lightheadedness and orthostatic hypotension, lower extremity 
edema, kidney injury and electrolyte imbalances (see above), and myalgias.  Rhabdomyolysis, 
glucose intolerance, and hepatic injury are rare complications of statin therapy. 
Physical activity. All subjects will be encouraged to increase their physical activity, raising the 
possibility of musculoskeletal injury or unmasking of ischemic heart disease. Risks from 
increased physical activity will be minimized by encouraging moderate rather than vigorous 
activity. Providers will respond to these patient problems per usual medical practice. 
Smoking. While not a key component of the intervention, all subjects will be encouraged to quit 
smoking (if currently using), raising the possibility of withdrawal symptoms from nicotine 
dependence. 
Psychological risks. We do not anticipate any substantial psychological risks to be associated 
with participation in this study. As part of our assessments, we will ask participants about their 
demographic characteristics (i.e., race/ethnicity, socioeconomic status). It is possible that some 
participants may feel uncomfortable answering some of these questions. We will only ask 
questions that involve data that are important for study outcomes, and we will inform patients 
that they may refuse to answer any interview or survey questions, but still be involved in the 
study. It is also possible that participants may be uncomfortable talking with the Prevention 
Nurse about some topics that are included in patient-based intervention. 
Protections against risk    
The specific risk of participation are noted above; procedures for protection follow.  
Protection of participants’ identities and confidentiality: Because this study involves persons 
with HIV/AIDS, steps must be taken to protect not only the data they provide, but also their 
identities. The following confidentiality-protection steps will be taken: [1] All research staff will 
participate in initial training, follow-up training, and ongoing monitoring and supervision to 
ensure their understanding of ethical issues involved in this research; [2] consent forms will be 
maintained in locked files with limited access, separate from any subject data and will only be 
accessible to the study team; and [3] any personal identifiers linked to data will be removed and 
replaced by code numbers in all records. These steps are not foolproof, and participants will be 
informed of the associated risks at the time of informed consent.  
Research staff will spend approximately 20 hours in initial training sessions and observed 
practice. Training includes reading and discussing research protocols and selected articles about 

 
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interviewing, tracking, participants and attending lecture sessions regarding emergency 
procedures, mandatory reporting, confidentiality, and research ethics. Training also will include 
how to handle transient discomfort or distress related to embarrassing or sensitive discussions as 
well as how to identify and respond to signs of acute distress; experienced supervisors will be 
available for immediate consultation in the event of unexpected acute psychological problems; 
and all staff will be made familiar with referral resources and procedures for psychological, 
social service, substance-use treatment, and other emergency needs. 
Blood Pressure: All participants will have a high risk for CVD, and thus many will be 
prescribed hypertension medications by their health care provider at the outset of the study. It is 
likely that as a result of increased monitoring, we will detect more episodes of abnormal BP 
values. Because of potential high and low BP values, subjects in the intervention arm may have 
their current hypertension regimen adjusted. Safety monitoring of BP will occur in the context of 
home BP monitoring as well as BP measurement during data collection visits. An average SBP at 
any study visit or during home blood pressure monitoring > 180 mm Hg and/or diastolic is >110 
mm Hg will be considered an alert value and will trigger assessment by the clinician. 
Furthermore, an average at any study visit or during a home blood pressure monitoring that is < 
90 systolic or < 40 diastolic would also be considered an alert value and would trigger an 
assessment by a clinician. Participants who have an alert reading at home will be asked to 
contact the clinician directly so that she/he can assess for any cardiovascular symptoms. 
Participants who have an alert BP reading during study visits will be directly assessed for 
cardiovascular symptoms during the visit. Once an alert value has been confirmed the participant 
will be triaged according to follow-up recommendations from Joint National Committee 
Recommendations (JNC 8). Participants will have access to their regular providers as well as the 
following study investigators designated as the clinical contact for each site: Dr. Gripshover 
(infectious disease physician and HIV clinic director; UH Special Immunology Unit), Dr. 
Hileman (infectious disease physician and HIV clinic director; MetroHealth Medical Center) and 
Dr. Okeke (infectious disease physician; Duke Health). If at any time, participants have 
symptoms of acute end organ damage (i.e. current chest pain, dyspnea at rest, new onset of 
blurry vision, or new neurological deficits consistent with a stroke) in the context of an elevated 
BP measurement (SBP >180, and/or DBP >110), participants will be asked to contact the 
clinician and will be advised and assisted in seeking emergency medical care. For participants in 
the intervention group whose average SBP >180 and DBP >110 or SBP < 90 or DBP < 40 but 
are without acute symptoms, the participant’s primary provider will be notified and medications 
will be changed as deemed appropriate by the study team. Follow up contact with the study staff 
will occur within one week. All abnormal blood pressure results will be communicated to the 
clinic director at each site who will be an integral part of triage and ensuring follow up.  Any 
change in medication management or observation of an alert value will be communicated from 
the nurse as soon as possible. The prevention nurse will then generate a note to be entered into 
the electronic medical record and will communicate directly with the subject’s PCP. The 
research nurses will be integrated parts of their respective health clinic. 
Medication adverse effects, including kidney and electrolyte imbalances: All participants who 
are prescribed a clinically indicated new medication according the nurse-managed protocol will 
have that medication prescribed by the participant’s usual health care provider, who will take 
primary responsibility for counseling the patient about side-effects and ordering follow-up 
laboratories.  In addition, each participant will be counseled by the prevention nurse about 

 
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possible side effects and need for any monitoring.  These protocols therefore will provide an 
additional level of monitoring compared to routine clinical care.   
Anti-hypertensive medication: Any patient prescribed an ACE-inhibitor, angiotensin 
receptor blocker, diuretic, or aldosterone antagonist, will be asked to return in 7-10 days 
for a repeat chemistry panel to check kidney function and electrolytes.  The blood 
pressure algorithm will have special recommendations for those with more advanced 
chronic kidney disease (eGFR <60).  Providers caring for study participants with 
conditions including but not limited to CKD and ASCVD, will be permitted to take their 
patients off of any protocolized management.  Providers will take primary responsibility 
for the prescription of any medications in this study.   
Lipid lowering medication: When a new lipid-lowering agent is prescribed, the 
prevention nurse will call 2 weeks after initiation to discuss adherence and any possible 
side-effects. The nurse will use an evidence-based approach to evaluation and 
management of muscle symptoms and other intolerances of statins as recommended by 
NLA guidelines.  This will include ordering of creatinine kinase levels or liver function 
tests when appropriate.   
Unexpected and serious adverse event reporting: A detailed monitoring plan will be included as 
part of the study protocol and submitted to the IRB and reviewed and approved by the funding 
Institute and Center (IC) before the study begins. Prior to initiation of the study, agreement about 
the data safety monitoring plan will be confirmed in order to ensure the safety of subjects and the 
validity and integrity of the data. The prevention nurse or research coordinator at each site will 
report serious adverse events that are unexpected and study related immediately to a study 
physician who will convey this information to the study team, IRB, and NIH. All AE’s and 
SAE’s will be captured, reports will be completed, and entered into the study database. A safety 
report will detail all serious and unexpected adverse events or other unanticipated problems that 
involve risk to study participants or others, and whether these appeared to be related to the study-
based interventions or research assessment protocols. If the study team, UH IRB, or NIH has 
concerns regarding SAEs, the UH IRB will be notified and a copy of the safety summary will be 
filed with the UH and local site IRBs. Actions taken by the UH or local IRB offices in response 
to adverse event concerns will be reported to the NIH. 
Communications between care team providers and the study prevention nurse (electronic 
medical record, telephone logs, work emails) will be collected as a key process measure of the 
intervention.  We will only examine telephone logs to and from study phones used exclusively 
for this research study for the purpose of coordinating care of study participants.  Similarly, we 
will examine emails to and from email addresses created specifically for the study.  Only secure, 
HIPAA compliant hospital email platforms will be used.  The purpose of this is to protect against 
collection of any personal communications that are unrelated to the research study.  
Potential Benefits of the Proposed Research to the Subject and Others 
Potential benefits for subjects may include improved lifestyle, lower blood pressure, and lower 
cholesterol with a consequent reduction in cardiovascular risk. In our previous experience, 
subjects in biobehavioral research studies have generally found participation to be a positive 
experience and they often feel good about helping provide information that has the potential to 
help others like them. Potential benefits to others include the possibility that this research will 
lead to the development of more efficient and effective clinical treatments for patients with 

 
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cardiovascular disease, with the expectation that this would lead to consequent reduction in 
subsequent, cardiovascular complications and death. Given the minimal risks associated with this 
research, and the potential benefit of the proposed findings, the risks to subjects are reasonable, 
especially with our plan to protect subjects from these risks. Subjects will be reimbursed for their 
time spent on study participation. 
Importance of Knowledge to be Gained 
Reducing cardiovascular disease among PLHIV can prevent cardiovascular complications and 
death. This study may establish the effectiveness of a population intervention that can be 
disseminated widely. In particular, this intervention has the potential to be disseminated very 
broadly in HIV-specialty clinic contexts around the United States, because of the potential for 
improved outcomes among many of its beneficiaries. The minimal health risks to participants are 
offset by the potential benefits to them and to society. 
Research Participant Remuneration 
Participant category 
Remuneration 
Aim 1 HCP 
$25 once 
Aim 1 PLHIV 
$25 once 
Sub-aim 1.1 PLHIV 
$25 initial group discussion, $50 for each in-person visit 
($125 total over 6 weeks) 
Sub-aim 1.1 HCP 
$25 once 
Aim 2 Clinical Trial (PLHIV) 
$50 for baseline and 12-month visits, $25 for 4- and 8-
month visits ($150 total) 
Aim 2 COVID sub-study 
$25 once for phone interview 
Aim 3 PLHIV 
$25 once 
Aim 3 HCP 
$25 once 
Aim 4 Design Team  
$50 x 2 Zoom meetings + $50 at home activity = $150 
total 
Aim 4 AAIM High Trial 
(PLHIV) 
$50 for baseline and 12-month visits, $25 for 4- and 8-
month visits ($150 total) 
HCP, healthcare provider; PLHIV, person living with HIV 
Alternatives to Participation 
Participation in the study is voluntary.  If a potential participant chooses not to participate, he/she 
will receive usual care from their HIV specialty care clinic.   
Sharing of Results with Research Participants: 
As an implementation study that aims to improve clinical care of patients, any relevant clinical 
data will be shared with patient participants and/or their clinical care team as they would 
typically be shared through the course of clinical care.  This primarily consists of home blood 
pressure data (intervention arm) and lipid panels, which will result in the electronic health record 
for both intervention and control participants.  Because of the need to maintain the integrity of 

 
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the control condition, the prevention nurse will not directly communicate blood pressure or 
cholesterol results to the control group participants or their providers unless they exceed the 
safety thresholds defined above.  Results of surveys acquired for research purposes only will not 
be shared directly with participants.  At the end of the trial, final aggregate primary results will 
be disseminated to participants through presentations to local community advisory boards and/or 
clinic staff at the local sites.   
 
Data Safety Monitoring: 
All elements of the data and safety monitoring plan will be reviewed by the IRB at UH 
and provided to the NIH institute overseeing the project. The study PIs—Dr. Longenecker, Dr. 
Webel, and Dr. Bosworth together with the UH IRB PI Dr. Gripshover—will share responsibility 
for monitoring risks to human subjects and implementation of the monitoring plan. The project 
will utilize existing medical referral sources and physicians knowledgeable about HIV to address 
any physical risks that might arise. Serious adverse events will be reported promptly to the 
institution’s IRB and project officer of the funding source. Monitoring procedures and reporting 
and action plans for data and safety-related risks are described below. The Data and Safety 
Monitoring Plan includes the following components which will be addressed individually below: 
• 
Regulatory Issues 
• 
Data Safety and Monitoring Board 
• 
Data Validity/Integrity  
• 
Protocol Compliance 
• 
Termination for Significant Risk 
Each of these components have multiple procedures to safeguard the wellbeing of study 
subjects and to maintain the scientific integrity of the project while achieving the study’s specific 
aims. Key components of the data and safety monitoring plan include weekly meetings of core 
members of the research team (at minimum, the Principal Investigators, Project Director and 
Research Assistants) and monthly meetings of the extended research team including Dr. 
Longenecker, Dr. Gripshover, Dr. Webel, Dr. Bosworth, Dr. Okeke, Dr. Bloomfield, Dr. Smith, 
Dr. Vedanthan, site prevention nurses and research coordinators.  
Meetings of Core Members of the Research Team:   
The PIs will run monthly conference calls with the entire study team which will include 
core protocol team along with study coordinators, prevention nurses, and other representatives 
from each of the 3 study sites. The agenda for these meetings will include tracking of subject 
recruitment, enrollment, and retention; data collection and entry; and documentation and review 
of any subject concerns or adverse effects. These meetings will help ensure that the project 
timeline is being met.   
Regulatory Issues 
Adverse Events Protocols:   
An adverse event is defined as any reaction, side effect, diagnosis or untoward event that 
either a) occurs during the course of the clinical trial and was not present at baseline; or b) was 

 
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present at baseline and appears to worsen during the study. All AE’s will be reported to one of 
the study PIs. All subjects will be aware of their rights prior to participation and will be 
encouraged to report any incidents or adverse effects to the investigators and the Case Western 
Reserve University Institutional Review Board (IRB). Contact information for the investigators 
and the IRB will be provided in all the consent materials. During assessments the research staff 
will inquire about AEs and complete an AE form for each subject. In the event that the 
participant is experiencing a worsening of symptoms, the Research Assistant will, with 
participant’s permission, inform the clinic director. The study PIs, and research staff will 
together determine if the AE places the participant at risk if study treatment is continued.  
All adverse events, with the exception of clinically insignificant events and minor 
common illnesses and injuries (e.g., cold/flu, scrapes, upset stomach, low-grade headaches) will 
be documented on an AE Log. Should any study subjects express concerns about the study 
and/or their participation in the study or express distress as a result of their participation, the 
witnessing research team member will document this in the AE Log. AEs will be reported to the 
study PIs and the study research staff to determine whether and what actions might be 
appropriate. Any AEs determined to be serious and/or study-related will require the completion 
of an AE form to be entered into the project database.  
During research staff training, procedures for AE identification, collection and reporting 
will be reviewed in detail. Study staff will be trained to provide crisis intervention and referral as 
is standard operating procedure within each clinic for such situations, should they become 
dangerous or life-threatening (i.e. suicidal ideation or attempts).   
AEs will be managed in conjunction with clinic medical staff, with permission from the 
participant. All subjects will be ongoing patients at a study site clinic and thus subjects can be 
monitored and have access to medical staff throughout the study period.  
Data and Safety Monitoring Board 
According to guidelines established by the NIH for clinical trials, the investigators will 
establish a Data and Safety Monitoring board (DSMB) composed of independent research 
scientists not otherwise connected with the study. This committee (which is independent of the 
study investigators) will be set up to monitor the study results for evidence of adverse or 
beneficial treatment effects throughout the study period. The Monitoring Committee will remain 
“blinded” to outcome characteristics of the study for as long as possible. While the committee 
may have access to information that is deemed necessary to make an appropriate determination, 
highly sensitive information in relation to the outcome of the study will be requested on a “need 
to know” basis as it may arise during the course of the committee’s deliberations. The 
committee’s concerns will be directed to patient accrual rates, appropriate follow-up, 
compliance, data acquisition, undue complications, and whether the study as it is currently being 
conducted will be able to answer the proposed hypotheses. Additional responsibilities will 
include monitoring the integrity of data collection, reviewing training and compliance with all 
components of the interventions and monitoring for adverse events. The membership and 
frequency of meeting are at the discretion of the funding institute but will consist of 3-5 members 
with appropriate expertise, for example in biostatistics, cardiovascular disease, behavioral 
interventions, HIV research, and clinical trials. It is expected that this committee will meet once 
per year in person and once via conference call and will report to the funding institute on 
scientific and administrative issues. We do not anticipate any real harm to patients, but adverse 

 
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events will be monitored. Adverse event forms will be used to report all unanticipated events. 
The following information will be included in the report: date of event, attribution to 
intervention, and outcome of adverse events. Death will be reported within 24 hours. 
Unanticipated adverse events will be reported within 7 days. Reports will be submitted 
electronically to the CWRU IRB and NIH. A written follow-up will be submitted within 30 
calendar days. All adverse events (serious or not, related or unrelated, anticipated or 
unanticipated) will be reported in the annual report to the CWRU IRB and NIH. 
The DSMB members and contact information is shown in the following table (members 
appointed Jan 2019): 
MEMBER NAME 
EMAIL 
EXPERTISE 
Ann Avery, MD * 
MetroHealth (Cleveland, OH) 
aavery@metrohealth.org 
HIV Medicine 
Matthew Feinstein, MD 
Northwestern (Chicago, IL) 
matthewjfeinstein@northwestern.edu Cardiology 
J. Craig Phillips, LLM, PhD, 
RN, APRN, ACRN, FAAN 
Univ of Ottawa (Ottawa, 
Canada) 
Craig.Phillips@uottawa.ca 
Nursing and Human 
Rights Law 
Steven Grambow, PhD 
Duke University (Durham, 
NC) 
steven.grambow@duke.edu 
Epidemiology and 
Statistics 
* Chair 
 
Termination for Significant Risk 
Diligent monitoring will occur as specified above under Adverse Events Protocols. A 
participant that expresses concern about his or her participation or reports distress associated 
with the research procedures may be asked to discontinue participation in the study if there is 
concern about participant safety and wellbeing or about the safety and wellbeing of others. 
Likewise, if one of the research assistants or supervising members of the Research Team 
expresses a concern about a participant’s safety or wellbeing, the Adverse Events Protocol would 
be used and it is possible that the participant could be asked to discontinue participation if there 
were concern about his or her, or others’, safety and wellbeing. 
 
