A Nurse-led Intervention to Extend the Veteran HIV Treatment Cascade for Cardiovascular Disease Prevention (V-EXTRA-CVD)
Phase: NA
Conditions: Cardiovascular Disease, Hypertension, Care Coordination, HIV Treatment Cascade
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
 
 
 
A nurse-led intervention to extend the Veteran HIV treatment cascade for cardiovascular disease 
prevention (V-EXTRA-CVD) 
NCT04545489 
Funding Agency:  VA HSR&D IIR 19-418 
Principal Investigator/Study Chair:  Hayden Bosworth, PhD 
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Abstract 
Provide a summary of the study (recommended length: less than 500 words). 
Background: The VA is the largest provider of HIV care in the United States. The ~31,000 Veterans with HIV 
use significantly more healthcare and have up to 2x higher risk of atherosclerotic cardiovascular disease 
(ASCVD) compared to uninfected Veterans. The HIV treatment cascade model includes care steps; once 
people obtain remission, providers should focus on preventing ASCVD. We will extend the HIV treatment 
cascade and focus on reducing ASCVD risk among people with HIV. Veterans with HIV have low perceived 
risk for ASCVD and uptake of guideline-based treatment for BP is low. 
Significance/Impact: The proposed intervention has the potential to reduce ASCVD events in this population 
by more than a quarter and meet VA strategic priorities of: 1) improve timeliness of services; 2) focus 
resources more efficiently as well as address HSR&D research priorities: 1) patient centered care, care 
management, and health promotion; 2) healthcare access; 3) aging; 4) virtual care. 
Innovation: The study is innovative: Cascade Model. By leveraging the HIV treatment cascade model, we will 
create a pathway for ASCVD risk reduction to be added into widespread quality improvement initiatives. 
Stakeholder-engaged design process. We will employ stakeholder-engaged research methods to ensure the 
intervention meets the needs of patients and healthcare providers. Multi-component intervention. While each of 
the components of our intervention have an evidence base, they have not been tested together in an HIV 
context. Telehealth. We will use VA Video Connect (VVC) to monitor CVD risk factors. 
Specific Aims: 
Aim 1: Conduct a formative evaluation to adapt intervention.  
Aim 1a: Conduct qualitative interviews with Veterans with HIV and Providers to ascertain perceptions regarding 
CVD risk reductions to inform intervention adaptation.   
Aim 1b: Adapt the intervention to the VA HIV clinic context with key stakeholder input. 
Aim 1c: Conduct a retrospective review of the nationwide cohort of Veterans with HIV to evaluate hypertension 
care in order to inform needs for the study.  
Aim 2: Evaluate the 12-month efficacy of an intervention to improve systolic blood pressure in Veterans with 
HIV. Hypothesis: We hypothesize that our intervention will result in a clinically significant 6mmHg reduction in 
SBP over 12 months compared to those receiving [enhanced education + usual care] only.  
Aim 3: Conduct an evaluation of the prevention intervention.  
Exploratory aim: If effective, we will conduct a budget impact analysis and simulate 10-year cost-effectiveness 
of the intervention. 
Methodology: We will conduct qualitative interviews with care team and Veterans to adapt the intervention in 
an iterative design process. We will then conduct a RCT to evaluate an intervention to reduce ASCVD risk. The 
study will be conducted in 4 clinics among HIV+ veterans (n=300) on suppressive ART with confirmed SBP 
>140 mmHg, stratified by clinic site and hyperlipidemia status and randomized 1:1 to intervention vs. education 
control. The intervention will involve 4 evidence-based components based on our prior studies and adapted to 
veterans with HIV: (1) 
interventionist-led care coordination, (2) interventionist-managed medication and adherence support (3) home 
BP monitoring, and (4) administered VA Video Connect (VVC). The education control will receive enhanced 
education and usual care. Primary outcome: difference in 12-month systolic BP in the intervention arm vs 
control. Secondary outcome: 12-month difference in non-HDL cholesterol. We will use a mixed-methods 
design to evaluate fidelity, dose delivered/received, reach, recruitment, and context of the intervention. 
 
 
 
 
 
 

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List of Abbreviations 
Provide a list of all abbreviations used in the protocol and their associated meanings. 
ACE 
angiotensin converting enzyme 
AMI 
Acute myocardial infarction 
ARB 
angiotensin II receptor blocker 
ART 
antiretroviral therapy 
ASCVD 
atherosclerotic cardiovascular disease 
ATP 
Adult Treatment Panel 
BMI 
body mass index 
BP 
blood pressure 
CDW 
centralized data warehouse 
CITI 
Collaborative Institutional Training Initiative 
CKD 
chronic kidney disease 
CPRS 
computerized patient record system 
DBP 
diastolic blood pressure 
DUA 
data use agreement 
eGFR 
estimated glomerular filtration rate 
EMR 
electronic medical record 
EPRP 
external peer review process 
ER 
emergency room 
GCP 
good clinical practices 
HCV 
hepatitis C virus 
HDL-C 
high density lipoprotein cholesterol 
HEDIS 
healthcare effectiveness data and information set 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HTN 
Hypertension 
ID 
Infectious Diseases 
IRB 
institutional review board 
ITT 
Intention to Treat 
JNC 
Joint National Committee 
JLV 
Joint Longitudinal Viewer 
LDL-C 
low density lipoprotein cholesterol 
LMM 
Linear mixed-effects models 
LSI 
Local Site Investigator 
MAR 
Missing at Random 
MI 
myocardial infarction 
mmHg 
millimeters Mercury 
NLA 
National Lipid Association 
NRI 
nicotine replacement therapy 
OIT 
Office of Information Technology 
ORD 
Office of Research & Development 
PC 
project coordinator 