Data Validity/Integrity:  
Recruitment:  
Participant recruitment will be tracked and reviewed in the weekly meetings of the 
research team. In order to maintain confidentiality, the list, which includes the names of all 
potential subjects, will be kept separately from the documentation and tracking spreadsheet in a 
secure folder. Basic demographic information, as well as reasons for refusal, will be noted for 
eligible individuals who decline participation. Tracking will be carried out to determine which 

 
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and how many individuals are interested in study participation, are eligible for study 
participation, enroll in the study, and complete the first assessments.  
Enrolled subjects will be given code numbers and their study participation will continue 
to be tracked via spreadsheet, which will include documenting the occurrence and date of 
completion of data collection.  
Consistency of Data Collection:   
Data collection will follow study procedures. Data collection will be tracked as specified 
above and will be monitored in the weekly meetings of key members of the research team. Any 
issues that arise can therefore be dealt with in a timely manner. Weekly meetings will also 
include review of upcoming data collection so questionnaires can be prepared in a timely 
manner.  
Quality Assurance: 
Drs. Longenecker, Webel and Bosworth will work closely with the statistician (Dr. 
Smith) to design forms and a database that maximize accurate data entry. Common data elements 
will use the standardized codes and attempts will be made to harmonize all database codes with 
NIH initiatives. To minimize data-entry error and data-management miscoding, questionnaire 
data will be collected via tablet computers and immediately uploaded to a secure web-based 
server, ensuring backup. The electronic files from all sites will be merged into one REDCap data 
management file. Summary results will be entered into the larger REDCap database. Source 
documents and electronic data will be checked for accuracy and adherence to study protocols. 
Data Storage: 
Consent forms and subject lists will be stored in locked file cabinets separate from subject data 
and on password-protected computers, and will be only accessible to the research team. All 
subject data will be labeled only with a code number. These coded data will be kept separate 
from the master list that links subjects and their code numbers. All subject data will be kept in 
locked file cabinets in a locked office. Coded data stored on the computer will be maintained in 
password-restricted files. Any breach in confidentiality will be reported to the PIs. 
 
Statistical Considerations  
The primary outcome will be systolic BP at 12 months and secondary outcome will be 
non-HDL cholesterol at 12 months, both measured at 4 time-points (0, 4, 8, and 12 months). All 
BPs used for outcomes will be obtained by a blinded research assistant and cholesterol levels 
will be measured by lab personnel who are also blinded to treatment group. Because the 
outcomes are continuous, linear mixed-effects models89 (LMM) will be used to examine the 
differences over time between the study arms. LMM will allow us to implicitly account for the 
correlation between a patient's repeated measurements over time. The general mean structure of 
the LMM we will use to examine the hypotheses is, ܻ௜௝ൌߚ଴൅ߚଵכ ܫሺ݉݋݊ݐ݄ൌͶሻ൅ߚଶכ
ܫሺ݉݋݊ݐ݄ൌͺሻ൅ߚଷכ ܫሺ݉݋݊ݐ݄ൌͳʹሻ൅ߚହכ ܽݎ݉כ ܫሺ݉݋݊ݐ݄ൌͶሻ൅ߚ଺כ ܽݎ݉כ
ܫሺ݉݋݊ݐ݄ൌͺሻ൅ߚ଻כ ܽݎ݉כ ܫሺ݉݋݊ݐ݄ͳʹሻǡwhere ܻ௜௝ represents the outcome of interest (i.e., 
SBP or non-HDL) for patient i at time j. In this model, we fit a common intercept and arm is the 
intervention group indicator. Similarly, time is classified, where for example, ܫሺ݉݋݊ݐ݄ൌͳʹሻ is 
a dummy variable equal to 1 for the 12 month time point. Random intercepts will be included for 

 
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each individual to account for correlation among repeated measurements over time. The primary 
analytic model will adjust for clinic site. The mixed effects model parameters will be estimated 
and tested using SAS PROC MIXED (SAS Institute, Cary, NC), and the hypothesis of between-
arm differences over time will be tested using estimate statements within PROC MIXED. In 
particular, ߚ଻, the estimated difference in outcome between arms at 12 months, will be the 
primary effectiveness outcome assessed.  
For the tertiary outcome of cascade category, we will calculate an ordinal four-level 
variable at baseline, 4, 8, and 12 months. We will use a proportional odds model fit via 
generalized estimating equations to examine differences over time between study arms. The 
proportional odds assumption will be assessed using score tests, and the model will be relaxed to 
partial proportional odds if necessary. Robust sandwich standard errors will be used to account 
for potential overdispersion and correlation among the repeated observations over time. Similarly 
to the primary analysis, the model will adjust for clinic site and include the same general mean 
model specification. The primary hypothesis will be tested via SAS PROC GENMOD to assess 
whether the estimated proportions in each level at 12 months differ between arms. All analyses 
will be conducted following an intention to treat (ITT) principle. 
Missing Data:  
We will assess mechanisms for missing data in this study. LMM, implicitly 
accommodates missingness when the response is Missing At Random (MAR); that is, when 
missingness is due either to treatment, to prior outcome, or to other baseline covariates included 
in the LMM. We will address missing data by imputing missing values using multiple imputation 
procedures as described by Schafer. Once missing values have been imputed, each multiply-
imputed data set can be analyzed using the LMM. Final parameter estimates and their standard 
errors will be calculated using Rubin’s formula. We will analyze our data and report final study 
results with and without employing the multiple imputation strategy (compared to complete case 
analysis) and carefully examine and describe any discrepancies found. 
Power:  
The power calculation for this study was based on our prior nurse-led BP intervention12, a 
meta-analysis of cholesterol medication adherence interventions42, and baseline blood pressure 
and cholesterol data from our clinic sites. Power estimates were derived empirically via 
simulation in SAS 9.4. Simulated data were generated based on estimates from prior studies, 
such that we assumed a mean SBP at baseline of 145mmHg for both arms, with a reduction in 
the education control arm of 1mmHg by 12 months For the intervention arm, we evaluated effect 
sizes (differences from education control at 12 months) of 5-7mmHg. We estimate that 15% of 
patients may drop out by the 12-month time point, and incorporated missing values into the 
simulated data based on a uniform pattern of 5% missing at 4 months, 10% at 8 months, and 15% 
at 12 months. The drop-out rate is consistent with prior interventional studies at our sites (80-
88% retention at 12 months).11,12,90 We conservatively estimated variance components assuming 
a total standard deviation of 17 and a within-individual correlation of 0.4 among repeated SBP 
measurements. Similarly, for the secondary non-HDL outcome, we assumed a baseline value of 
132mg/dL with a standard deviation of 41 and a within-individual correlation of 0.7, and 
evaluated sample size needed over effect sizes ranging from 10-20mg/dL. 
After generating 1,000 simulated datasets under these assumptions, we fit the LMMs 
described above to each and assessed the effect of interest using two-sided tests with a type I 

 
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error rate of 0.05.  Based on results, we will have >80% power to detect a 6mmhg lower systolic 
BP and >90% power to detect a 15mg/dL lower non-HDL cholesterol in the intervention arm vs. 
education control. Table 5 displays the sample sizes needed to detect a range of plausible 
clinically significant BP and non-HDL effects. A 6 mmHg improvement in systolic BP is 
associated with a ~20% decrease in ASCVD events91, and a 15mg/dL improvement in 
cholesterol is associated with ~10% decrease in clinical ASCVD events31. 
Table 5: Sample size estimates to detect a range of plausible and clinically significant effect 
sizes 
 
BP Effect Size 
Non-HDL Effect Size 
5mmHg 
6mmHg 
7mmHg 
10mg/dL 
15mg/dL 
20mg/dL 
70% Power 
278 
190 
140 
248 
110 
64 
80% Power 
350 
234 
178 
310 
148 
80 
90% Power 
466 
340 
232 
424 
184 
104 
Green cells represent sample sizes that are less than our proposed sample size (n=300). 
Pre-specified sub-group analyses of the primary, secondary, and tertiary outcomes will 
include clinic site, sex, and baseline ASCVD risk (<20% 10-year risk92 vs. >20% or prior 
ASCVD).  For each category, we will examine the interactions with intervention arm and time. 
Generally, the modeling approach will mirror that described above for each outcome. Three 
separate analyses for each outcome will be conducted to assess the effect of each potential 
moderator. Models will be fit in SAS PROC MIXED and GENMOD, as described above, and 
the moderating effect of each of the three factors will be assessed via the hypothesis test of the 
three-way interaction among subgroup, treatment, and time at 12 months. 
 
ClinicalTrials.gov requirements 
This application includes a trial that requires registration in ClinicalTrials.gov. The registration 
number for this trial is NCT03643705. 
 
Multiple Principal Investigator Leadership Plan 
This project will have three NIH co-Principal Investigators (co-PI) and a fourth University 
Hospitals Principal Investigator to oversee the IRB:   
1. Dr. Chris Longenecker, MD (NIH contact PI)—Associate Professor of Medicine; 
University of Washington School of Medicine; Seattle, WA 
2. Dr. Hayden Bosworth, PhD (NIH MPI)—Research Professor of Population Health, 
Medicine, Psychiatry, and Nursing; Department of Population Health Sciences; Duke 
University School of Medicine; Durham, NC 
3. Dr. Allison Webel, RN PhD (NIH MPI)— Professor of Nursing; University of 
Washington School of Nursing; Seattle, WA 
4. Dr. Barb Gripshover, MD (UH IRB PI)—Professor of Medicine; University Hospitals 
Cleveland Medical Center and Case Western Reserve University School of Medicine; 
Cleveland, OH 

 
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Rationale: We have chosen the multiple PI approach because developing innovative strategies to 
address the increasing burden of cardiovascular risk among people living with HIV (PLHIV) 
requires collaborative, interdisciplinary research.  Furthermore, the two junior co-PI’s 
(Longenecker and Webel) who are emerging as independent scientists in their field, will benefit 
from the experience of a senior implementation scientist (Bosworth) with a proven track record 
developing successful and scalable non-physician-led interventions to address cardiovascular 
risk factors in the VA and general US population.   
Roles and Responsibility: Dr. Longenecker will be the contact PI and will be responsible for 
communication between the PIs and the NIH.  Dr. Gripshover will serve as the site PI for UH 
and take responsibility for logistical study operations at the University Hospitals site and will 
serve as the primary clinical contact person for that site (similar to the role that co-I’s Dr. 
Hileman (MetroHealth) and Dr. Okeke (Duke) will perform at their respective sites).  After 
11/1/2021, Dr. Gripshover will also assume other regulatory, training, or enrollment 
responsibilities at the UH site.  Dr. Bosworth will take primary responsibility for overseeing the 
conduct of the clinical trial (aim 2) and will supervise logistical operations for all 3 aims at the 
Duke site in conjunction with Dr. Okeke. Dr. Bosworth will supervise data collection for aim 2 
and has a long track record of collaboration with the project statistician (Dr. Smith) as well as 
with Dr. Okeke. Dr. Webel will take primary responsibility for supervising the qualitative 
research conducted for the baseline assessment (aim 1) and for the process evaluation (aim 3).  
The budget allocations have been assigned according to these roles and the effort required to 
fulfill them (see budget justification).  The study PIs will share responsibility for monitoring 
risks to human subjects. Publication oversight will be based on the relative contributions of all 
team members, with final decisions regarding first and senior authorship to be made jointly and 
with consensus by the 3 co-PIs.  In the unlikely event of a disagreement, the core protocol team 
will vote to resolve the disagreement as described below.   
Governance: The leadership responsibilities for the study team will be shared by the three co-
PIs as described above.  Additional members of the core protocol team include the following co-
investigators: Dr. Corri Hileman (ID/HIV specialist and MetroHealth HIV clinic director; R01-
funded physician scientist studying CVD co-morbidity in HIV; 8 years of multiple collaboration 
with PI Longenecker), Dr. Lance Okeke (ID/HIV specialist at Duke; studies CVD co-morbidity 
in HIV and mentored by PI Bosworth), Dr. Gerald Bloomfield (Duke cardiologist; expert on 
CVD in HIV, multiple collaborations with PI Longenecker), Dr. Rajesh Vedanthan (NYU 
cardiologist; NHLBI R01-funded implementation scientist; prior collaborations with Dr. 
Bloomfield and Dr. Longenecker).  Given PI Longenecker’s transition to UW, site PI Gripshover 
will assume on-site responsibilities at UH. If any additional PIs move to a new institution, 
attempts will be made to transfer the relevant portion of the grant to the new institution. In the 
event that a PI cannot carry out his/her duties, a new PI with appropriate expertise and skills will 
be recruited as a replacement at one of the participating institutions. 
Communication: The co-PIs will run monthly conference calls with the entire study team which 
will include core protocol team along with study coordinators, prevention nurses, and other 
representatives from each of the 3 study sites.  Dr. Longenecker and Webel have offices within 
<5min walking distance of each other on the UW campus.  The entire study team will meet at a 
critical juncture at the end of Year 1 for a team meeting in Cleveland in order to promote healthy 
team dynamics and to conduct some of the study aims as described in the research strategy 
(initial presentations to the sub-aim 1.2 design team, training for aim 2, etc…).   

 
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Decision Making and Conflict Resolution: Decision-making about study conduct and scientific 
direction will be made by the core protocol team.  We anticipate that any minor conflicts that 
arise will be resolved through direct communication, and we plan to use that as our main 
approach. The team will mediate any conflicts between study PIs, in the unlikely event that the 
conflict cannot be resolved with direct communication. For issues that only affect this proposal 
and where voting is appropriate, a simple majority of the core team will rule. The DSMB also is 
available for mediation if an issue arises regarding subject safety.   
 
 
 

 
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13. Timeline: 
Timeline 
Year 1 
Year 2 
Year 3 
Year 4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Administrative 
  Develop protocols 
and study forms 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Train staff 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Team meeting in 
Cleveland 
 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1 
  Mixed-methods data 
collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sub-aim 1.1: 
  Development 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Acceptability & 
Feasibility Testing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 2 
  Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Follow-up 
assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 3 
  Process evaluation 
data collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Perceived risk and 
network surveys 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Qualitative studies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 4 
Virtual intervention 
adaptation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implementation – 
effectiveness trial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Products 
  Scientific meetings 
& publications 
 
 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
 
 
 

 
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Appendix A: Health Beliefs for Cardiovascular Disease Survey 
 
Strongly 
Disagree 
 
 
Strongly 
Agree 
1.It is likely that I will suffer from a heart attack or stroke in the 
future 
1 
2 
3 
4 
2. My chances of suffering from a heart attack or stroke in the 
next few years are great 
1 
2 
3 
4 
3. I feel I will have a heart attack or stroke sometime during my 
life  
1 
2 
3 
4 
4. Having a heart attack or stroke is currently a possibility for me  
1 
2 
3 
4 
5. I am concerned about the likelihood of having a heart attack or 
stroke in the near future 
1 
2 
3 
4 
6. having a heart attack or stroke is always fatal 
1 
2 
3 
4 
7. Having a heart attack or stroke will threaten my relationship 
with my significant other 
1 
2 
3 
4 
8. My whole life would change if I had a heart attack or stroke  
1 
2 
3 
4 
9. Having a heart attack or stroke would have a very bad effect on 
my sex life 
1 
2 
3 
4 
10. If I have a heart attack or stroke I will die within 10 years  
1 
2 
3 
4 
11. Increasing my exercise will decrease my chances of having a 
heart attack or stroke 
1 
2 
3 
4 
12. Eating a healthy diet will decrease my chance of having a 
heart attack or stroke 
1 
2 
3 
4 
13. Eating a healthy diet and exercising for 30 minutes most days 
will help to prevent a heart attack or stroke 
1 
2 
3 
4 
14. When I exercise I am doing something good for myself 
1 
2 
3 
4 
15. When I eat healthy I am doing something good for myself 
1 
2 
3 
4 
16. Eating a healthy diet will decrease my chances of dying from 
cardiovascular disease 
1 
2 
3 
4 
17. I don’t know appropriate exercises to perform to reduce my 
risk of developing cardiovascular disease 
1 
2 
3 
4 
18. It is painful for me to walk for more than 5 minutes walking 
1 
2 
3 
4 
19. I have access to exercise facilities and or equipment  
1 
2 
3 
4 
20. I have someone who will exercise with me  
1 
2 
3 
4 

 
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21. I don’t have time to exercise for 30 minutes a day on most 
days of the week 
1 
2 
3 
4 
22. I don’t know what is considered a healthy diet that would 
prevent me from developing cardiovascular disease 
1 
2 
3 
4 
23. I don’t have time to cook meals for myself 
1 
2 
3 
4 
24. I cannot afford to buy healthy foods 
1 
2 
3 
4 
25. I have other problems more important than worrying about 
diet and exercise 
1 
2 
3 
4 
 
 
 
 

 
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Appendix B: Adherence to Hypertension and Cholesterol 
Medication Scales  
Adherence for blood pressure medication 
In order for blood pressure medication to work, people have to take it according to their doctor’s 
instructions. For one reason or another, people can’t or don’t always take all of their pills as 
prescribed. We want to know how often you have missed your blood pressure medication. Please 
rate your agreement with the following statements.  
Over the past 7 days… 
 
 
 
 
1. I took my blood pressure 
medication as prescribed.  
Strongly disagree                           Strongly agree 
 
2. I missed or skipped at least one 
dose of my blood pressure 
medication. 
Strongly disagree                           Strongly agree 
 
3. I was not able to take all of my 
blood pressure medication. 
Strongly disagree                           Strongly agree 
 
Scoring instructions: nonadherence scale score - calculating the mean of the three extents of 
nonadherence items. Higher scores indicate greater levels of non-adherence 
 

 
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Reasons for Nonadherence to Blood Pressure Medicines 
Situations come up that make it difficult for people to take their blood pressure medications as 
prescribed by their doctors. Below is a list of those situations. We want to know how much these 
situations contributed to you missing a dose of your medication. Only one of these situations 
may apply to you, or many may apply to you. 
In the past 7 days, how much did each situation contribute to you missing a dose of your blood 
pressure medication? 
1. I was busy 
 
       Not at all                                  Very much 
 
2. There was no one to remind me 
 
       Not at all                                  Very much 
 
3. They caused some side effects  
 
       Not at all                                  Very much 
 
4. I worried about taking them for the rest 
of my life 
       Not at all                                  Very much 
 
5. They cost a lot of money  
 
       Not at all                                  Very much 
 
6. I came home late  
 
       Not at all                                  Very much 
 
7. I did not have any symptoms of high 
blood pressure 
       Not at all                                  Very much 
 
8. I was with friends or family members 
 
       Not at all                                  Very much 
 
9. I was in a public place 
 
       Not at all                                  Very much 
 

 
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Scoring instructions: These items are used individually; no total score is computed.  
10. I was afraid of becoming dependent on 
them 
       Not at all                                  Very much 
 
11.  I was afraid they may affect my 
sexual performance 
       Not at all                                  Very much 
 
12.  The time to take them was between 
my meals 
       Not at all                                  Very much 
 
13. I felt I did not need them 
 
       Not at all                                  Very much 
 
14. I was travelling 
 
       Not at all                                  Very much 
 
15.  I was supposed to take them more 
than once a day 
       Not at all                                  Very much 
 
16. I had other medications to take 
 
       Not at all                                  Very much 
 
17.  They make me want to urinate while 
away from home  
       Not at all                                  Very much 
 
18.   I ran out of medication  
 
       Not at all                                  Very much 
 
19.  I was afraid the medication would 
interact with other medication I take  
 
       Not at all                                  Very much 
 
20.  My blood pressure was too low  
 
       Not at all                                  Very much 
 
21.  I was feeling too ill to take them 
       Not at all                                  Very much 
 

 
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Adherence for cholesterol lowering medication 
In order for cholesterol medication to work, people have to take it according to their doctor’s 
instructions. For one reason or another, people can’t or don’t always take all of their pills as 
prescribed. We want to know how often you have missed your cholesterol medication. Please 
rate your agreement with the following statements.  
Over the past 7 days… 
 
 
 
 
4. I took my cholesterol medications 
as prescribed.  
Strongly disagree                           Strongly agree 
 
5. I missed or skipped at least one 
dose of my cholesterol medications. 
Strongly disagree                           Strongly agree 
 
6. I was not able to take all of my 
cholesterol medication. 
Strongly disagree                           Strongly agree 
 
Scoring instructions: nonadherence scale score - calculating the mean of the three extents of 
nonadherence items. Higher scores indicate greater levels of non-adherence 
 

 
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Reasons for Nonadherence to Cholesterol Medicines 
Situations come up that make it difficult for people to take their cholesterol lowering medication 
as prescribed by their doctors. Below is a list of those situations. We want to know how much 
these situations contributed to you missing a dose of your medication. Only one of these 
situations may apply to you, or many may apply to you. 
In the past 7 days, how much did each situation contribute to you missing a dose of your 
cholesterol medication? 
1. I was busy 
 
       Not at all                                  Very much 
 
2.  I forgot 
 
       Not at all                                  Very much 
 
3.  The medication caused some side 
effects. 
       Not at all                                  Very much 
 
4. I worried about taking them for the rest 
of my life 
       Not at all                                  Very much 
 
5. They cost a lot of money  
 
       Not at all                                  Very much 
 
6. I came home late  
 
       Not at all                                  Very much 
 
7. I did not have any symptoms of high 
cholesterol 
       Not at all                                  Very much 
 
8. I was with friends or family members 
 
       Not at all                                  Very much 
 
9. I was in a public place 
 
       Not at all                                  Very much 
 

 
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Scoring instructions: These items are used individually; no total score is computed.  
10. I was afraid of becoming dependent on 
them 
       Not at all                                  Very much 
 
11.   I was afraid they may affect my liver.        Not at all                                  Very much 
 
12.  The time to take them was between 
my meals 
       Not at all                                  Very much 
 
13. I felt I did not need them 
 
       Not at all                                  Very much 
 
14. I was travelling 
 
       Not at all                                  Very much 
 
15.   I was supposed to take them too 
many times a day. 
       Not at all                                  Very much 
 
16. I had other medications to take 
 
       Not at all                                  Very much 
 
17.   I was afraid they would cause muscle 
pain. 
 
       Not at all                                  Very much 
 
18.    I ran out of medication 
       Not at all                                  Very much 
 
19.  I was afraid the medication would 
interact with other medication I take 
 
       Not at all                                  Very much 
 
20.   My cholesterol was too low. 
 
       Not at all                                  Very much 
 
21.    I was feeling too ill to take them. 
 
       Not at all                                  Very much 
 

 
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Appendix C: Interview Guides AIM 1 
Key Informant Interview Guide for Patients Living with HIV 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in learning more about your thoughts and 
beliefs about cardiovascular or heart disease. I am going to ask you some questions about these 
topics to hear about your experiences and perspectives. Please know that there is no right or 
wrong answer. You will notice that I won’t give you a lot of feedback on your responses because 
I don’t want to influence your answers. You may also notice that I will jot things down on paper 
while you talk- this is simply a reminder to ask you a follow-up question. Finally, you are under 
no obligation to talk about anything that you are not comfortable discussing with me. Do you 
have any questions or concerns before we begin? 
Primary Questions 
General CVD Perceptions 
Let’s start by you telling me about what you know about cardiovascular or heart disease. 
Prompts: What is heart disease; what causes heart disease; how do you prevent it; how do you 
treat it if you get it; how do you know if you have it? 
Do you think you are at risk for developing heart disease? Why? Prompts: Family history, past or 
current substance use, obesity, inactivity, diet, medications you take 
What do you know about the risk factors for stroke?  Are they similar or different from other 
heart disease risk factors?   
 
When you think about your passing, what do you think you will eventually die from? (e.g., 
AIDS, heart disease or something else) 
 
Have any of your doctors or nurses ever talked with you about heart disease? If yes, what did 
they tell you? Have you ever asked your HIV doctor about your risk of developing heart disease?  
Do you have a separate primary care doctor (from your HIV doctor)? If so, did have they ever 
talked with you your risk for heart disease?  
 
Have you ever been evaluated for heart disease by a doctor? If so, what did he or she do? Was it 
your HIV doctor or another doctor? What led to that evaluation (e.g., symptoms (chest pain, 
swelling, etc…) 
 
What are the medications that are used to prevent heart attacks and strokes?   

 
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Do you tend to be more worried about side-effects of medications or are you more worried about 
what will happen if you don’t take the medications?   
 
Tell me about a time when your doctor or nurse has talked with you about your risk for having a 
heart attack or heart problems? Probes: What prompted that discussion (e.g., did you bring it up, 
was it part of a research study, did you have abnormal blood pressure or cholesterol?) 
 
Have you been prescribed medications for blood pressure or cholesterol? Do you know what the 
medication is? How often to do you take it? What makes it hard to take it? Easy?  
 
Do you check your blood pressure at home or anywhere outside of a doctor’s office? If so, how 
often do you check it? 
 
What else do you do to help prevent heart problems? Who or what helps you do that?  
 
HIV and CVD  
Do you think HIV affects your risk for heart disease? If so, how?  
Has anyone in your doctor’s office ever talked with you about the relationship between HIV and 
heart disease? Who? What did they tell you? How did you respond to that conversation? Did it 
impact how you take care of yourself? How?  
What HIV medications are you taking? Have you ever heard that some HIV medications can 
increase your risk of developing heart disease while others do not impact this risk? Where and 
from whom? 
If you knew that HIV medication increases your heart disease risk, would this impact your 
behavior (e.g., smoking, diet, exercise, taking medications, seeing/talking with your doctor). 
Are you concerned about other medications interacting with your HIV drugs?  If a non-HIV 
doctor prescribes a medication for you, do you always check with your HIV doctor before you 
agree to take it?   
Would you be more likely to take a preventive medication (like aspirin or statins) if your HIV 
doctor prescribed it compared to a non-HIV provider?  Why or why not?   
 
Intervention Tailoring 
Tell me about a time you improved your health behavior. Who helped you achieve this 
improvement? What steps did you take to make the change? How long did it last? 

 
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Do you ever track anything at home, like your weight or your mood? What would make it easier 
for you to do so? What if we gave you a kit to monitor your blood pressure? Do you think you 
could measure it every day? What would be hard about that? What would make it easier?  
Other than your doctor, where do you get information about your health? What sources do you 
trust the most? What sorts of health messages or education do you prefer? What messages 
motivate or inspire you to change your health behaviors.  
What sort of intervention or program might help you improve heart disease prevention behaviors 
such as smoking cessation, eating a healthier diet, exercising harder and more often, talking with 
your doctor about how you can determine your own risk for heart disease and take steps to 
reduce that risk? 
Do you like messages that focus on one health behavior change (such as smoking cessation or 
improving you diet) or multiple changes?  
Do you prefer paper, verbal (conversations), digital (phone, computer) or visual (TV) messages 
to help you understand health information the best and how to best act on that information to 
improve your health? 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 
x 
Can you give me an example of a time when [significant statement] happened to you   
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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Key Informant Interview Guide for Clinicians 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in learning more about your thoughts and 
beliefs about cardiovascular disease among your HIV+ patients. We are most interested in the 
patients you see in their routine, outpatient HIV care, not those in the hospital. I am going to ask 
you some questions about these topics to hear about your experiences and perspectives. Please 
know that there is no right or wrong answer. You will notice that I won’t give you a lot of 
feedback on your responses because I don’t want to influence your answers. You may also notice 
that I will jot things down on paper while you talk- this is simply a reminder to ask you a follow-
up question. Finally, you are under no obligation to talk about anything that you are not 
comfortable discussing with me. Do you have any questions or concerns before we begin? 
Primary Questions for all Clinicians 
General CVD Perceptions 
x Let’s start by you telling me about what you think the biggest health problems are for your HIV+ 
patients.  
x Can you tell me what you know about cardiovascular or heart disease and HIV. Prompts: Are 
your HIV+ patients at risk for developing heart disease? Why? Prompts: Family history, past or 
current substance use, obesity, inactivity, diet, medications you take 
x When you think about your patients passing away, what do you think you will eventually die 
from? (e.g., AIDS, heart disease or something else) 
x Have you ever talked with your patients about heart disease? If yes, tell me about that/those 
conversation(s)? Prompts: What prompted that discussion (e.g., did you bring it up, was it part of 
a research study, did you have abnormal blood pressure or cholesterol?) Did they ask you about 
their risk of developing heart disease?  Did their primary care provider reach out to you? 
x What are the medications that are used to prevent heart attacks and strokes?   
x What can do you do to help prevent heart problems in your HIV+ patients? Who or what helps 
you do that?  
 
HIV and CVD  
x Do you think HIV affects your patient’s risk for heart disease? If so, how?  
x Have you ever heard that some HIV medications can increase your patient’s risk of developing 
heart disease while others do not impact this risk? Where and from whom?  
x How would knowing they are at increased risk for heart disease affect your patients’ health 
behavior (e.g., smoking, diet, exercise, taking medications, seeing/talking with your doctor). 
 

 
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Prescribing provider/pharmacist ONLY questions 
x What helps you think about or better manage CVD in your HIV+ patients? 
x Do you believe that your patients appropriately recognize their risk of heart disease?  If your 
high-risk patients recognize their risk, are they then motivated to address risk factors and take 
preventive actions?   
x What is your routine for monitoring cholesterol in your patients? 
x How often do you review current or past cholesterol results for your patients? Prompts: every 
visit?, once yearly?, rarely? 
x Blood pressure is typically measured at every clinical visit.  Do you ever neglect to review the 
blood pressure because you are focused on other things?  Do you ever notice the blood pressure 
is high but then decide that it is not a high enough priority to address at that visit?   
x How comfortable are you with current guidelines about the definitions and management of high 
blood pressure?   
x How comfortable do you feel prescribing hypertension and cholesterol medications and 
managing their side effects?  
x How often do you prescribe home blood pressure monitoring? How do you follow up on 
adherence to these medications or monitoring? Prompts: Have your nurse call; patient calls in 
with numbers; check in with patient via email or EMR reminders.   
x Do you talk with your patients about how HIV medications affect heart disease risk? If so, tell 
me about those conversations. 
x Do you believe drug-drug interactions is a significant barrier to prescribing preventive 
medications like statins?   
o HIV specialty providers: If a non-HIV doctor prescribes a medication for your 
patients, do you know about it? How frequently do you encounter dangerous drug-
drug interactions that result from others being unfamiliar with ART?   
o PCPs (i.e. non-HIV provider): How knowledgeable are you about ART drug 
interactions?  Do you avoid certain statin medications in all HIV patients for fear 
of drug interactions or do you check for specific interactions based on the patient’s 
ART? 
x Do you think your patients would be more likely to take a preventive medication (like aspirin or 
statins) if your HIV doctor prescribed it compared to a non-HIV provider?  Why or why not?   
x What types of patients do you refer to a specialist for cardiovascular disease prevention?  
Prompts: very high LDL or triglycerides (do you have a threshold)?  Difficult to control 
hypertension (do you have a threshold—i.e. not controlled on 3 meds? 5 meds?), + family 
history?, patient preference/request?   
x How comfortable are you ordering cardiovascular testing (i.e. stress tests, echocardiograms, 
holter/event monitors, coronary calcium scans)?  
 
Nurse and Medical Assistant ONLY questions 

 
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x Can you tell me when in the patient visit your patients’ blood pressure is assessed? What are the 
steps involved in measuring it? Is it logistically difficult for the patient to rest quietly for a time 
before it is taken? What makes this hard?  
x How often do you reconcile your patients’ medications? Do they ever have questions about their 
blood pressure and cholesterol medications? What sorts of questions do they ask? How do you 
address the questions?  
x Do you assess medication adherence? For which medications? Do you provide feedback to the 
patient based on the medication adherence levels? What do you do if they are non-adherent? If 
they are non-adherent to any of their medications do you follow up with them after their visit to 
see if its changed?   
 
Intervention Feasibly and Usability 
Finally, we are interested in designing a new initiative, with a new nurse coordinator, to help 
your patients reduce their risk of heart disease. However, we know in this and many clinics, there 
are cultural and systemic issues that can make a new clinic initiative more or less successful.  
We’d like to get your opinion on these issues and as a reminder, all information you provide will 
be confidential and aggregated across three clinics.  
System 
x Tell me about your clinic’s culture. What aspects of it help you do your job well and what 
aspects can make it harder for you? What are the strengths of your clinic? 
x Does your clinic have a hierarchy? If so, can you tell me how that affects how decisions are 
made in your clinic?  
x What the priorities of your clinic? Have they change over time? 
x Tell me about a clinic initiative that was recently developed to help your patients improve their 
health behavior. What steps were taken to help make the change? Who initiated the change and 
how did having that person champion it affect the initiative? How long did it last? What was the 
outcome (did it work)? 
Training 
x What sort of education or training do you prefer for new initiatives? Do you prefer paper, verbal 
(conversations), digital (phone, computer) or visual (TV) training? Individual or Group? Does 
continuing education credit entice you to complete new trainings? Would you be interested in 
helping to develop a new training for your clinic on reducing heart disease in your patients?  
 
Design Considerations/Representations 

 
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x When you have a patient concern, for example an elevated temperature or a high blood pressure, 
how does that information get turned into action in this clinic? Can you walk me through the 
various steps? [consider drawing this out on white board]. How do you involve non-HIV 
clinicians, for example your patient’s primary care provider, in this communication cycle? 
x How often do you personally communicate with your patients outside of the clinic setting? How 
does this communication happen (e.g., phone, EMR, via your nurse). Does the patient usually 
initiate this contact or do you?  
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 
x 
Can you give me an example of a time when [significant statement] happened to you   
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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COVID AIM: Key Informant Interview Guide for Patients Living 
with HIV 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in learning more about your thoughts and 
beliefs about how the coronavirus pandemic (or COVID-19) has impacted your cardiovascular 
health. I am going to ask you some questions about these topics to hear about your experiences 
and perspectives. Please know that there is no right or wrong answer. You will notice that I 
won’t give you a lot of feedback on your responses because I don’t want to influence your 
answers. You may also notice that I will jot things down on paper while you talk- this is simply a 
reminder to ask you a follow-up question. Finally, you are under no obligation to talk about 
anything that you are not comfortable discussing with me. Do you have any questions or 
concerns before we begin? 
Today’s date is:                                              and I am interviewing participant [use study ID] 
Primary Questions 
General COVID-19 Perceptions 
x Let’s start by you telling me about what you know about the novel coronavirus. 
Prompts: What is it; how do you prevent it; how do you treat it if you get it; how do you 
know if you have it?  
x Do you think you are at risk for becoming infected with coronavirus? Why? Prompts: 
Living situation, work, health care appointments, lack of social/material support? 
x Have any of your doctors or nurses ever talked with you about coronavirus? If yes, what 
did they tell you? Have you ever asked a doctor or nurse about how your HIV may 
impact your likelihood of becoming sick with coronavirus? What about your other risk 
factors such as heart disease or high blood pressure? 
x Have you ever been evaluated for coronavirus by a health care provider? If so, what did 
he or she do? Was it your HIV doctor or another doctor? What led to that evaluation (e.g., 
symptoms (chest pain, fever, etc…) 
 
Isolation 
 
x Tell me about your social interactions since word of coronavirus virus spread in March 
2020. Prompts: How often do you go outside of your house? Where do you go? How do 
you get there (e.g., walking, driving, public transportation, bicycle?) 
x Has this behavior changed over time (or X months since March 2020)? Why or Why not? 

 
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x Who do you talk to regularly on the phone or via computer? How has that changed over 
time? Who do you feel close to today?  
o Tell me about times when you have felt supported over the past X months?  
o Tell me about times when you have felt alone or isolated?  How has that affected 
your mood? Your health? Your motivation to take of your health? 
 