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PC-MHI 
Primary Care - Mental Health Integration 
PCP 
Primary Care Provider 
PHI 
personal health information 
PI 
principle investigator 
PWH 
Persons with HIV 
RA 
research assistant 
RCT 
randomized control trial 
RE-AIM 
Reach x Efficacy - Adoption, Implementation, Maintenance 
SAE 
serious adverse event 
SBIRT 
Screening, Brief Intervention and Referral to Treatment 
SBP 
systolic blood pressure 
SMS 
short message service 
VAHCS 
Veterans Affairs healthcare system 
VEQ 
Veteran engagement quorum 
VetREP 
Veteran Research Engagement Panel 
VVC 
VA Video Connect 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Contents 
Protocol Title:  A nurse-led intervention to extend the Veteran HIV treatment cascade for cardiovascular 
disease prevention (V-EXTRA-CVD) ................................................................................................................. 7 
1.0 
Study Personnel...................................................................................................................................... 7 
2.0 
Introduction ............................................................................................................................................. 8 
3.0 
Objectives ............................................................................................................................................. 11 
4.0 
Resources and Personnel ..................................................................................................................... 11 
5.0 
Study Procedures ................................................................................................................................. 12 
5.1 Study Design .......................................................................................................................................... 12 
5.2 Recruitment Methods ............................................................................................................................. 22 
5.3 Informed Consent Procedures................................................................................................................ 25 
5.4 Inclusion/Exclusion Criteria .................................................................................................................... 26 
5.5 Study Evaluations .................................................................................................................................. 28 
5.6 Data Analysis ......................................................................................................................................... 30 
5.7 Withdrawal of Subjects ........................................................................................................................... 34 
6.0 
Reporting .............................................................................................................................................. 34 
7.0 
Privacy and Confidentiality .................................................................................................................... 35 
8.0 
Communication Plan ............................................................................................................................. 41 
9.0 
References ........................................................................................................................................... 43 
 

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Protocol Title:  A nurse-led intervention to extend the Veteran HIV treatment cascade 
for cardiovascular disease prevention (V-EXTRA-CVD) 
 
1.0 
Study Personnel 
There are four VA sites {Durham VAHCS, Cleveland VAHCS, Baltimore VAHCS, Atlanta VAHCS} 
where research will occur. The Durham site will start first with aim 1 with support from LSIs from 
Cleveland and Baltimore.  It is anticipated that all three sites will start aim 2 – RCT at the same time.  
Principal Investigator 
Name 
Contact Information 
Affiliations 
Hayden Bosworth, 
PhD 
Durham VA Medical Center  
508 Fulton Street (152) 
Durham NC 27705 
919-286-6936 
Hayden.Bosworth@va.gov 
Deputy Director for Center 
of Innovation (COIN) for 
Health Services Research in 
Primary Care, Durham VA 
Research Professor, 
Population Health, Duke 
University 
 
 

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Table 1: NLA treatment goals for Veterans with HIV.  
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 
Figure 1: Extended Treatment Cascade for 
2.0 
Introduction 
 
The VA is the largest provider of medical care for patients with HIV.1 Veterans with HIV are high users of VA 
healthcare and generate over 700,000 outpatient visits per year (median of 7 outpatient visits annually);2 they 
are also high users of services such as hospitalizations compared to Veterans without HIV.2 The prevalence of 
optimal cardiac health is low; Veterans with HIV have a twofold increased risk of myocardial infarctions3 and a 
1.5-2 times higher risk of ASCVD compared to uninfected Veterans independent of confounders.4-6    
The CASCADE model in HIV treatment. This model was developed to assess how people with HIV access 
care and treatment by employing sequential care steps: (1) diagnosis, (2) prescription of appropriate 
antiretroviral therapy (ART), and (3) suppression of the HIV virus. This model led to large scale projects aiming 
to achieve 90% of people with HIV knowing their status, 90% of those on ART, and 90% of those on ART 
achieving virally-suppression. 7  The cascade metrics are mandated core performance measures,8 and are a 
focus of nationwide HIV quality improvement initiatives. However, ASCVD prevention and treatment are 
currently absent in the HIV cascade model.    
Why extend the treatment cascade for ASCVD prevention? For those who have achieved durable viral 
suppression (90% nationally), the focus of 
care should include prevention of ASCVD.  
Although HIV-specific factors play a role, 
traditional risk factors account for the vast 
majority of risk on a population level. Among 
the top risk factor for people with HIV with 
the greatest population level impact on 
myocardial infarction risk is hypertension, 
with population attributable risks far 
exceeding low CD4+ T-cell count or elevated 
viral load.9 Unfortunately, uptake of 
guideline-based therapies for BP is low 
among people with HIV.10-12   
 
We will extend the HIV treatment cascade to improve uptake of guideline-based ASCVD prevention 
therapies. Step 1, people with HIV should have their BP and lipids screened; abnormal values should be 
appropriately diagnosed as hypertension as well as hyperlipidemia; Step 2, those with hypertension or 
hyperlipidemia should be prescribed guideline-based therapies; and Step 3, BP and lipid measurements 
should achieve guideline-based treatment targets; this is the focus of the study.13 (Figure 1).   
Complications of HIV infection. HIV causes chronic inflammation and immune activation, which is associated 
with diabetes and CVD. Long-term inflammation 
may elevate cholesterol levels, which can harm 
blood vessels and the heart. Some antiretrovirals 
have contributed to the development of insulin 
resistance leading to diabetes. HIV and the 
treatment can also impact the brain; more than half 
of people living with HIV may experience difficulties 
with motor skills and memory – all factors that may 
contribute to increased lifestyle and medication non-
adherence.  
Blood pressure and cholesterol targets matter. 
No HIV-specific BP guidelines exist; however, 
guidelines suggest treating to a target SBP of 
140mmHg for most patients is appropriate, while 
acknowledging that certain groups may merit more aggressive targets (e.g. <130 systolic for diabetes).14,15 To 
achieve these targets, many will require more than one drug and titrating medication. Improving self-
management is thus a critical component to successful treatment of blood pressure over time.16  
For cholesterol management, HIV-specific guidelines exist;17,18 although, the National Lipid Association 
(NLA) recommendations18 are the only current guidelines from the modern ART treatment era. In 2015, the 

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NLA Expert Panel on HIV recommended an approach to risk stratification and target non-HDL-C and LDL-C 
goals19 (Table 1), with the additional recommendation that HIV infection may be counted as a major ASCVD 
risk factor for the purposes of risk stratification.  
The HIV workforce is changing.  Achieving ASCVD prevention targets is challenging with increased clinical 
demands and a changing HIV workforce. Over the past 10 years, the HIV Medicine Association 20 and the 
Institute of Medicine21 have been warning of shortages of HIV specialists; numbers of HIV providers 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 care.22 Primary care providers may be able to fill the gap, but feel 
inadequately trained in HIV care.23 Similarly, HIV-specialists are often uncomfortable providing primary care, 
including treatment for hypertension and hyperlipidemia.24 Treating higher volumes of HIV patients is 
associated with more appropriate HIV management and lower overall mortality,25 but is not associated with 
more appropriate cholesterol treatment for ASCVD prevention.26  
Models that promote shared responsibilities between primary care providers and HIV-specialists exist, 
but their effect on primary care and non-AIDS outcomes such as ASCVD has not been rigorously studied.27  
Changing patterns of care require shifts in patient-provider trust and communication.  Because of longstanding 
relationships, many HIV patients including those in the VA, trust their HIV provider for comprehensive care.24,28  
In one study, 84% of patients preferred having their HIV provider be their PCP.24 However, among 1300 
persons living with HIV who had anti-hypertensive and lipid-lowering medications prescribed primarily by ID 
specialty clinics were less likely to meet evidence-based goals for hypertension and hyperlipidemia, 
respectively; rates of BP control were less than 30%.29 The impact of patient-provider trust and communication 
networks on ASCVD prevention efforts needs to be formally evaluated among people with HIV.   
Nurse-led interventions are highly effective in high-risk individuals. The clinical role of non-physician 
providers is expanding in the VA, including HIV-specialist care providers in multi-disciplinary clinics.22,30  HIV 
care provided by these non-physician specialists is comparable to physician specialists,31 but the quality and 
comfort level of preventive care for ASCVD among these non-physicians is poorly understood.  Our 
experiences suggests that nurse-led management of cardiovascular risk factors is highly effective.32-35  
Key features of our prior interventions include: (1) care coordination, (2) interventionist-managed 
protocols and medication adherence counseling, (3) home blood pressure monitoring; and (4) integrated use of 
information technology tools such as video conferencing. For example, among a sample of Veterans with 
poorly controlled BP, home BP monitoring + behavioral counseling led to a 6mmhg reduction in systolic BP 
over 18 months in one of our prior studies.35  Further, a meta-analysis of nurse-managed protocols showed a 
clinically significant 4mmHg reduction in systolic BP and 10-12 mg/dL reduction in cholesterol.36   
Low perceived risk is a barrier to ASCVD preventive care.  Before effective antiretroviral therapy, most 
people with HIV infection died of AIDS-related causes and CVD prevention was not a priority for most patients 
and providers. Yet, there is evidence that low perceived cardiovascular risk persists even in the ART treatment 
era.37 The influence of perceived risk on ASCVD prevention behaviors are not well known. 
Unknown barriers to, and facilitators, of high-quality ASCVD preventive care in the VA. Veterans with 
HIV and their health care team experience a number of barriers to high quality ASCVD preventive care 
including a historic primary focus on HIV-related issues (e.g., CD4 T-cell counts) and competing priorities (e.g., 
substance use, poverty, psychiatric disease, pain management).  We have previously found that 135 people 
with HIV from various sites reported that during their health care visits, HIV was their primary health focus (i.e., 
HIV medications and labs).38 In the same study, health care providers reported that it can be challenging to 
cover non-HIV related preventative care issues due to 
short visit times and other priorities.38 Facilitators of 
prevention behavior included the trust that people with 
HIV have in their HIV providers and their ability to 
facilitate their decision-making and behavior.38 While 
these data reveal some of the barriers and facilitators to 
improved care for non-AIDS co-morbidities, they are 
limited by not being specific to Veterans. Additional work 
focusing on the barriers and facilitators to ASCVD care 
among Veterans will yield critical and novel data that can 
help to inform how to best tailor and implement our 
ASCVD intervention.  
Virtual Care in VA.  The VA is rolling out two virtual 
modalities to help address patient access issues as well 
The VA Video Connect (VVC) application provides 
encrypted and secure videoconference services to 
connect Veterans with their VA providers using any 
web-based or mobile device (e.g., iPhone, iPad). 
Benefits of VVC: 
• Reduction in travel time for Veterans with limited 
access to VA health care facilities (e.g., living in 
very rural areas, have medical complexity). 
• Provides quick and easy health care access. 
• For vulnerable populations using encrypted video 
ensures the session is secure and private. 
Figure 2: VA Video Connect 