COVID and Self-Management 
Let’s talk a bit more about how any changes you have made to your behavior in response to 
COVID pandemic may have influenced your health. 
x What medications do you take for HIV? What about your heart health?  
x How has coronavirus affected your ability to take your medications? Prompts: Your 
schedule is different; motivation changed/diminished; unable to get refills/see your health 
care provider? You can’t travel to get your medications? 
x What else do you do to help manage your health? Physical activity, support groups, diet 
control, regularly clinic appointments, volunteer, read, take daily blood pressure 
measurements, etc? 
o How has this been impacted by the coronavirus? 
x Do you think the spread of coronavirus will impact your ability to take care of your HIV 
and heart disease over the long-term? How or why not? 
x Do you think it will impact your ability or willingness to visit your health care team? 
x What are your experiences with telehealth or talking to health care team over the phone 
or computer? Prompts: How comfortable are you? Does it change your relationship with 
the team? 
x What about doing more research visits on the computer or over the phone. Would you be 
willing to do that? What challenges do think you might encounter if you did more 
research visits over the phone or computer?  What benefits do you think might occur with 
more virtual research visits?  
x If we were change EXTRA-CVD to include more virtual visits/calls, what should we 
keep in mind? Prompts: Internet access? Ability to navigate platforms? Should we have 
an orientation visit first to make sure you understand the technology?  
x How about the social support you receive form the research team. How could that be 
effected by fewer in person visits? 
x Do you think more virtual visits would impact your willingness to participate in EXTRA-
CVD and other research studies? If so, how could we offset that? 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  

 
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[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 
x 
Can you give me an example of a time when [significant statement] happened to you   
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 
 

 
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Appendix D: Clinic Variables Checklist 
EXTRA-CVD 
Clinic Variables Checklist 
Date: _____________________________ 
Study site (circle one): 
UH/SIU 
MetroHealth  
Duke 
Instructions: For each of the following support services, please circle the option that best 
describes availability of that services in your ID or HIV clinic. 
Resources 
Not Available 
Same Day 
Availability 
Available by Advance 
Scheduling/Request 
Only  
Adherence Support Services (Ex. 
Assisted pill box filling, DOTS, 
etc.) 
0 
1 
2 
CVD Prevention 
Specialist/Consultant with HIV 
Expertise 
0 
1 
2 
Dietician/Nutritionist  
0 
1 
2 
Exercise or Fitness Classes 
0 
1 
2 
Medication Adherence Incentive 
Programs 
0 
1 
2 
Nurse Support Line 
0 
1 
2 
Peer Coaching 
0 
1 
2 
Pharmacist  
0 
1 
2 
Social Worker Led Support 
Group(s) 
0 
1 
2 
Tobacco Cessation Program 
0 
1 
2 
Transportation Vouchers 
0 
1 
2 
 
 
 
 
 
 
 
 
What additional in-clinic resources are available to aid patients in managing their hypertension 
and/or hyperlipidemia? 
_________________________________________________________________________________ 
_________________________________________________________________________________ 
 
 

 
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Appendix E: PLHIV Pilot Participant Acceptability Testing 
Guide 
Note: Not all questions will be asked explicitly. Participants may answer the questions, or cover 
the topic, in the course of the one-on-one conversation.  
Study background 
Welcome to our discussion! People living with HIV (PLHIV) are at increased risk for heart 
disease; however, the uptake of evidence based therapies to prevent heart disease is substandard. 
As such, strategies to improve the uptake of cardiovascular disease preventive therapies among 
PLHIVs are urgently needed.  The goal of this study is to test a prevention, nurse-led 
intervention to extend the HIV/AIDS treatment cascade for the treatment of hypertension and 
high cholesterol among PLHIV on suppressive antiretroviral therapy.  
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with me today. I am interested in learning more about your thoughts and 
beliefs about cardiovascular disease among your HIV+ patients. I am most interested in your 
thoughts about a new intervention our research team is planning on scaling-up at your clinic and 
for your HIV+ patients who have hypertension and high cholesterol. I am going to ask you some 
questions about these topics to hear about your experiences and perspectives. Please know that 
there is no right or wrong answer.  
Here are the ground rules for our focus group discussion. We would like to have everyone 
participate in this discussion. I will only give you all a few probes and would like for you all to 
react to those probes. Beyond giving the probes, the discussion will be entirely driven by you all 
– my only job is to facilitate. And I will facilitate to get more clarity on statements you all share. 
Additionally, I am interested in engaging each of you to talk freely and to make sure everyone 
has equal opportunities to speak. My main purpose here is to ask questions, listen, and make sure 
that you have the opportunity to share your thoughts and perspectives. This session is being 
recorded, as was noted in the consent form you signed before, so that none of your informative 
comments and feedback will be missed. Again your names will not be collected and your 
comments will be confidential. Finally, you are under no obligation to talk about anything that 
you are not comfortable discussing with me. Do you have any questions or concerns before we 
begin? 
[Facilitator, please note the participant’s ID number in the audio recording so we can match it to 
the demographic information.] 
Intervention Acceptability 
Finally, we are interested in a new initiative, with a new nurse coordinator - led intervention, that 
we designed to help patients like you reduce their risk of heart disease in clinics around the 

 
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country. As such we would like to get your opinion on thoughts on this intervention.  As a 
reminder, all information you provide will be confidential and aggregated across three clinics.  
Facilitators and barriers to the nurse-led intervention for HIV+ patients with hypertension and 
high cholesterol 
1. Please tell me your thoughts on working with your CVD nurse to tailor treatment for 
HIV+ patients like yourself who have either been diagnosed with hypertension and high 
cholesterol.  
a. PROBE: What general experience do you have working with nurses to manage 
your health? 
2. What do you think are some potential benefits or barriers of working with nurses? 
 
[Interviewer will share the refined intervention structure and format with the participant(s).] 
Thoughts on logistical factors (i.e. resources or tools at that clinic)  
3. What are your initial thoughts on this intervention? 
4. Do you like this intervention? 
5. Please tell me any potential concerns you may have as an HIV+ patient participating in 
this intervention? 
6. What are some potential benefits that you see with integrating this intervention into your 
current treatment? 
7. What are some current resources or tools within your clinic that you think will help 
facilitate the integration of this intervention for your care? 
a. Conversely, what may be some aspects of your clinic that you think will be a 
barrier to integrating this intervention for your care or treatment? 
8. Do you feel that this intervention is relevant in terms of your health or the issues you are 
dealing with? 
9. Would you be interested in having this service offered to you as part of your treatment? 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
• 
Can you tell me more about that?  
• 
Can you tell me more about how that affects [X] 
• 
Can you clarify what you mean by [significant statement] 
• 
Can you give me an example of a time when [significant statement] happened to you   
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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Appendix F: PLHIV Pilot Participant Feasibility Testing 
Guide 
Note: Not all questions will be asked explicitly. Participants may answer the questions, or cover 
the topic, in the course of the one-on-one conversation.  
Study background 
Welcome to our discussion! People living with HIV (PLHIV) are at increased risk of heart 
disease; however, the use of the most effective treatment options or approaches to manage heart 
disease in this population is not the best. As such, strategies to improve the uptake of heart 
disease prevention among PLHIVs is very important and needed in HIV clinics. The goal of this 
study is to test a prevention, nurse-led intervention to extend the HIV/AIDS treatment cascade 
for the treatment of hypertension and high cholesterol among PLHIV on suppressive 
antiretroviral therapy.  
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with me today. I am interested in learning more about your thoughts and 
beliefs about cardiovascular disease among your HIV+ patients. I am most interested in your 
thoughts about a new intervention our research team is planning on scaling-up at your clinic and 
for your HIV+ patients who have hypertension and high cholesterol. I am going to ask you some 
questions about these topics to hear about your experiences and perspectives. Please know that 
there is no right or wrong answer.  
Here are the ground rules for our focus group discussion. We would like to have everyone 
participate in this discussion. I will only give you all a few probes and would like for you all to 
react to those probes. Beyond giving the probes, the discussion will be entirely driven by you all 
– my only job is to facilitate. And I will facilitate to get more clarity on statements you all share. 
Additionally, I am interested in engaging each of you to talk freely and to make sure everyone 
has equal opportunities to speak. My main purpose here is to ask questions, listen, and make sure 
that you have the opportunity to share your thoughts and perspectives. This session is being 
recorded, as was noted in the consent form you signed before, so that none of your informative 
comments and feedback will be missed. Again your names will not be collected and your 
comments will be confidential. Finally, you are under no obligation to talk about anything that 
you are not comfortable discussing with me. Do you have any questions or concerns before we 
begin? 
 
[Facilitator, please note the participant’s ID number in the audio recording so we can match it to 
the demographic information.] 
Intervention Feasibility 

 
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We are interested your experience and thoughts have participated in the pilot test for the new 
nurse coordinator-led intervention that we designed to help your patients reduce their risk of 
heart disease in clinics around the country. As a reminder, all information you provide will be 
confidential and aggregated across three clinics.  
Participating in the nurse-led intervention for HIV+ patients with hypertension and high 
cholesterol: 
1. Please tell me what your general thoughts and experience was with the nurse-led 
intervention?  
2. What effect (positive or otherwise) did the intervention have on how you engaged with 
the following providers: 
a. Prevention nurse: How did you interactions with the nurse evolve over the course 
of the 6-week pilot? 
b. Your primary HIV nurse: Did your participation in this pilot affect your 
relationship with your primary HIV nurse? If so, how? 
c. Your physician providers: How did your participation in this pilot affect your 
relationship with your primary HIV doctor and/or your primary care doctor? 
3. After meeting with your nurse during the intervention what differences did you notice in 
how you responded to your own treatment? 
a. PROBE: How where you better able to treat or care for your hypertension and 
cholesterol?  
 
Thoughts on intervention’s feasibility  
4. How do you feel this intervention fits within your clinic setting? 
5. After completing all of the intervention-related meetings with the nurse, what barriers did 
you feel that they faced in helping you manage your hypertension and cholesterol? 
6. In what ways do you think this intervention, in its current form, will be an effective tool 
or resource for your clinic to integrate going forward? 
7. In what ways do you think this intervention, in its current form, will NOT be an effective 
tool or resource for your clinic to integrate going forward? 
8. What feedback have you shared or provided about the intervention with the clinic 
supervisors or nurses?  
9. Does this intervention seem possible as a form of HIV treatment or management for 
people with hypertension and high cholesterol? 
10. How do you think this intervention can be implemented within general HIV care clinics?  
 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
• 
Can you tell me more about that?  
• 
Can you tell me more about how that affects [X] 
• 
Can you clarify what you mean by [significant statement] 
• 
Can you give me an example of a time when [significant statement] happened to you   
 

 
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Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information. 
 

 
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Appendix G: Health Worker Feasibility Testing Guide 
Note: Not all questions will be asked explicitly. Participants may answer the questions, or cover 
the topic, in the course of the one-on-one conversation.  
 
Study background 
Welcome to our discussion! People living with HIV (PLHIV) are at increased risk for heart 
disease; however, the uptake of evidence based therapies to prevent heart disease is substandard. 
As such, strategies to improve the uptake of cardiovascular disease preventive therapies among 
PLHIVs are urgently needed. The goal of this study is to test a prevention, nurse-led intervention 
to extend the HIV/AIDS treatment cascade for the treatment of hypertension and high cholesterol 
among PLHIV on suppressive antiretroviral therapy.  
 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with me today. I am interested in learning more about your thoughts and 
beliefs about cardiovascular disease among your HIV+ patients. I am most interested in your 
thoughts about a new intervention our research team is planning on scaling-up at your clinic and 
for your HIV+ patients who either have or at risk for CVD. I am going to ask you some 
questions about these topics to hear about your experiences and perspectives. Please know that 
there is no right or wrong answer.  
 
Here are the ground rules for this semi-structured interview. I am going to ask you a few 
questions and will only give you a few probes with the intention that you will react to those 
probes. Beyond giving the probes, the discussion will be entirely driven by your responses – my 
only job is to facilitate. And I will facilitate to get more clarity on statements you share. 
Additionally, I am interested in engaging each you to talk freely and to make sure you are able to 
share your thoughts fully. My main purpose here is to ask questions, listen, and make sure that 
you have the opportunity to share your thoughts and perspectives. This session is being recorded, 
as was noted in the consent form you signed before, so that none of your informative comments 
and feedback will be missed. Again your name will not be collected and your comments will be 
confidential. Finally, you are under no obligation to talk about anything that you are not 
comfortable discussing with me. Do you have any questions or concerns before we begin? 
 
[Facilitator, please note the participant’s ID number in the audio recording so we can match it to 
the demographic information.] 
Intervention Feasibility 
We are interested your experience and thoughts have participated in the pilot test for the new 
nurse coordinator-led intervention that we designed to help your patients reduce their risk of 
heart disease in clinics around the country. As a reminder, all information you provide will be 
confidential and aggregated across three clinics.  
 
Participating in the nurse-led intervention for HIV+ patients with hypertension and cholesterol 
1. Please tell me about your thoughts and experience with the nurse-led intervention?  
2. How did the intervention impact (positive or otherwise) the way in which you engaged 
with HIV+ patients?  

 
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3. Did you feel prepared to integrate the intervention in your current treatment routine? If 
so, how? If not, what would have helped you to be more prepared? 
4. After meeting with your patients during the intervention, what were some differences you 
noticed in how patients responded to their treatment? 
a. PROBE: How where patients better able to treat or care for their CVD risks? 
 
Thoughts on the intervention’s feasibility 
5. How do you feel this intervention fits within your clinic setting? 
6. After completing all of the intervention procedures with your patients, did you feel that 
they still faced any barriers to managing their hypertension and cholesterol? 
7. How did this intervention impact your workload with treating HIV+ patients? 
8. In what ways do you think this intervention, in its current form, will be an effective tool 
or resource for your clinic to integrate going forward? In other words, what worked well 
in this intervention in this particular setting? 
9. In what ways do you think this intervention, in its current form, will NOT be an effective 
tool or resource for your clinic to integrate going forward? Or what can be improved?  
10. What feedback have you shared or provided about the intervention with your clinic 
colleagues?  
11. Does this intervention seem possible as a form of HIV treatment or management for 
people with hypertension and high cholesterol? 
12. How do you think this intervention can be implemented within general HIV care clinics?  
 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
• 
Can you tell me more about that?  
• 
Can you tell me more about how that affects [X] 
• 
Can you clarify what you mean by [significant statement] 
• 
Can you give me an example of a time when [significant statement] happened to you   
 
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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Appendix H: Design Team Discussion Guide 
Themes to be assessed: 
x Previous design team experience. 
x Understanding of the design team approach. 
x Thoughts on the design team process for the nurse-led intervention. 
x Experience for each phase or meeting of the design approach. 
x Thoughts on the final intervention model. 
 
General focus group discussion introduction: 
For this part of our design team meeting, I am most interested in learning more about your 
thoughts and beliefs about the human-centered design process. I am going to ask you some 
questions about the process to hear about your experiences and perspectives. Please know that 
there is no right or wrong answer.  
Here are the ground rules for our focus group discussion. We would like to have everyone 
participate in this discussion. I will only give you all a few probes and would like for you all to 
react to those probes. Beyond giving the probes, the discussion will be entirely driven by you all 
– my only job is to facilitate. And I will facilitate to get more clarity on statements you all share. 
Additionally, I am interested in engaging each of you to talk freely and to make sure everyone 
has equal opportunities to speak. My main purpose here is to ask questions, listen, and make sure 
that you have the opportunity to share your thoughts and perspectives. This session is being 
recorded, as was noted in the consent form you signed before, so that none of your informative 
comments and feedback will be missed. Again your names will not be collected and your 
comments will be kept confidential, not to be revealed to anyone outside of this room. Finally, 
you are under no obligation to talk about anything that you are not comfortable discussing with 
me. Do you have any questions or concerns before we begin? 
Focus group questions 
x What impact do you think your individual participation in the design team had on the 
final intervention model? 
x Tell me about your experiences working on a team with individuals from different 
professions and roles? 
x What was your personal contribution and the overall team’s contribution to the design 
team?  
x Was there a particular design phase (i.e. brainstorming, conceptualization, creation, 
iteration I, or iteration II) that you found to be most insightful for the entire design 
experience? Why or why not? 
x Which design phase (i.e. brainstorming, conceptualization, creation, iteration I, or 
iteration II) did you find to be most challenging and why do you think so?  
x Which design phase (i.e. brainstorming, conceptualization, creation, iteration I, or 
iteration II) did you find to be least challenging and why do you think so?  

 
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x What are your general thoughts on the final intervention model? Do you think that 
this version will meet the intended goals of our design team and that of the research 
study? 
x Are there any closing thoughts that you want to share or that you think we should 
have discussed in terms of the final intervention model that we do not touch on?  
x Are there any final thoughts that you want to share or that you think we should have 
discussed in terms of the design team experience that we do not touch on?  
Thank you for your time and participation. We very much appreciate your comments, 
discussions, and input throughout the design process.  
 
 

 
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Appendix I: Trust and Communication Survey (PLHIV 
participant – Provider) 
As a participant in the EXTRA-CVD study, we are asking you to complete a survey about your 
relationship with your healthcare providers. You will need at least 15 minutes of uninterrupted 
time to take this survey. If you have any questions, please see your EXTRA-CVD nurse or study 
coordinator.  Please understand that your answers will be confidential.  More specifically, your 
name and the names of your providers will never be recorded with your data.  The unique ID 
numbers will be kept separately by study staff at your site who do not have access to the survey 
results.  Please respond below in order to proceed:  
o Yes I understand my rights as a participant in this study. I consent to proceed.  
o No I do not consent and will not participate in this study and survey  
 
Please enter here your unique participant ID. EXTRA-CVD study staff will ensure that you enter 
your correct ID.  PLEASE DO NOT LIST YOUR NAME.  
________________________________________________________________ 
 
Please select which visit you completed today as part of this study. EXTRA-CVD study staff will 
ensure that you select the correct answer. 
o Baseline visit  
o 4 months visit  
o 8 months visit  
o 12 months visit  
 
As a participant of this study, in the following sections, you will be asked some questions 
regarding your relationships with providers that may help treat your HIV or your blood pressure 
and cholesterol.  At a minimum, this will include: your HIV provider and your EXTRA-CVD 
nurse.   
 
Additionally, you may be asked some questions about the rest of your health care providers (for 
example, your Primary care physician, your HIV clinic nurse or you Non-HIV specialists).  
 

 
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We hope to collect quality data for our research. But If you feel uncomfortable to answer any of 
the questions  or feel that a question if not applicable to you, feel free to skip it.  
Do you have a HIV clinic nurse? 
o Yes  
o No  
 
Do you have a Primary care physician? 
o Yes  
o No  
 
Please indicate which of the following medical professionals primarily treats your blood pressure 
(if multiple physicians care equally for your blood pressure, please select all that apply): 
  My HIV provider  
  My HIV clinic nurse  
  My Primary care physician  
  My Non-HIV specialist, please specify the specialist type (i.e.; cardiologist, 
nephrologist, endocrinologist): ________________________________________________ 
  No one manages my blood pressure  
 
Please indicate which of the following medical professionals primarily treats your cholesterol (if 
multiple physicians care equally for your cholesterol, please select all that apply): 
  My HIV provider  
  My HIV clinic nurse  
  My Primary care physician  

 
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  The same Non-HIV specialist who also treats my blood cholesterol (as indicated in the 
question above)  
  A different  Non-HIV specialist from whom treats my blood cholesterol as indicated in 
the prior question), please then specify the specialist type- i.e. cardiologist, nephrologist, 
endocrinologist): ________________________________________________ 
 No one manages my cholesterol  
 
*** The participant will complete the following survey items for each of their providers 
identified above.   
Please think of your relationship with your [HIV, PCP, non-HIV specialist] provider. For the 
validity of this study, please answer honestly. Recall your answers are confidential and will  
never be shared with this provider nor anyone else outside our research team.  Some of the 
questions may sound repetitive, please do read fully before answering each question.  
How long have you been a patient of this provider? 
o I just became a patient this past month  
o Less than 6 months  
o 6 months to 1 year  
o 1-2 years  
o 3-5 years  
o More than  5 years  
 
How often do you communicate with this provider? 
o Every 1-2 months  
o Every 3-4 months  

 
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o Every 5-6 months  
o Once yearly  
 
Please rate the following statements based on your recent visits with this provider and overall 
care with this provider. 
 