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as respond to the legislative priorities such as the Choice Act and Mission Act. Two of these virtual modalities 
are critical for the delivery of population-level care management. The Office of Connected Care began rolling 
out ANNIE SMS in 2016. ANNIE SMS can incorporate two-way communication between patients and the 
interventionist and works with a smart phone, computer or mobile device connected to the Internet. 39 We will 
use this technology to collect the daily home blood pressure values. We will use video virtual care visits using 
VA Video Connect (VVC) to deliver the intervention (Figure 2). VVC can reduce the impact of barriers on 
healthcare access (e.g., distance to medical facilities), improve clinical outcomes, and is feasible and 
acceptable for Veterans with multi-morbidity and high healthcare utilization.40 Blood pressures remotely 
monitored by a clinician through video conferences may be included in the CPRS vital signs package. 
Additionally, revision to the External Peer Review Process (EPRP) data collection instrument includes 
language that telehealth BPs are acceptable. Thus, we will be able to collect BP data that will directly impact 
the HEDIS measures of the facilities we interact with during the intervention.  
PRELIMINARY DATA. Data demonstrating the importance of the project, prior experience with CVD risk 
reduction and implementation are presented.  
SITES AND POPULATION DATA.  The South accounted for half of U.S. HIV diagnoses in 2017.  Minorities 
represent the majority of new HIV diagnoses, living with HIV, and deaths among people with HIV.  Blacks have 
the highest age-adjusted death rate due to HIV disease throughout most of the epidemic. 41 We chose the 
following sites in order to provide a diverse mix of rural and urban locations.  The four sites for this project 
include the Durham VA Heathcare system, Cleveland VA Medical Center, Baltimore VA Medical Center, and 
the Atlanta VA Medical Center 
Risk and Perceptions of ASCVD risk among persons with HIV. Dr. Naggie using risk criteria delineated by 
the Adult Treatment Panel III (ATP-III) guidelines observed that 50.6% of Veterans with HIV and 33.8% of 
veterans with both HIV and HCV had an indication for statin therapy. However, among those meeting guideline 
indications, 22.7% and 31.5%, respectively, were not receiving ATP-III recommended statin therapy.10 These 
results further support that veterans with HIV are not receiving adequate ASCVD care.  
We observed that compared to other high-risk populations, people living with HIV report low perceived 
CVD susceptibility and fewer benefits from CVD prevention behaviors. Among data collected from 12 HIV 
healthcare providers and 18 individuals living with HIV, we observed that low perceived benefit to ASCVD 
prevention practices for people with HIV. Healthcare providers are more likely to identify barriers to ASCVD 
prevention/management than people with HIV.  
Prior CVD-related interventions. 1) In a Medicaid implementation project among 583 Medicaid patients 
with diabetes, we observed that a telephone self-management intervention focused on medication adherence 
improved refill rates for CVD medications from 55% to 77%.42 2) Among 641 individuals with high CVD risk in 
42 UK general practices, significant improvements CVD risk, BMI, SBP, DBP, increased BP medication 
adherence, improved diet, and increased physical activity were observed.  A cohort simulation model indicated 
the intervention was cost effective.43 3) In ACDC, Veterans with poor diabetes control were randomized to 
telemonitoring and self-management support or usual care. Those in the intervention reduced HbA1c by 1.0%, 
SBP (-7.7 mmHg) and DBP (-5.6 mmHg) versus usual care.44 
Interventions using Team-care to Improve Hypertension. V-STITCH (Bosworth, VA HSR&D IIR 20-034) 
tested a nurse-administered telephone intervention.  BP control increased from 44% to 65% in the intervention 
group compared to 44% to 53% in the control group (p=0.03) over 24 months.45 In the HINTS study (Bosworth, 
VA HSR&D IIR 04-426), 593 Veterans with hypertension were randomized; the medication management arm 
had decisions concerning their hypertension regimen made by a study physician and implemented by a nurse 
using a hypertension decision support system. Systolic BP improved in the combined group by 15.7 mmHg at 
12 months relative to usual care.33  
Multiple Risk Factors Projects. Cardiovascular Intervention Improvement Telemedicine Study (CITIES) 
(Bosworth, IIR 08-297) enrolled 429 at high risk for CVD. The intervention focused on both vascular disease-
related behaviors and medication management and was administered via the telephone. The complier average 
causal effect estimates at 6 months for intervention as compared to usual care were 20-point improvement in 
total cholesterol and 5-point improvement in Framingham risk score. 46  
Implementation Experience. The HTN-IMPROVE study (Bosworth, QUERI RRP 09-196) assessed the 
implementation of an evidence-based telephone-administered behavioral intervention to control BP in VA 
primary care clinics. 47 The project was conducted in 3 diverse VAs and 800 individuals were enrolled into the 
program. Dr. Bosworth also participated in a CMS funded diabetes demonstration project (SEDI) that involved 
public health workers in four states implementing a telephone based intervention that reduced HbA1c by 1%. 

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Experiences obtained from these implementation studies provide information on the barriers and facilitators for 
successful implementation and sustainability.  
 
Significance Summary: These data support the proposed approach and intervention; however, little work has 
investigated how to reduce CVD among Veterans with HIV. The gap between guideline-recommended CVD 
care and current practice among Veterans with HIV is a public health problem for the VA given Veterans’ with 
HIV significantly increased CVD outcomes and healthcare use. If successful, V-EXTRA-CVD could become a 
model for optimal CVD risk management and improve quality of care.   
3.0 
Objectives 
 
Our goal is to improve blood pressure (BP) treatment for Veterans with HIV to reduce ASCVD risk. Within a 
randomized clinical trial, we will test a VA adapted intervention to reach ASCVD guideline targets. The 
study will be conducted in three VA clinics that are representative of HIV specialty care in the VA.   
Aim 1: Conduct a formative evaluation to adapt intervention.  
Aim 1a: Conduct qualitative interviews with Veterans with HIV and Providers to ascertain 
perceptions regarding CVD risk reductions to inform intervention adaptation.  Care team members 
and patients will participate in qualitative interviews to understand CVD risk associated with living with HIV. 
Aim 1b: Adapt the intervention to the VA HIV clinic context with key stakeholder input.  Care team 
and patients will participate in an iterative design process to adapt our intervention to the local Veteran 
context.  
Aim 1c: Conduct a retrospective review of the nationwide cohort of Veterans with HIV to evaluate 
gaps in hypertension care in order to inform intervention needs. We will use data from the Corporate 
Data Warehouse to define hypertension care cascade among veterans with HIV who receive care at the 
VA.  
Aim 2: Evaluate the 12-month efficacy of an intervention to improve systolic blood pressure in 
Veterans with HIV.  HIV+ veterans (n=300) on suppressive ART with poor hypertension control (confirmed 
SBP >140 mmHg) will be stratified by clinic site and hyperlipidemia status and randomized 1:1 to 
intervention vs. education control. The intervention will consist of four evidence-based components derived 
from our prior studies that will be adapted to veterans with HIV: (1) interventionist-led care coordination, (2) 
interventionist-managed medication protocols and adherence support (3) home BP monitoring, and (4) 
electronic medical records (EMR) support tools. The intervention will be administered using VA Video 
Connect (VVC). The education control will receive enhanced education plus usual care from their providers 
and CVD prevention education material.   
Primary outcome: difference in 12-month systolic BP in the intervention arm vs education control. 
Secondary outcome: 12-month difference in non-HDL cholesterol.    
Hypothesis: We hypothesize that our intervention will result in a clinically significant 6mmHg reduction in 
systolic blood pressure over 12 months compared to those receiving enhanced education + usual care 
only.   
Aim 3: Conduct a process evaluation of the prevention intervention.  We will use a mixed-methods 
design to evaluate fidelity, dose delivered/received, reach, recruitment, and context of the intervention, 
corresponding to the RE-AIM domains.   
Exploratory aim: If effective, we will conduct a budget impact analysis and simulate 10-year cost-
effectiveness of the intervention. 
 
4.0 
Resources and Personnel 
 
There are four VA sites where research will occur: Durham VAHCS, Cleveland VAHCS, Baltimore VAHCS, 
Atlanta VAHCS.  

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Durham VAMC staff will recruit, enroll, and consent patients for all aims and house the research data. Statistical 
analyses will also occur at Durham 
 
Cleveland VAMC staff will also recruit, enroll and consent patients and house research data.  
 
Baltimore VAMC staff will also recruit, enroll and consent patients, and house research data.   
   
Atlanta VAMC staff will also recruit, enroll and consent patients, and house research data. Study Procedures 
 
5.1 Study Design 
Setting: The proposed study will be conducted at four VA hospitals that provide HIV specialty care for racially, 
ethnically, and age diverse Veterans with HIV.  
 
Conceptual Framework: Our study utilizes the RE-AIM framework to evaluate the intervention;48 RE-AIM 
stands for Reach X Efficacy—Adoption, Implementation, Maintenance, and captures the five factors that 
contribute to the impact of an intervention. If proven effective for ASCVD risk factor control, the concept of a 
prevention interventionist may be scaled to address a broad range of preventive care services for people with 
HIV, thus increasing its population impact. Finally, the intervention is grounded in two models of behavior 
change: (1) the information-motivation-behavioral skills model and (2) self-regulatory theory.49 These models 
explain how health behavior change is mediated through self-monitoring (lifestyle change and medication 
adherence) and acknowledge the central role that self-efficacy plays in sustained behavior change.50 (see 
Figure 3). 
 
Part 1: Aim 1: Conduct a formative evaluation to adapt intervention. 
Aim 1a: Conduct qualitative interviews with Veterans with HIV and Providers to ascertain perceptions 
regarding CVD risk reductions to inform intervention adaptation.  Care team members and patients will 
participate in interviews to understand risk associated with living with HIV and CVD and trust development in 
care provision to modify existing intervention approach. See Appendix 2 for example interview questions 
informed by the theoretical framework of this study. Final interview guides will be developed collaboratively 
with VetREP and VEQ.   

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Participants: There are two groups of participants for aim 1 
• 
Healthcare providers (both ID and primary care): up to 18 health care providers  (n=6 
providers from each site, a mix of provider type (MD, RN, NP, PA, PharmD)   will participate  
• 
Veterans with HIV: up to 18 Veterans (n=6 from each site) will participate 
These participants (veterans and providers) will complete an informant interview with Dr. Gierisch. 
Veterans with HIV will be recruited by purposive sampling and provider with purposive and snowball 
sampling. We will first interview providers to seek their guidance on key factors on which to select 
our Veteran informants.  
 
Key Informant Interviews (ID and PCP HIV Providers). We will conduct key informant interviews using a 
semi-structured interview guide focused on key elements of intervention adaptation consisting of open-ended 
questions to understand the perceptions of the clinic staff on their patients’ ASCVD risk and barriers and 
facilitators to change, how those perceptions influence how they treat CVD risk factors, thoughts on the 
intervention approach, and ideas on how to adapt the intervention to the HIV clinic context.51 We will also use 
these interviews to understand the various providers’ knowledge and concern about ART medications and 
potential interactions. The guide will facilitate discussions across sites and ensure we have covered all relevant 
topics. These interviews will occur via phone to increase access by the staff member, and audio recordings 
who will later be transcribed verbatim.  
Interview Procedures (Patients). We will interview Veterans with HIV about their perceptions of CVD risks, 
HIV medications, CVD risk reduction measures, and thoughts and adaptations needed to the intervention 
platform to make it more meaningful, feasible and acceptable for patients like them. To inform adaptation, we 
will assess barriers to, and facilitators of, improved ASCVD prevention. All interviews will take approximately 
30-60 minutes and audio recordings will be transcribed verbatim. All participating Veterans with HIV will 
complete the following assessments self-reported survey consisting of demographics, HIV and medical history, 
and perceptions of CVD Risk (Health Beliefs for Cardiovascular Disease Scale52). Medical chart abstraction will 
be used to determine history of use, adherence to, and tolerance of proven CVD prevention therapies. 
 
 
Aim 1b: Adapt the intervention to the VA HIV clinic context with key stakeholder input.  We will use a 
participatory, iterative design process53-55 including members such as: HIV providers, primary care providers, 
nurses, pharmacists, Veterans with HIV. We will consent all non-research staff members of the design teams 
verbally, and send them a welcome letter/email that includes meeting dates and details.  
The design process will involve a series of up to 4 meetings over approximately 2-3 months, for about 3-4 
hours each, with a goal of refining the V-EXTRA-CVD intervention within the VA environment. Design teams 
from each of the 3 sites will meet together, as well as breakout to discuss site-specific issues separately.  
Meetings will be conducted virtually, using approved VA technologies, such as Cisco Webex Meetings, VA 
email and MyHealtheVet secure messaging.  
The first 3 design meetings will cover the following phases: brainstorming, conceptualization, and creation.  
1. During brainstorming, the team will review the data obtained during the qualitative interviews on 
perceptions of ASCVD risk and barriers and facilitators of ASCVD preventive care. The team will 
brainstorm ideas to refine the intervention in response to these data.  
Targets for intervention adaptation include: (a) adjusting when, where, and to whom the CPRS alerts 
appear; (b) adapting the treatment algorithms to overcome barriers and maximize the facilitators; (c) targeting 
the staff training to include use of virtual care, care coordination and adherence support; (d) developing and 
tailoring staff training to facilitate acceptance, uptake, and effectiveness; and (e) helping to quickly identify and 
troubleshoot any problems with the implementation of the intervention. 
2. In the conceptualization phase, the team will evaluate advantages and disadvantages of ideas 
generated during the brainstorming and will develop concrete changes to the intervention.  
3. The creation phase will involve the refinement of treatment protocols, manuals of procedures, and 
educational materials. Once the adaptation of the intervention is completed, we will conduct 
interviews with Veterans (up to n=12)  with HIV and intervention staff from each of the three sites 
(up to n=9) to assess acceptability.56 We may also present the adapted intervention to our 
established VEQ group for further input.   