Strongly 
Disagree 
Disagree 
Neither 
Agree nor 
Disagree 
Agree 
Strongly 
Agree 
My provider has much knowledge 
about the treatment that needs to 
be done.  
o  
o  
o  
o 
o  
My provider is very concerned 
about my welfare.  
o  
o  
o  
o 
o  
I feel I can discuss with my 
provider how I honestly feel about 
my health treatment,  even 
negative feelings and frustration.  
o  
o  
o  
o 
o  
Overall, I trust my provider.  
o  
o  
o  
o 
o  
 
 
Strongly 
Disagree 
Disagree Neither Agree 
nor Disagree 
Agree 
Strongly 
Agree 
My provider and I 
communicate effectively.  
o  
o  
o  
o 
o  
My provider listens carefully to 
me.  
o  
o  
o  
o 
o  
Overall, I am satisfied with the  
communication with my 
provider.  
o  
o  
o  
o 
o  
 
 

 
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. 
 
Strongly 
Disagree 
Disagree 
Neither 
Agree nor 
Disagree 
Agree 
Strongly 
Agree 
My provider and I have a good 
relationship.  
o  
o  
o  
o 
o  
I feel part of a team with my 
provider in regards to my health 
care and needs.  
o  
o  
o  
o 
o  
Overall, I like my provider.  
o  
o  
o  
o 
o  
Overall, I am satisfied with my 
provider.  
o  
o  
o  
o 
o  
 
 
Do you have any recommendations to improve your care experience with this provider? 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
 
 
 
 
 

 
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Appendix J: Trust and Communication Survey (Prevention 
RN – PLHIV participant) 
Enter the participant ID 
________________________________________________________________ 
 
Please indicate the study visit: 
o Baseline visit  (0)  
o 4 month visit  (1)  
o 8 month visit  (2)  
o 12 month visit  (3)  
 
Please think of your relationship with the patient you listed above. For the validity of this 
study, please answer honestly. Recall your answers are confidential and will never be shared 
with any provider, patient nor anyone else outside our research team.  Some of the questions may 
sound repetitive, but please read fully before answering each question.  
Please rate the following statements based on your recent interaction with this patient. 
 
Strongly 
Disagree 
(1) 
Disagree 
(2) 
Neither Agree 
nor Disagree 
(3) 
Agree 
(4) 
Strongly 
Agree (5) 
Overall, I trust this patient.  
o  
o  
o  
o  
o  
Overall, I am satisfied with 
my communication with 
this patient  
o  
o  
o  
o  
o  
Overall, I have a good 
relationship with this 
patient.  
o  
o  
o  
o  
o  
 
Thank you! To rate another participant, please open a new survey.   
 
 

 
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Appendix K: Trust and Communication Survey (Prevention 
RN – Provider) 
Please input only the unique identifier of the provider (do not enter any names!) that you will be 
rating in the next set of questions. Please verify this ID is correct before continuing. 
________________________________________________________________ 
 
Please rate the following statements based on your recent interactions (since the last survey) with 
this provider.  Your responses to these questions may or may not change over time as you 
continue to interact with this provider over the course of the EXTRA-CVD intervention. 
 
Strongly 
Disagree 
Disagree 
Neither Agree 
nor Disagree 
Agree 
Strongly 
Agree 
Overall, I trust this provider. 
o  
o  
o  
o 
o  
Overall, I am satisfied with the 
communication with this 
provider. 
o  
o  
o  
o 
o  
Overall, I have a good 
relationship with this provider. 
o  
o  
o  
o 
o  
 
Do you have another provider to rate? 
o Yes 
o No 
 
 
 

 
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Appendix L: Study staff and prevention nurse observation 
checklist to ensure intervention fidelity. 
 
Study Staff Observation Checklist: 
Date: 
Observer:  
Location:  
 
Setup: 
 Checked that Blood Pressure (BP) machines are functional and available 
 Knew the directions to the blood lab and the working hours 
 
Explain and correctly perform blood pressure procedures (study staff NOT prevention nurse): 
 Participant was sitting with feet on the floor 
 Participant’s arm was at heart level 
 Participant removed extra clothing (coat/jacket must be removed; long sleeve shirts may 
remain on) 
 Participant was encouraged to relax 
 Participant was not talking during measurement 
o If participant was talking, measurement was repeated 
 BP cuff was well placed above the elbow and admitting two fingers 
 Correct size of BP cuff was used 
 Two BPs were obtained, 1 minute apart 
 Blood pressure was checked in both arms 
 
Informed consent: 
 Explained purpose of research study 

 
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 Explained description of procedure 
 Explained confidentiality of study data 
 Explained potential benefits 
 Explained potential risks 
 Explained voluntary participation and rights to discontinuation 
 Checked understanding with open questions. “Could you tell me what’s going to happen 
if you enroll in the study?”)  
 Checked understanding with closed questions  (e.g. “Will you get free medications from 
the staff of this research study?” or “what will happen to your medical care after the 
study?” 
 Corrected misconceptions  (eg: Patient thinks they will get free medications or patient 
thinks they don’t have to follow up with their doctor after this study is done”) and 
recheck understanding.  
 Filled the informed consent checklist  
 Requested signature or participant thumbprint 
 Asked if participant has any questions 
 
Data collection: 
 Explained how to use REDCap to the participant 
 Appropriately gathered medical history data from chart review 
 Appropriately answered questions about how to respond to individual survey questions 
 
 
 

 
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Prevention nurse procedures checklist: 
Date: 
Observer:  
Location:  
 
Establishing Rapport: 
 Introduced herself/ himself to the patient 
 Made eye contact with the patient 
 Listened to the patient 
 Was able to engage patient in the conversation 
 
Counselling: Baseline 
 Asked patient for the purpose and side effects of his/her current medications 
 If a new medication is added, PN discussed purpose and side effects of the medication, 
and any required follow up  
 Discussed strategies for medication adherence 
 Discussed non pharmacological targets for blood pressure control  
 Asked patient for their preferred primary provider  
 Discussed methods of home BP monitoring 
 Set expectations with the patient about follow up phone calls and visits 
 Informed primary and non primary providers of plan at the end of visit 
 
Counselling: Follow up 
 Asked patient for home BP values over the last 2 weeks 
 Checked patient’s understanding of the method of home BP measurement.  
 Reviewed patient’s medication list and adherence 
 If patient is non- adherent, prevention nurse discussed reasons for non-adherence (Eg. 
side effects, cost, timing etc. ) 

 
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 If a new medication is added, prevention nurse discussed purpose and side effects of the 
medication, and any required follow up  
 Referred patient to the blood lab for a lipid panel 
 Set expectations for follow up phone call and visits 
 Informed primary provider and non primary provider of updated plan 

 
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Appendix M: Behavior Change Counseling Index (BECCI) 
to Measure Practitioner’s Motivational Interviewing Skills 
  
Date:  
Staff and Role:  
Observer:  
Strengths: 
 
Area for Growth: 
 
 
Scoring: 0 = Not at all, 1 = 
Minimally, 2 = To some 
extent, 3 = A good deal, 4 = A 
great extent, or N/A 
Item 
Description 
Score 
N/A 
Comments 
1. 
Invites the person to talk 
about behavior change* 
Explicitly asks permission to talk about behavior 
change. Conveys person is not obligated to make 
a decision.  
  
 
 
x  
2. 
Demonstrates sensitivity 
to talking about other 
issues 
Person is given choice in what to talk about; use 
of agenda setting. 
 
 
x  
3. 
Encourages person to 
talk about current 
behavior/status quo 
Encourages person to talk freely about the 
benefits and limitations of current behavior. Uses 
open-ended questions to elicit person’s 
perspective and reflections to convey 
understanding. 
 
 
x  
4. 
Encourages person to 
talk about change 
Encourages person to talk freely about the 
benefits and limitations of making a behavior 
change. Uses of open-ended questions to elicit 
person’s perspective and reflections to convey 
understanding. 
 
 
x  
5. 
Asks questions to elicit 
how person thinks and 
feels about topic 
Uses open-ended questions to elicit person’s 
thoughts and feelings related to a behavior 
change 
 
 
[Closed Questions – 
CQ] 
x  
 
 
 
 
 
 
 
[Open Questions – 
OQ] 
x  

 
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6. 
Uses reflective listening 
when the person talks 
about the topic 
Uses reflections to convey understanding, clarify 
understanding of what the person has said and 
encourage further patient elaboration. 
 
 
x  
7. 
Uses summaries to bring 
together what the person 
says about the topic 
Uses periodic summaries (collecting, linking, 
transitional) to check understanding, assists 
person to hear what they have said and/or 
transition to a new task (i.e., change planning) 
 
 
x  
8. 
Acknowledge challenges 
about behavior change 
that the person faces 
Uses reflections to convey understanding that 
change is difficult and affirm the person’s 
strengths 
 
 
x  
9. 
When providing 
information it is sensitive 
to person’s concerns and 
understanding* 
Attempts to understand what the person knows, 
wants to know and elicits their understanding of 
information provided and/or reaction to 
information provided. N/A if no information 
requested or shared 
 
 
x  
10. Staff and person 
exchange ideas about 
how the person could 
change current behavior* 
Uses open-ended questions to encourage person 
to brainstorm strategies that support behavior 
change; person offers most of the ideas; 
permission to disregard and multiple ideas are 
offered when staff makes suggestions. N/A if 
person is not ready to plan for change  
 
 
x  
BECCI Overall (Average) Score 
 
 
 
11. Staff speaks for 
approximately 
x More than half the time 
x About half the time 
x Less than half the time 
x  
 
 
 
 
 
 
 
 

 
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MI Skill Development Plan 
Name: 
 
 
 
 
                      Date:  
Strengths Demonstrated in Session 
 
 Skill Development 
MI Skill Targeted 
for Improvement 
What specifically 
will be developed 
or improved? 
How will the goal be reached? 
 
 

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Appendix O. Functional Assessment of Currently Employed 
Technology Scale (FACETS), Copyright 201 Charles M. 
Lepkowsky, Ph.D 
 
 

 
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Appendix P. Virtual Communication Preferences Form 
Person Completing this Form:  
Name  _________________________________________  
Role ___________________________________________  
  
Basic Information  
First Name:  _______________________________Enrollment Date: ___________________  
Preferred Name:  ___________________________MRN:  ____________________________ 
Last Name:  _______________________________Study ID:  _________________________  
  
Contact Information  
a) Which of the following would you like us to use to get in touch with you (circle all that apply)?  
i. Phone              
    Text                 E-mail  
 
b) What is the best telephone number to reach you?   
( ___ ___ ___ ) ___ ___ ___ - ___ ___ ___ ___   
 
c) Is there a next best phone number to reach you?   
( ___ ___ ___ ) ___ ___ ___ - ___ ___ ___ ___   
 
d) What days of the week are best for us to reach you?  ___________________________  
 
e) What is the best time of the day to reach you? _________________________________  
 
f) 
Will you be the only person answering these phone numbers?  If not, how do you want us to 
identify ourselves? 
 
g) Please rate your skills in this area by selecting the most appropriate answer for each 
statement.    
  
Can you:  
  
  
I’m not sure 
what this 
means  
I haven’t 
done this  
I did this 
once  
I do this 
regularly  
I could teach 
someone else 
how to do this  
Email  
Send an email to one 
or more people?  
¨  
¨  
¨  
¨  
¨  
Open and/or save an 
attachment from a 
received email?  
¨  
¨  
¨  
¨  
¨  
Text  
Open a text message 
from someone on your 
phone   
¨  
¨  
¨  
¨  
¨  

 
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Send a text message 
on your phone to one 
or more people  
¨  
¨  
¨  
¨  
¨  
Browsing the internet  
Open a website link   
¨  
¨  
¨  
¨  
¨  
Copy and paste a 
website link  
¨  
¨  
¨  
¨  
¨  
FaceTime  
Accept or send a 
FaceTime request to 
communicate with 
people on video  
¨  
¨  
¨  
¨  
¨  
Zoom Video Conference  
Open a zoom meeting 
invite from your email  
¨  
¨  
¨  
¨  
¨  
Communicate with a 
health care provider 
on zoom   
¨  
¨  
¨  
¨  
¨  
  
h. How comfortable are you with communicating about your health on zoom/FaceTime or other 
video platform? (please circle one)  
  
1         2         3          4          5          6          7          8          9          10   
  
 Not comfortable at all                                                                       Very Comfortable   
  
i. 
How concerned would you be about your living space when communicating with a provider on 
video? (please circle one)  
  
 1          2          3          4          5          6          7          8          9          10   
  
Not comfortable at all                                                                       Very Comfortable   
  
j. 
How concerned would you be about confidentiality or being overheard when communicating 
with a provider on video? (please circle one) 
 
 1          2          3          4          5          6          7          8          9          10   
  
Not comfortable at all                                                                       Very Comfortable   
 
k. Please rank your preference for communication with the EXTRA-CVD nurse (1 being the most 
preferred choice):   
Telephone (no video):  _______  
Zoom:                        _______  
FaceTime:             _______  
Other:             _______  
  

 
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k. Do you have concerns about communicating with the EXTRA-CVD intervention nurse on any of 
the platforms mentioned above? Please explain.   
 

 
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APPENDIX Q: AAIM-High Observation Checklist 
  
Date: 
Observer: 
Location: 
  
What was the platform used by the nurse and participant for the observed study visit? 
o Zoom 
o FaceTime 
o Telephone visit 
o In-person consent 
o Other: ___________ 
  
What type of study visits was observed? 
o Consent visit 
o Baseline visit 
o 4-month follow-up visit 
o 8-month follow-up visit 
o Final 12-month visit 
o Interim check-in (not a quarterly follow-up visit) 
o Other: ___________ 
  
Did the observer observe in real time or observe to a recorded session?  
o Live session 
o Recorded 
  
(If Live) Live setup:  
o Observer and nurse join Zoom room or telephone call prior to participant visit  
o Prevention nurse introduces observer (if applicable) and purpose  
  
(If Recorded) Recorded session:  
o Prevention nurse obtains verbal consent prior to recording  
o Prevention nurse begins recording session (use tape recorder if telephone visit and Zoom 
recording feature if Zoom visit) 

 
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Data collection (All but consent visit).   
 Ensure participant correctly performs a home BP measurement (check all that apply): 
o Participant was sitting with feet on the floor 
o Participant’s arm was at heart level 
o Participant removed extra clothing (coat/jacket must be removed; long sleeve shirts may remain 
on) 
o Participant relaxed for five minutes 
o Participant was not talking during measurement 
o If participant was talking, prevention nurse encouraged participant to repeat measurement 
o BP cuff was well placed above the elbow and admitting two fingers 
  
Did the prevention nurse provide any coaching to the patient regarding blood pressure procedures?  
o Yes (Explain: _____________________) 
o No  
  
Data collection: 
o Appropriately gathered medical history data from chart review 
  
Is the participant completing surveys independently using REDCap?  
o Yes 
o No 
 
  
 
If yes:  
o Explained how to use REDCap to the participant  
o Appropriately answered questions about how to respond to individual survey questions 
 
  
 
If no:  
o Read questions to the participant verbatim 
o Appropriately answered questions about how to respond to individual survey questions 
 
 
  

 
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Counseling (all but consent visit) 
 Establishing Rapport: 
o Made an effort to affirm the patient virtually by nodding, active listening, etc.  
o Listened to the patient 
o Was able to engage patient in the conversation 
  
Counselling: Baseline 
o Asked patient for the purpose and side effects of current medications 
o If a new medication is added, PN discussed purpose and side effects of the medication, and any 
required follow up  
o Discussed strategies for medication adherence 
o Discussed non pharmacological targets for blood pressure control  
o Asked patient for their preferred primary provider  
o Discussed methods of home BP monitoring 
o Assessed comfort and provided coaching on technology 
o Provided troubleshooting for technology issues 
o Set expectations with the patient about follow up phone calls and visits 
o Informed primary and non primary providers of plan at the end of visit 
  
Counselling: Follow up 
o Asked patient for home BP values over the last 2 weeks 
o Checked patient’s understanding of the method of home BP measurement.  
o Reviewed patient’s medication list and adherence 
o If patient is non- adherent, prevention nurse discussed reasons for non-adherence (Eg. side 
effects, cost, timing etc. ) 
o If a new medication is added, prevention nurse discussed purpose and side effects of the 
medication, and any required follow up  
o Assessed comfort and provided coaching on technology 
o Provided troubleshooting for technology issues 
o Set expectations for follow up phone call and visits 
o Informed primary provider and non primary provider of updated plan 
  
 
 

 
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Consent Visit (consent visit only) 
Communication Preferences: 
o Appropriately obtains communication preferences and engages in conversation about 
technology  
Informed consent: 
o Explained purpose of research study 
o Explained description of procedures 
o Explained confidentiality of study data 
o Explained potential benefits 
o Explained potential risks 
o Explained voluntary participation and rights to discontinuation 
o Checked understanding with open questions. (“Tell me what’s going to happen if you enroll in 
the study.”)  
o Checked understanding with closed questions (e.g. “Will you get free medications from the staff 
of this research study?” or “what will happen to your medical care after the study?” 
o Corrected misconceptions (eg: Patient thinks they will get free medications or patient thinks 
they don’t have to follow up with their doctor after this study is done”) and recheck 
understanding.  
o Filled the informed consent checklist  
o Requested signature  
o Asked if participant has any questions 
  
Materials and supplies: 
o BP cuff 
o Patient has the cuff already (EXTRA-CVD Intervention Arm participant) 
o Patient is already familiar with the device-- no need to demonstrate 
o Patient not familiar-- device taken out of the box and demonstrated 
o Living a Healthy Life Book 
o If not checked, why not? 
o Pt declined 
o Staff forgot or didn’t have to give out 
o BP log sheets 
o        QR code sheet  
  
 
 

 
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Appendix R: AAIM High clinic context form 
 
AAIM-High 
Clinic Variables Checklist 
Date: _____________________________ 
Study site (circle one): 
UH/SIU 
MetroHealth  
Duke 
 
Which of the following potential barriers to providing telemedicine care has your clinic experienced 
during the pandemic? 
 
Not a 
barrier 
 
Modest 
Barrier 
 
Significant 
Barrier 
Patient access to hardware 
(smartphone, laptop w/camera, 
etc…) 
1 
2 
3 
4 
5 
Patient tech literacy 
1 
2 
3 
4 
5 
Patient access to wireless or 
cellular data 
1 
2 
3 
4 
5 
Administrative pressure to do 
more in-person visits 
1 
2 
3 
4 
5 
Provider tech literacy 
1 
2 
3 
4 
5 
Provider discomfort or lack of 
experience providing telemedicine 
1 
2 
3 
4 
5 
Inappropriate physical 
environment to conduct virtual 
visits  
1 
2 
3 
4 
5 
 
 
 
What platforms does your health system offer for “virtual” videoconference appointment with 
patients?  Rank them in order of frequency of use (1 = most used) 
 Doxy.me  
 
Rank: ________ 
 Zoom 
 
 
Rank: ________ 
 FaceTime  
 
Rank: ________ 
 Other: ________  
Rank: ________ 
 Other: ________  
Rank: ________ 
On average across all providers, what proportion of the clinic’s total visits fell in each of the 
following categories during each of these periods of time (Each column must add to 100%): 
 
Mar - Jun 2020 Jul-Oct 2020 Nov 2020 - Feb2021 Mar 2021- Current 
In-Person 
 
 
 
 
Telephone 
 
 
 
 

 
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“Virtual” audio + visual 
 
 
 
 
 
Please describe how clinic providers have been educated about providing “virtual” care during the 
pandemic (paragraph notes): 
 
_______________________________________________________ 
 
_______________________________________________________ 
 
Please discuss the clinic culture around providing virtual care with a focus on any characteristics you 
believe might be unique to your setting: 
_________________________________________________________________________________ 
_________________________________________________________________________________ 
 
Is there anything else about your clinic setting that you believe may influence how the AAIM-High 
intervention will be implemented at your site: 
_________________________________________________________________________________ 
_________________________________________________________________________________ 
 
 
 

 
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Appendix S: Key Informant Interview Guides for PLHIV 
and Clinicians 
Key Informant Interview Guide for Patients Living with HIV 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in your thoughts and beliefs about a 
recent blood pressure and cholesterol study with [study nurse] we tested in your HIV clinic. I am 
going to ask you some questions about the intervention to hear about your experiences and 
perspectives. Please know that there is no right or wrong answer. You will notice that I won’t 
give you a lot of feedback on your responses because I don’t want to influence your answers. 
Finally, you are under no obligation to talk about anything that you are not comfortable 
discussing with me. Do you have any questions or concerns before we begin? 
Primary Questions 
Process Evaluation 
Context 
x 
What medicines do you take for your cholesterol, blood pressure, or heart? How often do you 
take them?  
x 
Prior to beginning this study, how often did you check your blood pressure at home?  How have 
you incorporated checking your blood pressure into your daily routine? 
x 
What else do you do to help prevent heart problems or lower your cholesterol or blood 
pressure? Who or what helps you do that?  
x 
Tell me about the support you have to help take care of your health, like taking your 
medications, and checking your blood pressure. Is it hard to ask for help about your health?  
x 
What makes it easier for you to take care of your health or prevent cardiovascular disease? 
What stands in the way of caring for your health? 
x 
What sort of impact does your relationship with your care team have on your health?  Tell me 
about how your relationship with providers and how it has evolved over time.  
x 
Compared to a year ago, tell me about your physical activity today.  What about what you 
typically eat? 
x 
Today, can you tell me how HIV may affect your risk for heart disease? If so, how?  
Intervention Dose and Fidelity 
x 
Did your blood pressure or cholesterol medication change during the study?  If so, tell me what 
that was like for you.   

 
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x 
You recently participated in the intervention to reduce your risk of heart disease. How, if at all, 
has participating in the intervention changed the way you think about your risk for heart 
disease? Which of your health care team members talked with you about your risk for heart 
disease over the last year? What did he or she or they say? What role, if any, did HIV have in 
those conversations?  
x 
You worked with a nurse who was supposed to help you coordinate the activities needed to 
reduce your risk of heart disease. This included calling you to remind you of your upcoming 
visits, checking in on your blood pressure monitor numbers, making sure the medications were 
working for you. Can you tell me the types of activities the nurse helped you with? [Probes: 
Which of those activities were most helpful for improving your heart health? What was it about 
that [activity] that was so helpful to you?] 
x 
How often did you interact with the nurse? [Probes: How, if at all, did phone interactions with the 
nurse differ from your in-person interactions? Which type of interaction was more common?  
Which form of communication did you prefer?] 
x 
Did the contacts with the nurse feel predictable or did you feel like you received something 
different from the nurse every time? Tell me more. 
x 
What was your experience and feelings with the number of visits and phone calls you 
participated in for this study? Explain what you believe would be the ideal number of visits and 
calls if you were going to continue engaging in an intervention like this in the HIV clinic with your 
care team. 
x 
(Enactment Fidelity) What, if anything, changed as a result of you working with the nurse? Your 
behavior (e.g. medication adherence, diet, or exercise), understanding of your health, your 
relationship with your other health care team members? Your ability to take care of your heart 
health? How? 
x 
Compared to a year ago, how do you feel about managing your blood pressure or cholesterol 
and prevention of heart disease? 
Feasibility and Acceptability 
x 
How do you feel about completing this intervention? Tell me about any thoughts you might have 
about the potential for an intervention like this to become a part of regular care for addressing 
heart health in the HIV clinic.  
x 
Was being in the intervention worth your time? Why? Would you recommend it to a friend or 
family member who also has HIV? 
x 
How did it make you feel working with the nurse? How, if at all, did your relationship or trust with 
him/her evolve over the year? 
x 
What did you like best about the intervention? What should we continue doing? 
x 
What was hard about participating in the intervention with the nurse? What would you change 
about the intervention?  

 
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Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 
x 
Can you give me an example of a time when [significant statement] happened to you   
Conclusion 
What do you want me to know that I didn’t ask you about?  (YES return to interview; NO 
proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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Key Informant Interview Guide for Clinicians 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in learning more about your thoughts and 
beliefs about a recent intervention we tested in your HIV clinic. I am going to ask you some 
questions about these topics to hear about your experiences and perspectives. Please know 
that there is no right or wrong answer. You will notice that I won’t give you a lot of feedback on 
your responses because I don’t want to influence your answers. Finally, you are under no 
obligation to talk about anything that you are not comfortable discussing with me. Do you have 
any questions or concerns before we begin? 
 
ADOPTION: Primary Questions for all Clinicians 
x 
Can you tell me how you address cardiovascular risk in your  patients living with HIV? 
x 
Does your organization [name clinic] have training or tools on helping you manage 
cardiovascular disease risk in your patients living with HIV? Please tell me about those. 
x 
Has the Nurse-led intervention changed how you talk with your patients about heart disease? If 
yes, tell me about that/those conversation(s)? Prompts: What prompted that discussion (e.g., 
did you bring it up) Did they ask you about their risk of developing heart disease?  Did their 
primary care provider reach out to you? (Implementation) 
 
ADOPTION: Intervention Dose and Fidelity 
x 
Let’s talk specifically about the intervention. As you may know, we had a nurse coordinator [ 
name nurse at the site] for CVD management for HIV+ patients at high risk for CVD. Did you 
interact with this nurse? How often did you talk to this person? What sorts of conversations did 
you have? Was everything delivered by phone or did you come in in person? Which form of 
communication did you prefer? 
x 
How did it make you feel working with this person? How did that evolve over the year?  
x 
Did the nurse coordinator interact with your patient’s primary care providers? How did that affect 
your workload? 
x 
Was having the intervention in the clinic worthwhile? Why? Would you recommend it to a 
colleague at another clinic? 
x 
(Enactment Fidelity) Did anything change as a result of you working with the nurse? Your 
behavior, understanding of your patients, your relationship with your other health care team 
members? How? 
x 
What did you like best about the intervention? What should the clinic continue doing? 
x 
What was hard about participating in the intervention with the nurse? What would you change 
about the intervention?  

 
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IMPLEMENTATION: Intervention Feasibly and Usability 
Finally, we are interested in scaling up this intervention to help other patients reduce their risk of 
heart disease. However, we know in this and many clinics, there are cultural and systemic 
issues that can make a new clinic initiative more or less successful.  We’d like to get your 
opinion on these issues and as a reminder, all information you provide will be confidential and 
aggregated across three clinics.  
System 
x 
Tell me about your clinic’s culture. What aspects of it help you do your job well and what 
aspects can make it harder for you? What are the strengths of your clinic? 
x 
What are the priorities of your clinic? Have they changed over time? 
x 
Do you think your clinic values the prevention and treatment of cardiovascular disease in 
PLHIV?  
x 
Does your clinic allocate any of its funding for the prevention and treatment of cardiovascular 
disease in PLHIV? If so, what proportion/amount would you estimate? 
x 
Does your clinic track/monitor cardiovascular process metrics (e.g., number of CVD counselling 
sessions, lifestyle referrals, or BPs checked at each encounter)? Does it track/monitor 
cardiovascular outcome metrics (e.g., number of pts with controlled BP or lipids within normal 
limits)? If so, how is that information shared with you? How does that influence your own clinical 
practice? 
x 
Is there anything that your HIV clinic currently does not have that would benefit your patients’ 
cardiovascular health (e.g., funding, more staff, etc) 
 
x 
Are there any cardiovascular health services that you currently do not offer that you would like 
to? (if yes, what is preventing you from providing these services)  
 
x 
What areas of cardiovascular health do you think future research should focus on? (e.g. 
outcomes, cost benefit, mentor training, etc) 
 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 

 
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x 
Can you give me an example of a time when [significant statement] happened to you   
 
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 

 
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Key Informant Interview Guide for Prevention Nurses 
Introduction  
[Remind about Audio Recording and not to use real names]  
Thank you for talking with us today. We are interested in learning more about your thoughts and 
beliefs about your participation in the EXTRA-CVD or AAIM-High clinical trials.  I am going to 
ask you some questions to hear about your experiences and perspectives. Please know that 
there is no right or wrong answer. You will notice that I won’t give you a lot of feedback on your 
responses because I don’t want to influence your answers. Finally, you are under no obligation 
to talk about anything that you are not comfortable discussing with me. Do you have any 
questions or concerns before we begin? 
 
ADOPTION: Intervention Dose and Fidelity 
x 
Let’s talk specifically about how the intervention was delivered at the [UH/Metro/Duke] HIV 
clinic.  Tell me first about the range of your interactions with providers at [UH/Metro/Duke]. Were 
there some providers that embraced and engaged with the intervention? Were there some that 
were less enthusiastic or even antagonistic?  What sorts of conversations did you have with 
providers? Did you interact by phone or did you come to clinic in person? Which form of 
communication did you prefer? 
x 
How did your interactions evolve over the course of the 30 month trial period? 
x 
Now tell me about your interactions with non-HIV providers.  How often did you interact with 
primary care providers or non-HIV specialist providers outside of the HIV clinic?  How were your 
interactions with these providers different than for the HIV clinic providers? 
x 
(Enactment Fidelity) Do you believe that you were able to improve the cholesterol and blood 
pressure care of participants in the intervention? What aspects of the intervention were the most 
helpful in making these improvements? Are there any other outcomes you can think of that 
improved because of participation in the intervention (i.e., what other changes did you notice in 
participants?) 
x 
What did you like best about the intervention? What should continue doing? 
x 
What was hard about being the prevention nurse for this intervention? What would you change 
about the intervention?  
 
MOTIVATIONAL INTERVIEWING 
As part of the trial, you received specific training and ongoing coaching about motivational 
interviewing (MI) techniques to help the trial participants with behavior change.  We are now 
going to ask you a few questions about your experience learning and using MI.   
x 
We wonder if MI skills are important for the success of the intervention. What are your thoughts 
on this?  Was the time and energy invested in training and coaching worth the results achieved?   

 
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x 
Are there any other outcomes (besides blood pressure and cholesterol changes) you can think 
of that improved because of participation in the intervention (i.e., what other changes did you 
notice in participants?) 
x 
Describe the impact (if any) MI skills had on your relationship with participants (e.g., trust, 
engagement, empathy, etc.). 
x 
How important do you think ongoing MI coaching and feedback would be for nurses working on 
similar interventions to improve their MI performance?  What form should that 
coaching/feedback take?  What would you keep or change about how the coaching was 
provided for this trial? 
x 
What are the benefits to using MI which may not be easily captured in the main outcome 
measures of this trial (i.e. blood pressure and cholesterol change)?   
x 
Reflecting on your use of MI with trial participants, do you think that there are trends in 
socioeconomic circumstances, demographics, behaviors, and/or health status that either help or 
deter the usefulness of MI to improve intervention outcomes? Similarly, are there underlying 
phenomena that make you feel more or less confident in successfully interacting with 
participants using the MI spirit or skills? 
x 
Overall, how (if at all) have you incorporated MI into your interactions with participants? Probes: 
Did you find that you regularly embraced the spirit of MI and used MI skills, or was it something 
you felt you did only during process evaluation recordings?  
 
IMPLEMENTATION: Intervention Feasibly and Usability 
Finally, we are interested in scaling up this intervention to help other patients reduce their risk of 
heart disease. However, we know in this and many clinics, there are cultural and systemic 
issues that can make a new clinic initiative more or less successful.  We’d like to get your 
opinion on these issues and as a reminder, all information you provide will be confidential and 
aggregated across three clinics.  
System 
x 
Tell me about the [UH/Metro/Duke] clinic’s culture. What aspects of it helped you do your job 
well and what aspects made it harder for you? What are the strengths of your clinic? 
x 
What are the priorities of your clinic? Have they changed over time? 
x 
Do you think your clinic values the prevention and treatment of cardiovascular disease in 
PLHIV? How (if at all) have these values changed since the beginning of the trial?  
x 
Does your clinic allocate any of its funding for the prevention and treatment of cardiovascular 
disease in PLHIV? If so, what proportion/amount would you estimate? 
x 
Does your clinic track/monitor cardiovascular process metrics (e.g., number of CVD counselling 
sessions, lifestyle referrals, or BPs checked at each encounter)? Does it track/monitor 
cardiovascular outcome metrics (e.g., number of pts with controlled BP or lipids within normal 
limits)? If so, how is that information shared with you? How does that influence your own clinical 
practice? 

 
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x 
Is there anything that your clinic currently does not have that would benefit your patients’ 
cardiovascular health (e.g., funding, more staff, etc) 
 
x 
Are there any services that the clinic currently does not offer that would be valuable in 
addressing cardiovascular health? (if yes, what is preventing the clinic from providing these 
services)  
 
x 
What areas of cardiovascular health do you think future research should focus on? (e.g. 
outcomes, cost benefit, mentor training, etc) 
 
Secondary/Follow-up Questions 
Follow-up “Probes” after significant statements are made:  
[Earlier/A moment ago/when you first started speaking/when you were talking about x] you said 
[significant statement].  
x 
Can you tell me more about that?  
x 
Can you tell me more about how that affects [X] 
x 
Can you clarify what you mean by [significant statement] 
x 
Can you give me an example of a time when [significant statement] happened to you   
 
Conclusion 
Is there anything else you want us to know about [X]?  (YES return to interview; NO proceed) 
We want to thank you so much for your participation and remind you that everything we have 
discussed will remain private. The audio file will be destroyed once this interview is transcribed, 
and the transcription will not contain your name or any identifying information.  
 
 
 
 

 
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Appendix T: Examining the role of context on the 
adaptability of the EXTRA-CVD intervention through 
transportability analysis, stakeholder engagement, and the 
construction of a dose composite measure 
 
Study Protocol and Manual of Procedures 
 
Lead investigator: Angela Aifah, PhD, AM; NYU Grossman School of Medicine 
Funded by: NHLBI (U01HL142099-S1; Diversity Supplement) 
Date & Version no.: 18th July 2022, version 1 
 
1. PROTOCOL SUMMARY 
 
Study Description: This study uses mixed-methods approaches and stakeholder feedback to 
develop fa composite measure of dose (i.e. the dose delivered and dose received) to explain the 
effectiveness of the EXTRA-CVD intervention of the parent study [A nurse-led intervention to 
EXtend the HIV TReatment cAscade for CardioVascular Disease prevention (EXTRA-CVD); 
(U01HL142099)].  
 
Aim: To develop a pragmatic dose composite measure (i.e., the frequency and intensity) for the 
EXTRA-CVD intervention. 
 
Objectives: Use a group concept mapping approach of stakeholder engagement and the Delphi 
method to formulate the dose composite measure.  
 
Endpoints: Dose composite measure of the parent study, EXTRA-CVD. 
 
Study population: Stakeholders, including those who have participated in previous stakeholder 
activities for the parent study (design team). These individuals include the EXTRA-CVD nurses, 
physicians, social workers, dieticians etc.  
 