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The fourth and final design meeting (revision phase) will review information from the acceptability interviews, 
make any final recommendations to the intervention, and discuss team members’ experience of the overall 
design process.  
Aim 1c: Conduct a retrospective review of the nationwide cohort of Veterans with HIV to evaluate gaps 
in hypertension care in order to inform intervention needs.  
Persons with HIV (PWH) are at an increased risk of cardiovascular disease. Pre-hypertension and 
hypertension are both associated with an increased risk of acute myocardial infarction (AMI) in Veterans with 
HIV3 . While HTN adversely affects outcomes in PWH, HIV itself has negative impact on HTN management. 
Persistent HIV infection is a risk factor for hypertension among PWH57 ). Integration of hypertension care into 
HIV care programs has shown to produce improved outcomes when compared with traditional models of HIV 
care58. HIV primary care guidelines issued by the Infectious Diseases Society of America and the VA both 
recommend screening, prevention and control of HTN in PWH 59,60. However, to what extent are HTN services 
integrated into care of PWH and how HIV care impacts HTN care, is unknown. With over 31,000 in care, VA is 
the single largest provider of HIV care nationally and has an integrated nationwide electronic medical record. 
As such this presents a unique opportunity to investigate the relationship between HIV and HTN care. We will 
seek to compare the care cascades for HTN and HIV within this nationwide cohort of Veterans with HIV. While 
the HIV care cascade is a well-documented and widely used tool, the HTN care cascade will provide valuable 
framework for evaluating the quality of health service delivery for HTN by charting the proportion of persons 
who proceed through the stages along a defined sequence of care. Any gaps identified will define the scope of 
the problem and help inform future strategies for improving HTN care in this population. Comparing the HTN 
cascade to the HIV care cascade may function to demonstrate gaps and strengths of each program and their 
impact on each other.  
Design: 
We will collect data from the CDW files using VA provided software through VINCI using national data. The 
study population is the cohort of Veterans with an HIV diagnosis as defined using a validated definition. We will 
use demographic, ICD codes and laboratory data available in the CDW for data definitions. We will evaluate a 
5 year period from January 2015 through December 2019, but will also review data from 2020 to see how the 
COVID-19 pandemic impacted care. We will define each step in the HIV care cascade based on widely 
accepted definitions. For the HIV care cascade, we will use publicly available data provided by the VA Office of 
Specialty Care and  HIV Hepatitis and Related Conditions Office. Within this cohort of Veterans with HIV, we 
will then define corresponding, clinically relevant cascade steps for HTN based on the American Society of 
Hypertension and International Society of Hypertension clinical practice guidelines: screening, diagnosis, 
initiation of treatment, retention, control of HTN.   
 
Part 2: Intervention and Process Evaluation 
Aim 2: Evaluate the 12-month efficacy of a intervention to improve systolic blood pressure in Veterans 
with HIV.   
We will conduct an RCT of our intervention vs. education control among HIV Veterans on suppressive ART 
who have hypertension. Education control participants will receive general prevention education. The primary 
outcome is change in systolic BP and the secondary outcome will be change in non-HDL cholesterol. As 
participants conclude participation in the RCT the Aim 3 Process Evaluation will be conducted with select 
intervention participants. Relevant information from aim 2 for the process evaluation is highlighted in yellow.  
 
Setting: This trial will be conducted at the same sites described earlier: Durham VA, Baltimore VA, Cleveland 
VA, and Atlanta VA 
 
Participants: We will enroll 300 HIV+ Veterans on suppressive ART and poor hypertension control (n=25-125 
at each site). Inclusion and exclusion criteria is listed in section 5.4.    We will include individuals who have 
hyperlipidemia, defined as non-HDL > National Lipid Association (NLA) target or on lipid-lowering medication 
based on the last 3 years.  While 300 is our enrollment goal, we may consent and randomize up to 310, to 
account for site differences, withdrawals and the scheduling availability and preferences of Veteran 
participants. 
 

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Baseline visit: Participants will attend an in-person visit during which the informed process will be completed 
(see section 5.3 for informed consent procedures).  Once the veteran has provided consent and enrolled in the 
study, the baseline visit will also consist of: 
• 
Have in-office BP obtained by a trained research assistant using a standardized protocol35.  If blood 
pressure is identified by study staff as being high (>180/110), similar to prior trials, 18,45,46 we will provide 
feedback to both the patient and his/her primary care provider. In terms of the Veterans’ provider, we 
will use a developed CPRS template (requiring co-signature) and/or phone calls to notify them. If no 
action is taken, the study physician at each respective site will follow up with the patients’ provider. 
• 
Measurement of vitals: height, weight, waist circumference 
• 
Have blood drawn at VA lab to measure lipid panel. If lipid panel has been completed in the past 28 
days, will not need to repeat during baseline visit. 
• 
Complete health-related surveys (see full list of measures in section 5.5). Surveys may also be 
administered by telephone or by mail if Veteran is unable to complete the research visit in-person, but 
priority will be given to in-person survey administration. 
• 
Randomization to study arm 
• 
Assess whether Veteran has a VA-issued BP monitor for home use; if not, will have study physician 
place order. This is standard of care for all veterans with hypertension. 
 
Subsequent visits: (4,8,12 months)  
• 
Have in-office BP obtained by a trained research assistant using a standardized protocol mentioned 
above.l35 
• 
Complete health-related surveys (see full list of measures in section 5.5). Surveys may also be 
administered by telephone or by mail if Veteran is unable to complete the research visit in-person, but 
priority will be given to in-person survey administration. 
• 
Measurement of vitals: weight, waist circumference 
• 
Have blood drawn at VA lab to measure lipid panel. If lipid panel has been completed in the past 28 
days, will not need to repeat during follow-up visit. 
 
Randomization: Study statisticians will develop a 1:1 blocked randomization scheme, stratified by site and 
hyperlipidemia status. The project coordinator and research assistant will be blinded to the randomization 
schema and will randomize each subject using an automated randomization methods embedded in the study 
tracking software.  Participants will be randomized to one of two groups: 
• 
Education control group 
• 
Intervention 
 
Education control group: Participants assigned to the education group at baseline will receive usual care 
enhanced with general prevention education delivered by the research assistant in person at lab collection 
times (0, 4, 8, and 12 months). Providers will not be able to see research outcome assessment of BPs since 
these are not placed into CPRS.  
We believe it would be unethical to use a usual care comparison group. The Education control group is 
receiving more than usual care:  education material given at each visit, BP monitored and documented in 
CPRS, and providers notified if BP exceeds safety thresholds, requiring their co-signature.  
 