Study duration: 6 months 
 
2. SCHEDULE OF ACTIVITIES (in months) 
 
Activity 
M-1 
M-2 
M-3 
M-4 
M-5 
M-6 
Finalize protocol & obtain IRB 
approval 
X 
 
 
 
 
 
Send invitations to 
participants 
X 
 
 
 
 
 
GCM steps 1 to 4 
 
X 
X 
 
 
 
GCM steps 5 & 6 
 
 
 
X 
 
 
Delphi rounds 1 to 3 
 
 
 
 
X 
 

 
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Share findings with 
stakeholders & research team 
 
 
 
 
 
X 
 
 

 
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3. BACKGROUND 
 
Within United States HIV clinics, there is limited evidence examining the effectiveness of 
implementation strategies to address the burden of comorbid HIV and atherosclerotic 
cardiovascular disease (ASCVD). Equally important to implementation effectiveness is the dose 
of an intervention – i.e. the frequency or duration of exposure to the intervention. Research from 
evidence based interventions (EBIs) underscore the importance of dose on the adoption and 
sustainability of interventions within routine practice care settings. While agreement on the link 
between dose and intervention outcomes is clear, there is less evidence in support of the 
development of optimal dose composite measures for EBIs, particularly pragmatic measures 
which include stakeholder feedback.  
Stakeholder-engaged research is an important driving force for the implementation of science-led 
behavioral interventions, particularly as it pertains to engaging stakeholders early and frequently 
throughout the implementation period. More importantly, while most approaches for stakeholder-
engaged research typically incorporate qualitative methods, robust mixed-method approaches 
such as group concept mapping (GCM) are increasingly being applied to implementation research 
for a number of reasons including developing criteria for pragmatic measures. GCM is a novel, 
participatory approach to stakeholder engagement and topic development, whereby the 
perceptions of participants on a specific subject are elicited and then used to generate illustrative 
conceptual frameworks of the target group or end-users views.  
A recent study applied a two-step approach for engaging stakeholders by using GCM and the 
Delphi method to operationalize pragmatic measures for implementation science outcomes (i.e. 
acceptability, appropriateness, and feasibility) and establish rating criteria for assessing the 
construct.  In particular, Powell et al. apply the Delphi technique as a follow-up step to better refine 
and consolidate the list of criteria generated from the GCM step. The consensus-building 
approach of Delphi uses an iterative process to collect data from key or expert stakeholders in a 
pre-specified sequence. The use of mixed-methods in stakeholder analysis such as group 
concept mapping and the Delphi technique offers unique opportunities to enhance the adoption 
of EBIs through the development of a pragmatic dose composite measure. The current study 
similarly incorporates the two-step process of GCM and Delphi to engage key stakeholders in 
developing a dose composite measure for the parent study.  
Total dose of complex multi-component interventions is often difficult to conceptualize.  For 
example, the EXTRA-CVD intervention consists of 4 primary components (nurse-led care 
coordination, home blood pressure (BP) monitoring, algorithms for evidence-based prescribing of 
BP meds, and electronic health records tools).  Each of these 4 components is further composed 
of multiple activities including telephone calls with patients, telephone calls with providers, 
prescription of new medications or uptitration of medication, home blood pressure monitoring, 
etc…)  Some of these may be more or less important in the eyes of key stakeholders who include 
patients, doctors, clinic nurses, and the EXTRA-CVD interventionist nurses.  For example, how 
does one weight the value of a 15 minute phone conversation with the patient vs. a 15 minute 
phone conversation with a prescribing doctor?  The aim of this study is to engage these 
stakeholders in the construction of an a priori composite measure of dose that is based on 
personal and clinical experience.  This measure of dose will then be used as a potential mediator 
of EXTRA-CVD outcomes, including both primary and secondary clinical outcomes (BP & 
cholesterol) but also implementation outcomes and other outcomes of interest (i.e. time to 
disengagement for those who are lost to follow-up).   

 
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4. STUDY AIM & OBJECTIVE 
 
Aim 
Objective 
To develop a composite (or hybrid) dose 
measure of the EXTRA-CVD intervention. 
Conduct 
stakeholder 
engaged 
activities 
through group concept mapping and the 
Delphi method. 
 
5. STUDY DESIGN 
 
The objective of this study will be to use a GCM approach along with the Delphi method to engage 
roughly twenty EXTRA-CVD stakeholders on constructing a pragmatic dose composite measure 
for the parent study intervention.  
 
Two-part approach: first, use group concept mapping to identify factors important for dose 
composite measure and second, use the Delphi process to develop a final dose compose 
measure.  
 
All activities for the GCM phase will be conducted online using the Concept Systems software 
and will include one full group meeting for step 5, which will be done via Zoom or WebEx. The 
Delphi process activities, i.e. questionnaires, will be conducted online.  
 
5.1  Part A: Group Concept Mapping 
 
Group Concept Mapping (GCM) is a six-step process: 1) preparation, 2) generation, 3) structuring, 
4) representation, 5) interpretation, and 6) utilization. See Figure 1 for an overview of the GCM 
steps. Below are the definitions for the six steps along with the activities that will take place at 
each step for this study. The descriptions of the steps are based on the work  and explanations 
provided by Burke et al. (2005).  
x 
Step 1, Preparation: Identify key focal topics (e.g., developing the prompt for participants 
to respond to or address) and determine participant selection criteria. For this study, the 
prompt will be “Based on your review of the data for the EXTRA-CVD dose received and 
delivered what are some factors that you think are important for putting together a dose 
measure (i.e., considering both dose received and delivered) for the intervention?” This 
prompt will be shared with participants via a link sent from the Concept Systems program. 
Participants will be asked to create an account from which they can easily complete all of 
the activities online or on the web platform.  
x 
Step 2, Generation: Participants respond to the prompt and provide a list ofresponses 
that will be used data collection and analysis. In this study, participants will be asked to 
provide up to 8 responses to the prompt question.  
x 
Step 3, Structuring: Participants independently sort and rate the complete list of 
responses or items. Participants will sort the responses or items into piles of statements 

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based on their perceived similarity. Following the sorting of the responses, participants 
then rate the responses according to its importance or usefulness to the focal question.  
x 
Step 4, Representation: Once all of the sorting-and-rating data is collected, the Concept 
Systems software will then analyze the data to provide quantitative summaries and visual 
representations of the relationship between and importance of the responses. As noted 
by Burke et al. (2005), the visual representations or concept maps are “based on a 
sequence of analyses that includes most prominently multidimensional scaling and 
hierarchical cluster analysis. All analysis will be conducted by the study investigator and 
completed using the Concept Systems software.  
x 
Step 5, Interpretation: In a group setting, participants will be asked to provide feedback 
on the concept maps – particularly to discuss the cluster domains (and individual 
responses represented in the clusters) produced from the sorting and rating activities.  
x 
Step 6, Utilization: For this final step, the findings will be discussed among the 
investigative team to determine how they best inform the original prompt.
 
 
FIGURE 1: OVERVIEW OF GCM STEPS 
Expected outcome of the GCM phase: Shortlist of factors that participants believe best 
represent an optimal dose measure for the EXTRA-CVD intervention. The data source for the 
GCM component will be based on the process evaluation measures on the dose received and 
delivered from the parent study. Following GCM, the Delphi process will incorporate the GCM-
generated list of factors to establish a consensus on the criteria for potential dosage measures 
for the intervention. The procedure for the Delphi Process is noted below.  
 
5.2  Part B: Delphi Process 
The Delphi process will include 3 rounds of questionnaires to reach a general consensus on an 
appropriate and acceptable dose measure for the parent study. Areas of consideration for the 
Delphi participants will be selecting key components for the dose composite measure as well as 
deciding how to effectively “weight” the value of the components for the measure. Throughout the 
process, participants will be asked to rate or rank-order items which they believe are most 
applicable until a consensus is reached during the final round on the key factors for a dose 
composite measure. The questionnaires will be accessible via a link that will be emailed to 
participants. Using an online link will allow for subject anonymity – an advantage of the Delphi 
technique. 
 

 
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6. STUDY POPULATION 
 
Individuals who meet the following study eligibility will be included in the stakeholder activities.  
 
Inclusion criteria 
x 
Participant in previous EXTRA-CVD or AAIM-HIGH Design Team sessions.   
x 
EXTRA-CVD or AAIM-High study personnel 
x 
Able to provide consent. 
 
Exclusion criteria 
x 
There are no exclusion criteria 
 
7. STUDY ACTIVITIES 
 
7.1  Recruitment of participants 
 
Individuals from the two geographic sites (i.e. Cleveland, Ohio and Durham, North Carolina) who 
participated in the human-centered design process of the parent study who indicated on their 
previous consent form that they would be willing to participate in future studies will be invited to 
participate in this study.  Our goal sample size is 20 total participants, with a minimum of 20 total 
participants.  If we do not reach our goal sample through invitations to design team members, 
then we will invite EXTRA-CVD or AAIM-High study personnel to participate.  The design teams 
were well-balanced in terms of representation from patients, clinic staff, clinic nurses, HIV 
specialists, non-HIV specialists (e.g. cardiologists), and primary care doctors.  We will seek to 
maintain this balance of representation for the current study.   
 
7.2  Informed consent 
 
To invite design team members to participate in this study, the study team coordinators at each 
site will send an e-mail to members who have previously consented to be contacted for future 
research.  The email will explain the purpose and procedures of the new activities and will include 
a REDCap survey link to a form that will capture the participant’s interest in participating in or 
declining the invitation to participate. For those that decline, the REDCap survey will end, thanking 
the member for their time. For those that are interested in participating, the REDCap survey will 
inform the design team member that a study team member will need to contact them to complete 
the informed consent process, and the survey will capture the preferred communication method 
to schedule that virtual visit (e-mail or phone contact information). A study team member will then 
contact the design team member through phone or e-mail to schedule the virtual informed consent 
visit and explain the process. A study team member will email a REDCap survey link to the full 
version of the consent document to the participant on the scheduled date. This virtual consent will 
capture an electronic signature and follow most of the guidelines laid out by the UH IRB in their 

 
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document titled Guidelines for Remote Electronic Consent. An exception will be the audiovisual 
visit to confirm identity, as the study team has determined that this will place unnecessary burden 
on the design team members. All design team members have worked closely with the study team 
in the past and their identity is well-known to the study team. Aligning with data previously 
captured from participants, the study team member will ask the participant for their full name, 
professional title at their respective site, and their e-mail address to confirm their identity over the 
phone, and will then perform verbal informed consent while the participant reads along through 
the REDCap survey link. The participant will then provide their electronic signature in RedCap 
confirming their consent to participate. 
 
7.3  Discontinuation/ Withdrawal of Participants from Study 
 
Each participant has the right to withdraw from the study at any time. In addition, the Investigator 
may discontinue a participant from the study at any time if the Investigator considers it necessary 
for any reason including:  
x 
Ineligibility either arising during the study period or retrospectively having been overlooked 
during recruitment or consent. 
x 
Significant protocol deviation. 
x 
Significant non-compliance with study requirements. 
x 
Withdrawal of consent. 
 
8. DATA ANALYSIS  
 
The GCM will be administered via an online link such that participants will be able to respond to 
a focus prompt, e.g. “Based on your review of the data for the EXTRA-CVD dose received and 
delivered what are some factors that you think are important for putting together a dose measure 
(i.e. considering both dose received and delivered) for the intervention?”. Once participants 
respond to the focus prompt and the collected data is organized to remove redundant or similar 
statements, they will be given the opportunity to rate and sort the statements based on pre-
established criteria. Following the rating and sorting activity, the collected data will then be 
analyzed using the online Concept Systems Global MAX software (The Concept System Global 
MAX, 2019) and based on multidimensional scaling (MDS) with a dimensional solution to arrange 
and produce cluster maps which show the thematic associations of the statements. Participants 
will then have a focus group meeting to provide feedback on the cluster maps and choose the 
cluster map of statements which they believe will best represent the key constructs or variables 
for developing a pragmatic dose composite measure for the intervention. 
 
Based on the combined results from the GCM focus groups from both sites, the Delphi technique 
will then be used to develop a final composite measure based on the questionnaire responses of 
stakeholders from 3 iterations/ rounds. During each round, the data collected from the previous 
round is consolidated and assessed by the researcher in order to develop a questionnaire that 
includes the variables or items rated highly by the participants. The outcome of this final step will 
be a composite dose measure for the parent intervention.  

 
Protocol 
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September 7, 2022 
 
 
8.1  Data Management 
 
All data from the GCM activities (including the collection of basic participant demographics) will 
be identifiable only by a participant ID number and will not contain PHI.  It will be securely housed 
on the Concept Systems Global Max software and will be password protected. The Lead 
Investigator and research assistant will be the only individuals that will have access to the GCM 
data.  
 
The Delphi activities’ data (i.e. outcomes of the 3 questionnaire or survey rounds) will be kept on 
a secure network using UH REDCap and again only linked to participant ID number. The Lead 
Investigator and research assistant will be only individuals that will have access to the Delphi 
data. 
 
9. PARTICIPANT CONFIDENTIALITY 
 
The study staff will ensure participants’ anonymity is maintained. Participants will be identified 
only by a participant ID number on all study related documents and electronic databases, with the 
exception of the in-person GCM activities (i.e. step 5), where participants can share their 
perspectives and will be addressed by their preferred name. All documents will be stored securely 
and only accessible by study staff and authorized personnel.  
 
10. EXPENSES AND BENEFITS 
 
Participants will be compensated for their time and effort on this study through $100 payments 
distributed by each site in accordance with their local policies. This payment will be provided at 
the end of all stakeholder engagement activities.  
 
 
 
 

 
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Force on Practice Guidelines. Circulation 2014;129:S49-73. 
 

1 
 
EXTRA-CVD: A nurse-led intervention to Extend the HIV Treatment Cascade for 
1 
Cardiovascular Disease Prevention 
2 
 
3 
Statistical Analysis Plan: Aim 2 
4 
 
5 
Principal Investigators: Christopher Longenecker, MD; Allison Webel, RN, PhD; Hayden Bosworth, PhD 
6 
Background 
7 
The HIV/AIDS treatment cascade model was developed to assess how people living with HIV infection 
8 
(PLHIV) access care and treatment. The model includes sequential steps in care including—(1) diagnosis, 
9 
(2) prescription of appropriate antiretroviral therapy (ART), and (3) suppression of detectable HIV virus 
10 
in the blood. These metrics are familiar to HIV-providers and integral to continuous quality improvement 
11 
initiatives at HIV specialty clinics across the United States, where most PLHIV receive care.  
12 
 
13 
PLHIV are known to have a 1.5-2x higher risk of atherosclerotic cardiovascular disease (ASCVD) 
14 
compared to uninfected individuals, a risk that persists despite viral suppression on ART. Thus, once 
15 
PLHIV achieve the final step of the HIV treatment cascade, providers have an important opportunity to 
16 
focus on preventing ASCVD and other non-AIDS comorbidities. We envision extending the treatment 
17 
cascade for high blood pressure (BP) and high cholesterol, which account for much of the population-
18 
level ASCVD risk in PLHIV4, as follows: Step 1, appropriate screening and diagnosis; Step 2, 
19 
appropriate treatment; and Step 3, achievement of guideline-based treatment targets. Currently, PLHIV 
20 
are sub-optimally treated for high BP and cholesterol, possibly due to low perceived risk for ASCVD or 
21 
challenges in primary care coordination between HIV specialists and non-HIV providers. Non-physician 
22 
led approaches may address these barriers. 
23 
  
24 
Our overarching goal is to improve the BP and cholesterol treatment cascade for PLHIV on suppressive 
25 
ART to reduce ASCVD risk. Guided by a RE-AIM framework (Reach x Efficacy—Adoption, 
26 
Implementation, Maintenance), and using a mixed-methods clinical effectiveness trial design, our 
27 
experienced multi-disciplinary team will test a contextually adapted ASCVD prevention nurse-led 
28 
intervention (EXTRA-CVD) to reach guideline-based BP and cholesterol targets. The study will be 
29 
conducted in three racially and ethnically diverse clinic contexts that are broadly representative of HIV 
30 
specialty care in the US.   
31 
Aims 
32 
Aim 1: Conduct a baseline assessment of ASCVD preventive care and perceptions of ASCVD risk in 
33 
the HIV specialty clinic environment. 
34 
Sub-Aim 1.1: Adapt the EXTRA-CVD intervention components to the HIV specialty clinic 
35 
context with key stakeholder input and data from the baseline assessments 
36 
Aim 2: Evaluate the 12-month efficacy of the EXTRA-CVD intervention to improve BP and 
37 
cholesterol control in PLHIV (Aim 2)  
38 
Aim 3: Conduct a process evaluation of the EXTRA-CVD intervention (Aim 3) 
39 
Hypothesis 
40 
We hypothesize that our prevention nurse-led intervention will lead to a clinically significant 6mmHg 
41 
reduction in systolic BP and 15mg/dL reduction in non-HDL cholesterol over 12 months compared to 
42 
those receiving general prevention education only. 
43 

2 
 
Study Design 
44 
Two-arm parallel randomized controlled clinical trial 
45 
Data Source 
46 
Primary data collection with trial participants. 
47 
• 
Vitals: 
48 
o Blood pressure: measured by RA, twice in each arm 1 minute apart. The mean of the two 
49 
right arm BP measurements will be used in analysis (systolic BP, primary outcome).  (0, 
50 
4, 8, 12 months)  
51 
o Lipid profile: non-HDL cholesterol (secondary outcome), total cholesterol, triglycerides, 
52 
HDL, LDL (exploratory outcomes); measured by lab personnel blinded to treatment arm 
53 
(0, 4, 8, 12 months) 
54 
• 
Self-report measures 
55 
o Sociodemographic characteristics 
56 
o Medical history 
57 
o Behavioral factors 
58 
• 
ASCVD risk estimator (0, 12 months) 
59 
o ASCVD lifetime risk 
60 
o 10-year risk 
61 
 
categorized as <20% 10-year risk vs. ≥20% or prior ASVCD 
62 
 
40-79 year olds only due to calculator 
63 
o Calculated by http://tools.acc.org/ASCVD-Risk-Estimator-Plus using the Pooled Cohort 
64 
o ASCVD Risk Equations (2013 ACC/AHA Guideline on the Assessment of 
65 
Cardiovascular Risk. doi: 10.1161/01.cir.0000437741.48606.98).  
66 
• 
Clinic site 
67 
Study Sample 
68 
Patients attending one of the three participating sites will be screened for eligibility. Planned enrollment is 
69 
300 participants (100 per site).  
70 
 
71 
Inclusion criteria (electronic medical record (EMR)) 
72 
• 
Age ≥18 years 
73 
• 
Confirmed HIV+ diagnosis (HIV+ ELISA with confirmatory PCR) 
74 
• 
Undetectable HIV viral load: defined as the most recent HIV viral load <200 copies/mL, checked 
75 
within the past year (assessed via chart abstraction)  
76 
• 
Hypertension: defined as systolic BP >130 mmHg on ≥ 2 occasions in the past 12 months or on 
77 
an antihypertensive medication (assessed via chart abstraction), and 
78 
• 
Hyperlipidemia: defined as a non HDL cholesterol level >130 mg/dL or on cholesterol lowering 
79 
medication 
80 
Exclusion criteria (EMR and patient report) 
81 
• 
On lipid-lowering medication solely for CVD prevention with evidence of pre-medication non-
82 
HDL which was already below National Lipid Association (NLA) target (100 mg/dL) 
83 
• 
On anti-hypertensive medications solely for a non-hypertension indication (e.g. systolic heart 
84 
failure) 
85 
• 
Severely hearing or speech impaired, or other disability that would limit participation in the 
86 
intervention components 
87 

3 
 
• 
In a nursing home and/or receiving in-patient psychiatric care 
88 
• 
Terminal illness with life expectancy < 4 months 
89 
• 
No reliable access to a telephone  
90 
• 
Pregnant, breast-feeding, or planning a pregnancy during the study period 
91 
• 
Planning to move out of the area in the next 12 months 
92 
• 
Non-English Speaking 
93 
Outcomes 
94 
• 
Primary: 12-month change in systolic BP, calculated as the mean of two systolic BP readings 
95 
measured in the right arm, 1 minute apart. 
96 
• 
Secondary: 12-month change in non-HDL cholesterol, calculated as total cholesterol – HDL. 
97 
• 
Tertiary: change in the extended cascade categories for hypertension and hypercholesterolemia  
98 
o Hypertension: 4-level category 
99 
 
Undiagnosed: hypertension is not listed on the EMR problem list 
100 
 
Appropriately diagnosed: hypertension listed on the EMR problem list 
101 
 
Appropriately managed: at least one medication prescribed for hypertension 
102 
 
At treatment goal: <130 systolic  
103 
o Hypercholesterolemia: 4-level category 
104 
 
Undiagnosed: hypercholesterolemia is not listed on the EMR problem list 
105 
 
Appropriately diagnosed: hypercholesterolemia listed on the EMR problem list 
106 
 
Appropriately managed: at least one medication prescribed for 
107 
hypercholesterolemia 
108 
 
At treatment goal, based on lifetime ASCVD risk 
109 
- 
Low-moderate risk: <130 mg/dl 
110 
- 
High: <100 mg/dl 
111 
- 
Very high: <100 mg/dl 
112 
o Measured at each time point 
113 
 
Diagnosis, management: EMR review by nurse 
114 
 
At goal: measurement at that visit 
115 
 
116 
• 
Exploratory: change in additional lipid measurements 
117 
o Total cholesterol 
118 
o Triglycerides 
119 
o HDL 
120 
o LDL 
121 
 
122 
Statistical Analysis 
123 
Descriptive analyses 
124 
Beginning with the chart review process, we will track ineligibility (number of patients, reasons), 
125 
declining to participate, and agreeing to participate but not proceeding to the initial visit. Once a patient 
126 
agrees to the phone screen, we will collect age, race, ethnicity, sex at birth, and gender. We will compare 
127 
demographics for those who enroll in the study to those who decline participation and to those who are 
128 
not eligible, using two sample t-tests (or nonparametric equivalent) and χ2 tests. (Table S1) 
129 
 
130 
We will further describe participating patients’ characteristics (sociodemographic, lifestyle, medical 
131 
history). Continuous variables will be reported using mean (SD) or median (Q1, Q3) and categorical 
132 

4 
 
variables will be reported as N (%). These statistics will be reported for the overall sample and by study 
133 
arm. (Table 1) 
134 
 
135 
Primary analyses 
136 
The primary intervention effect analyses will utilize continuous, linear mixed models (LMM) to test for 
137 
differences over time between the study arms. The general mean structure of the LMM we will use to 
138 
examine the hypotheses is:  
139 
Y_ij = β_0 + β_1*I(month=4) + β_2*I(month=8) + β_3*I(month=12) + 
140 
β_5*arm*I(month=4) + β_6*arm*I(month=8) + β_7*arm*I(month12)  + β_8*clinic2 + 
141 
β_9*clinic3 
142 
 
143 
where Y_ij represents the outcome of interest (i.e., SBP or non-HDL) for patient i at time j. In 
144 
this model, we fit a common intercept and arm is the intervention group indicator. Similarly, time is 
145 
classified, where for example, I(month=12) is a dummy variable equal to 1 for the 12 month time point. 
146 
Random intercepts will be included for each individual to account for correlation among repeated 
147 
measurements over time. The primary analytic model will adjust for clinic site as fixed effects, 
148 
represented with indicator variables clinic2 and clinic3, above. The mixed effects model parameters will 
149 
be estimated and tested using SAS PROC MIXED (SAS Institute, Cary, NC), and the hypothesis of 
150 
between-arm differences over time will be tested using estimate statements within PROC MIXED. In 
151 
particular, β_7, the estimated difference in outcome between arms at 12 months, will be the primary 
152 
effectiveness outcome assessed.  
153 
 
154 
For the tertiary outcome of cascade category, we will calculate an ordinal four-level variable at baseline, 
155 
4, 8, and 12 months. We will use a proportional odds model fit via generalized estimating equations to 
156 
examine differences over time between study arms. The proportional odds assumption will be assessed 
157 
using score tests, and the model will be relaxed to partial proportional odds if necessary. Robust sandwich 
158 
standard errors will be used to account for potential overdispersion and correlation among the repeated 
159 
observations over time. Similarly to the primary analysis, the model will adjust for clinic site and include 
160 
the same general mean model specification. The primary hypothesis will be tested via SAS PROC 
161 
GENMOD to assess whether the estimated proportions in each level at 12 months differ between arms.  
162 
 
163 
All analyses will be conducted following an intention to treat (ITT) principle using all available data. 
164 
Clinically significant changes specified a priori are a 5-point change for SBP and a 15-point change for 
165 
non-HDL cholesterol. 
166 
 
167 
Missing data 
168 
We will assess mechanisms for missing data in this study. LMM, implicitly accommodates missingness 
169 
when the response is Missing At Random (MAR); that is, when missingness is due either to treatment, to 
170 
prior outcome, or to other baseline covariates included in the LMM.  
171 
 
172 
Our primary analysis will include all available study-collected data. Those with missing SBP or non-HDL 
173 
cholesterol will remain missing for the corresponding cascade, even if EMR data is available for the first 
174 
two categories (because it would be missing for the last categories).  
175 
 
 
176 
Attrition bias 
177 
As part of our examination of missing data, we will assess differences in baseline characteristics (e.g., 
178 
clinic site, demographics, clinical values, medical history) by retention at each follow up time point. We 
179 

5 
 
will use two sample t-tests (or Wilcoxon rank sum tests) for continuous variables and χ2 tests for 
180 
categorical variables.  
181 
 
182 
Subgroup analyses and moderation 
183 
Pre-specified sub-group analyses of the primary, secondary, and tertiary outcomes will include clinic site, 
184 
sex, and baseline ASCVD risk (<20% 10-year risk vs. >20% or prior ASCVD).  For each category, we 
185 
will examine the interactions with intervention arm and time. Generally, the modeling approach will 
186 
mirror that described above for each outcome. Three separate analyses for each outcome will be 
187 
conducted to assess the effect of each potential moderator. Models will be fit in SAS PROC MIXED and 
188 
GENMOD, as described above, and the moderating effect of each of the three factors will be assessed via 
189 
the hypothesis test of the three-way interactions among subgroup, treatment, and time points (4, 8, and 12 
190 
months). As these analyses are exploratory and hypothesis generating in nature, we will not adjust the 
191 
alpha value. Interpretation will focus on trends and consistent results over time.  
192 
Given that some of the participants are treated by study investigator physicians, we will conduct an 
193 
additional subgroup analysis stratified by treating physician (EXTRA-CVD investigator or not). The 
194 
primary analysis will be repeated with this stratification variable for our primary, secondary, and tertiary 
195 
outcomes. Intervention effects will be descriptively compared by treating physician status. 
196 
Anticipated tables 
197 
Table 1. Patient characteristics (demographic, medical history, lifestyle), overall and by treatment arm 
198 
Table 2. Primary, secondary, and tertiary outcomes at each time point, by treatment arm 
199 
Table 3. Intervention effects (LMM and proportional odds models) on primary, secondary, and tertiary 
200 
outcomes 
201 
Table 4. Moderation effects: clinic site; sex; baseline ASCVD risk 
202 
Table 5. Intervention effects stratified by treating physician (EXTRA-CVD investigator or not) 
203 

6 
 
Table 1. Patient characteristics at baseline, overall and by treatment arm 
204 
Variable 
Overall 
Treatment arm 
 
 
Intervention 
Control 
N 
 
 
 
 
 
 
 
Demographic characteristics 
 
 
 
Age (years), Mean (SD) 
 
 
 
Gender 
 
 
 
Male 
 
 
 
Female 
 
 
 
Transgender Male/Transman/FTM
 
 
 
Unknown 
 
 
 
Ethnicity 
 
 
 
Hispanic/Latinx 
 
 
 
Non-Hispanic/Latinx 
 
 
 
Unknown 
 
 
 
Race 
 
 
 
African American/Black 
 
 
 
White 
 
 
 
Other race 
 
 
 
Multiracial 
 
 
 
Unknown 
 
 
 
 
 
 
 
Clinical characteristics 
 
 
 
Most recent CD4+ count 
 
 
 
Nadir CD4+ count 
 
 
 
Most recent viral load 
 
 
 
Antihypertensive medications 
 
 
 
None 
 
 
 
Thiazide diuretic 
 
 
 
ACE inhibitor 
 
 
 
Angiotension Receptor Blockers 
 
 
 
Beta Blockers 
 
 
 
Dihydropyridine CCB 
 
 
 
Non-dihydropyridine CCB 
 
 
 
Alpha-2-blocker 
 
 
 
Alpha-blocker 
 
 
 
Hydralazine 
 
 
 
Aldosterone antagonist 
 
 
 
Other 
 
 
 
Number of antihypertensive drugs, 
median (Q1, Q3) 
 
 
 
Cholesterol lowering drugs 
 
 
 
None 
 
 
 
Statin 
 
 
 
Ezetimibe 
 
 
 
Other 
 
 
 
 
 
 
 
ASCVD History 
 
 
 
Prior myocardial infarction 
 
 
 
Stroke/transient ischemic attack 
 
 
 
Other ischemic heart disease 
 
 
 
Peripheral artery disease 
 
 
 

7 
 
Variable 
Overall 
Treatment arm 
 
 
Intervention 
Control 
10-year ASCVD Risk score, 40+ 
years old and without prior history of 
events 
 
 
 
Low (<5) 
 
 
 
Borderline (5-7.4) 
 
 
 
Intermediate (7.5-19.9) 
 
 
 
High (≥20) 
 
 
 
 
 
 
 
Other medical history 
 
 
 
Diabetes 
 
 
 
Heart failure 
 
 
 
Current smoker 
 
 
 
Mental health disorder 
 
 
 
 
205 
 
206 

8 
 
Table 2. Primary, secondary, and tertiary outcomes at each time point, by treatment arm 
207 
 
Baseline 
4 months 
8 months 
12 months 
 
Intervention 
Mean (SD)a 
Control  
Mean (SD)a 
Intervention  
Mean (SD)a 
Control  
Mean (SD)a 
Intervention  
Mean (SD)a 
Control  
Mean (SD)a 
Intervention  
Mean (SD)a 
Control  
Mean (SD)a 
Primary outcome 
 
 
 
 
 
 
 
 
Systolic blood 
pressure, mm Hg 
 
 
 
 
 
 
 
 
Secondary outcome 
 
 
 
 
 
 
 
 
Non-HDL cholesterol, 
mg/dL 
 
 
 
 
 
 
 
 
Tertiary outcomes 
 
 
 
 
 
 
 
 
Hypertensionb, N (%) 
 
 
 
 
 
 
 
 
Undiagnosed 
 
 
 
 
 
 
 
 
Appropriately 
diagnosed 
 
 
 
 
 
 
 
 
Appropriately 
managed 
 
 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
 
 
Hypercholesterolemiab, 
N (%) 
 
 
 
 
 
 
 
 
Undiagnosed 
 
 
 
 
 
 
 
 
Appropriately 
diagnosed 
 
 
 
 
 
 
 
 
Appropriately 
managed 
 
 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
 
 
Exploratory outcomes 
 
 
 
 
 
 
 
 
Total cholesterol, 
mg/dL 
 
 
 
 
 
 
 
 
Triglycerides, mg/dL 
 
 
 
 
 
 
 
 
HDL, mg/dL 
 
 
 
 
 
 
 
 
LDL, mg/dL 
 
 
 
 
 
 
 
 
aUnless noted otherwise 
208 

9 
 
bCategorized into one of the four mutually exclusive categories: undiagnosed (not listed on the EMR problem list), appropriately diagnosed (listed 
209 
on the EMR problem list), appropriately managed (at least one prescribed medication for hypertension/hypercholesterolemia), or at treatment goal 
210 
(<130 systolic blood pressure for hypertension and <130 or <100 mg/dL, depending on risk score, for hypercholesterolemia) 
211 

10 
 
Table 3. Intervention effects (LMM and proportional odds models) on primary, secondary, and 
212 
tertiary outcomes 
213 
 
4 months 
8 months 
12 months 
 
 
 
 
Primary outcome 
β (95% CI) 
β (95% CI) 
β (95% CI) 
Systolic blood pressure, mm Hg 
 
 
 
Secondary outcome 
β (95% CI) 
β (95% CI) 
β (95% CI) 
Non-HDL cholesterol, mg/dL 
 
 
 
Tertiary outcomes 
 
 
 
Hypertensionb, N (%) 
 
 
 
Undiagnosed 
 
 
 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
Hypercholesterolemiab, N (%) 
 
 
 
Undiagnosed 
 
 
 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
Exploratory outcomes 
β (95% CI) 
β (95% CI) 
β (95% CI) 
Total cholesterol, mg/dL 
 
 
 
Triglycerides, mg/dL 
 
 
 
HDL, mg/dL 
 
 
 
LDL, mg/dL 
 
 
 

11 
 
Table 4. Moderation effects: clinic site; sex; baseline ASCVD risk 
214 
 
Systolic Blood Pressure 
Non-HDL cholesterol 
 
4 months 
8 months 
12 months 
4 months 
8 months 
12 months 
Continuous outcomes 
β (95% CI) 
R2 
β (95% CI)  
R2 
β (95% CI)  
R2 
β (95% CI) 
R2 
β (95% CI)  
R2 
β (95% CI)  
R2 
Clinic 
 
 
 
 
 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Clinic: Clinic 2 
 
 
 
 
 
 
Clinic: Clinic 3 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Clinic: Clinic 2 
 
 
 
 
 
 
Clinic: Clinic 3 
 
 
 
 
 
 
Intervention x Clinic 2 
 
 
 
 
 
 
Intervention x Clinic 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sex 
 
 
 
 
 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Sex: Female 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Sex: Female 
 
 
 
 
 
 
Intervention x Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline ASCVD risk 
 
 
 
 
 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
ASCVD risk: High 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
ASCVD risk: High 
 
 
 
 
 
 
Intervention x High risk 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ordinal outcomes 
Extended cascade category: systolic BP 
Extended cascade category: non-HDL 
 
4 month 
8 month 
12 month 
4 month 
8 month 
12 month 
 
OR (95% CI) 
OR (95% CI) 
OR (95% CI) 
OR (95% CI) 
OR (95% CI) 
OR (95% CI) 

12 
 
R2 
R2
R2
R2 
R2
R2
Clinic 
 
 
 
 
 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Clinic: Clinic 2 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Clinic: Clinic 3 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Clinic: Clinic 2 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Clinic: Clinic 3 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Intervention x Clinic 2 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Intervention x Clinic 3 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sex 
 
 
 
 
 
 

13 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Sex: Female 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Sex: Female 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Intervention x Female 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline ASCVD risk 
 
 
 
 
 
 
Step 1: main effects 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
ASCVD risk: High 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Step 2: interaction 
 
 
 
 
 
 
Intervention 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 

14 
 
ASCVD risk: High 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Intervention x High risk 
 
 
 
 
 
 
Diagnosed 
 
 
 
 
 
 
Managed 
 
 
 
 
 
 
At treatment goal 
 
 
 
 
 
 
Interaction terms are intervention*[moderator]*timepoint. 
215 
Reference groups: clinic 1 (clinic site), male (sex), low (ASCVD risk), and undiagnosed (extended cascade for HTN and DLD) 
216 
ASCVD status: High defined as ≥20% 10-year risk or prior ASCVD; low defined as <20% 10-year risk for ASCVD 
217 

15 
 
Table 5. Intervention effects stratified by treating physician (EXTRA-CVD investigator or not) 
218 
 
4 months 
8 months 
12 months 
Continuous outcomes 
β (95% CI) 
β (95% CI) 
β (95% CI) 
Systolic blood pressure (mmHg) 
(primary) 
 
 
 
EXTRA-CVD investigator physician 
 
 
 
Non-EXTRA-CVD physician 
 
 
 
Non-HDL cholesterol (secondary) 
 
 
 
EXTRA-CVD investigator physician 
 
 
 
Non-EXTRA-CVD physician 
 
 
 
 
 
 
 
Ordinal outcomes 
OR (95% CI) 
OR (95% CI) 
OR (95% CI) 
Extended cascade category: systolic BP 
(tertiary) 
 
 
 
EXTRA-CVD investigator physician 
 
 
 
Undiagnosed 
Ref. 
Ref. 
Ref. 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
Non-EXTRA-CVD physician 
 
 
 
Undiagnosed 
Ref. 
Ref. 
Ref. 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
Extended cascade category: non-HDL 
(tertiary) 
 
 
 
EXTRA-CVD investigator physician 
 
 
 
Undiagnosed 
Ref. 
Ref. 
Ref. 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
Non-EXTRA-CVD physician 
 
 
 
Undiagnosed 
Ref. 
Ref. 
Ref. 
Appropriately diagnosed 
 
 
 
Appropriately managed 
 
 
 
At treatment goal 
 
 
 
 
219 

16 
 
Acronyms 
220 
HIV, human immunodeficiency virus (HIV+ indicates diagnosis of HIV) 
221 
AIDS, acquired immunodeficiency syndrome 
222 
PLHIV, people living with HIV infection 
223 
ART, antiretroviral therapy 
224 
CVD, cardiovascular disease 
225 
ASCVD, atherosclerotic cardiovascular disease 
226 
BP, blood pressure 
227 
RE-AIM, Reach x Efficacy – Adoption, Implementation, Maintenance 
228 
EXTRA-CVD,  
229 
RA, research assistance 
230 
HDL, high-density lipoprotein (“good” cholesterol) 
231 
LDL, low-density lipoproteins (“bad” cholesterol) 
232 
Non-HDL, non-HDL cholesterol (calculated as total cholesterol – HDL)  
233 
ELISA, Enzyme-Linked Immunosorbent Assay (a technique used to detect antibodies or infectious agents 
234 
in a sample) 
235 
PCR, polymerase chain reaction (a technique to make many copies of a DNA segment) 
236 
NLA, National Lipid Association (provides guidelines on best lipids clinical management practices) 
237 
EMR, electronic medical record 
238 
ITT, intention to treat 
239 
MAR, missing at random 
240 
FTM, female-to-male (transgender individual) 
241 
MTF, male-to-female (transgender individual 
242 
GED, general educational development (substitute for high school diploma) 
243 
OR, odds ratio 
244 
CI, confidence interval 
245 
 
246