Intervention: Participants assigned to the intervention will also complete in-person visits every 4 months, as 
listed above but will also have additional contact with our interventionist who may be either a nurse or 
pharmacist. The in-person visits will be identical to those in the education control group, but without the in-
person education material. At their baseline visit, individuals enrolled in the intervention will be invited to 
consent and enroll in the VA Annie program, allowing them to submit home BP readings via text message 
before their intervention contacts. This is an existing VA program, but will not be required to participate in the 
intervention. 
 

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Intervention contacts:   Participants randomized to the intervention will receive a video call from the 
interventionist within 2-5 days of enrollment. While connected via video (using VVC) with the Veteran, the 
interventionist will conduct a medication assessment, including participant’s knowledge of the purpose and side 
effects of each BP or cholesterol medication and current or potential adherence strategies. If the Veteran or 
Interventionist is unable or unwilling to use VVC, these contacts may also be conducted by telephone. 
Telephone calls may be recorded for quality control purpose only (no name will be captured on the recording, 
and consent would be obtained prior to any recording). At a minimum, the interventionist will have contacts at 
0, 2, 4, 6, 8, 10 and 12 months(see figure 4). An initial 2-week follow-up call will ensure proper use of the home 
BP monitor and to 
address any other 
questions. Prior to 
each  
interventionist contact, 
similar to prior 
studies,34,61 we will 
request home BP 
values for the past two 
weeks using ANNIE 
SMS, with the goal of 
using the average of 
at least 3 values to 
determine BP control. 
For veterans 
unable/unwilling to use 
Annie, we can collect 
the home BP 
measurements over 
the phone or by secure messaging to the interventionist.  In addition, the interventionist will 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 by whether the participant remains above goal BP or is initiating new 
treatments (e.g. starting another BP medication). Regardless of contact, study outcomes are collected routinely 
at the same frequency for both arms.  
 
 
Intervention components:  
1.  Lifestyle Intervention. The interventionist will deliver a tailored behavioral, telemedicine intervention to 
improve lifestyle risks. Patients may receive up to 5 modules , based on their interest, motivation, barriers and 
stages of readiness to change. The lifestyle topics available for counseling include: tobacco cessation, 
exercise/inactivity, diet, weight, stress, sleep and alcohol misuse. The interventionist will provide resources 
related to these behaviors and when appropriate, refer individuals for follow-up care with Primary Care-Mental 
Health Integration (PC-MHI) or direct referrals to MOVE!, nutrition or smoking clinic, based on the resources 
available at each VA site. 
 
2. Care coordination. Beginning with initial enrollment, the interventionist will coordinate BP and lipid 
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 lipid 
management. The interventionist will direct management decisions to the designated provider but will facilitate 
communication by notifying the non-designated of any changes to medications.   
 
3. Interventionist-managed medication protocols and adherence support.  Participants with BP and non-
HDL not meeting CVD 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 medications.62 By using HIV-appropriate algorithms to guide 
medication titration, the prevention interventionist 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 
Figure 4: 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 outcome assessment time points, Triangles represent Virtual 
visits and lines are telephone contact.  

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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 contact where average weekly BP based on a minimum of three values exceeds 140/90mmHg, 
the interventionist will review the medication list with the patient, including any potential side-effects of each 
medication.63 The interventionist will provide counseling in several areas, including ways to enhance 
medication adherence and ameliorate side effects [as well as discuss risk factors such as physical inactivity, 
tobacco and alcohol misuse].64,65  Patients may receive a personalized medication schedule (via secure link or 
paper) that shows when they 
should take their medications, if 
requested.  
The interventionist will 
use a previously tested algorithm 
to decide on appropriate 
recommendations for medication 
changes and will approach the 
designated responsible provider 
for prescriptions and lab orders. 
34,61 Any communication in CPRS 
between the intervention 
interventionist and provider will 
require a co-signature. The 
responsible provider (not a 
member of the study team, but 
the patient’s provider who has 
been managing their hypertension, likely the PCP) will also have the option of taking the individuals OFF 
medication 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 intervention.  
Each site will have a clinical site leader who is an ID doctor familiar with current CVD/HIV treatments to 
reduce any potential drug-drug interactions.  Our ID specialists will provide input on antihypertensive choice 
before initiation, although the patient’s responsible provider is 
intended to be the one managing and prescribing these 
medications throughout the study. 
Blood pressure. We will use an evidence-based blood 
pressure treatment algorithm (Figure 6) used in our prior studies, 
in addition to the current VA/DoD Hypertension Clinical Practice 
Guidelines.66,67 A follow-up 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. Actions 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. 
Lipids. We will use an algorithm (Figure 7) adapted from 
National Lipid Association (NLA) guidelines for HIV-infected 
patients.18 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.  A lipid panel (total 
cholesterol, triglycerides, HDL, LDL) will be checked at every in-
person study visit. The interventionist will have access to all lipid 
fractions, but the algorithm will focus on non-HDL as the primary 
target. When a new lipid-lowering agent is prescribed, the 
prevention interventionist will call 2 weeks after initiation to discuss adherence and any possible side-effects. 
The interventionist will use an evidence-based approach to evaluation and management of muscle symptoms 
and other intolerances of statins as recommended by NLA guidelines.68,69 This approach will include evaluation 
Figure 7: Lipid treatment algorithm. 
Figure 6: Blood pressure treatment algorithm 

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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 lipid specialist. 
Relevant process evaluation data for aim 3: (1) frequency of BP and lipid algorithm use; (2) number 
of telephone contacts and total duration of time required to bring an elevated BP or lipid 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 lipid specialists.   
4. Home BP monitoring.35 Our justification for using home BP monitoring is that home BP measurements are 
reproducible with standard deviations of less than 3.1 mmHg for both systolic and diastolic measurements.70 In 
addition, home BP monitors are accurate and comparable to ambulatory BP monitors,71 a ‘gold standard’ of BP 
measurements. Home measurements have greater predictive power for mortality as compared to office-based 
measurements.72 All intervention participants will receive a home BP monitor, if they do not already have one, 
through the VA prosthetics department. They will be trained according to a developed protocol34 and 
documentation of proper usage will be recorded. The interventionist may also use video to determine if 
individuals are measuring their BP correctly at each intervention visit. Prior to each telephone contact, we will 
request BP values for the past two weeks using ANNIE with the goal of using the average of at least 3 values.  
Participants with poor BP control will receive interventionist calls every 2 weeks, with management changes 
made as described in component #4 below.   
Relevant process evaluation data for aim 3: (1) Frequency of home BP checks (average 
checks/week); (2) Number and nature of medication changes in response to home BP data. 
5. Support tools.  Evidence-based tools that do not result in provider fatigue or information overload 
effectively improve patient outcomes.73,74 We use these tools to assist the interventionist during the intervention 
phase:   
• 
An extended treatment cascade graphic for the interventionist that appears as a recurring pdf report.   
• 
The interventionist will regularly access names of specific patients who have fallen out of each cascade 
category. 
• 
Decision support tools for the protocolized prescription of BP and cholesterol medications.   
• 
Automatically calculated National Lipid Association treatment targets for LDL and non-HDL cholesterol.   
These tools will only be available to the interventionist during the intervention phase, but will then be made 
available to all providers after the intervention is completed. 
Relevant process evaluation data for aim 3: (1) number of times each tool is accessed; (2) 
proportion of subjects with missing data for NLA lipid targets tool. 
 
6. (Optional) Participant Support Group - These will be approximately monthly drop-in groups for any 
Veteran randomized to the intervention arm.  Study participants will be able to access the group only during 
their 12-month participation in the study. Groups will be for approximately 60 minutes and will be organized by 
a member of the study team who will function as a facilitator during the session.   The purpose of these groups 
is for the Veterans to talk with one another about their experiences, struggles and challenges in managing their 
blood pressure / cardiovascular risk. The groups will not be used to seek or obtain medical advice from a 
medical professional. Sessions will be conducted using a VA-approved videoconferencing platform, such as 
Cisco Webex or Microsoft Teams, when possible, or by phone, when needed. Research staff would provide 
the phone number or weblink to the events by the Veteran’s preferred method of communication (email, phone, 
mail, Annie SMS, secure messaging etc). These monthly support group sessions may be recorded (both audio 
and video, as is standard for Webex or Teams software) for quality control purposes only. No transcription will 
be done for the support group recordings; they are only for quality control purposes (e.g. to review the 
facilitator’s methods). Participants will be eligible to continue attending monthly support groups even after their 
participation in the study/intervention ends, as no data is collected during these visits. 
 
Aim 3: Qualitative Interviews for Process Evaluation 
A random subset of approximately n=27-40 intervention participants (4-16 from each site) will complete key 
informant interviews at the conclusion of the intervention. Participation in these interviews will be voluntary and 
discussed when they provide informed consent to the intervention (aim 2). Veterans will be paid $20 for 
completion of interview. In addition to collecting information from Veteran participants, we will also reach out to 
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we will collect feedback related to their thoughts on the intervention delivery and future 
sustainability/implementation. Feedback will be collected via VA-approved methods as written or oral 
questions, based on clinician’s preference and availability (VA encrypted email, VA REDCap survey, Microsoft 
Teams, and/or telephone calls). Providers/staff will not be compensated.  
For the Veteran participants who complete interviews, they may also be contacted 6-12 months after 
completing the intervention for a second brief interview. The purpose of these interviews to hear participants’ 
long-term perspectives from completing the study and developing a better understanding of the sustainability of 
the intervention.  
 
Risk 
This study is enrolling Veterans living with HIV. 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 among Veterans with HIV, it is 
important that they are not excluded from participation in this study. We will use VA CDW to identify the initial 
patient sample using the inclusion/exclusion criteria. Each site’s respective electronic medical record system 
(CPRS) will be used for a second screening level for information not readily available as normalized data in VA 
CDW prior to contacting patients.  If investigators identify any SAE outcomes of interim findings which have the 
potential of affecting participants’ health or welfare, the veterans as well as their PCP will be notified using 
secure VA notification processes.   
 
Potential risks 
a. 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 associated with asking questions relevant to a sensitive diagnosis 
like HIV.  
b. 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 study will have a 
history of hypertension so we expect to see abnormal systolic and diastolic 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 as soon as possible. 
c. Kidney disease and electrolyte imbalances: Some of the blood pressure agents used in the 
interventionist-managed protocols may cause acute kidney injury and electrolyte imbalances. Subjects 
with underlying kidney disease at baseline will be at higher risk. 
d. Drug-drug and Drug-disease interactions for ART treatment. Each site will have a clinical site 
leader who is an infectious disease doctor familiar with current CVD/HIV treatments to ensure that there 
are no drug-drug interactions. 
e. Other medication side effects: All medications have potential side effects. Medications used in the 
interventionist managed protocols will only be recommended by the interventionist 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 medication include but are not limited to: 
bradycardia, lightheadedness and orthostatic hypotension, lower extremity edema, kidney injury and 
electrolyte imbalances (see above), and myalgias.  
f. 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. 
g. Smoking and Alcohol Misuse. All subjects will be encouraged to quit smoking (if currently using), 
raising the possibility of withdrawal symptoms from nicotine dependence. Participants will also be 
screened for alcohol misuse.  
h. 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 

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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 Interventionist about some topics that are included in patient-
based intervention. We have not experienced any significant issues regarding this in our prior 
qualitative or mixed-methods studies with Veterans who are HIV+. However, subjects will be permitted 
to skip any topics that make them feel uncomfortable, and subjects will be informed that if they choose 
to discontinue the study at any time, this will not interfere with their usual medical care. 
 
Adequacy of Protection Against Risks.  The specific risk of participation are noted above; procedures for 
protection follow. 
 
a. Protection of participants’ identities and confidentiality: Because this study involves persons with 
HIV, 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 
interviewing, tracking, vulnerable 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 staff 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. When appropriate, material specific to interacting with persons living HIV and 
the sensitivity of the diagnosis will be provided to research staff as part of their training curriculum.  
 
b. 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, subjects in the education control are will be asked to contact their provider for follow-
up. [We will proactively address BPs for participants in the control group. If BP is identified by study 
staff as being high (>180/110), similar to prior trials), we will provide feedback to both the patient and 
their provider via developed CPRS template and/or phone calls. If no action is taken, the study 
physician at each respective site will follow up with the patients’ provider.]  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. 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 clinician 
investigators designated as the clinical contact for each site:. 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 

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>180, and/or DBP >110), participants will be asked to contact their 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 
healthcare 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 interventionist as soon as possible. The prevention interventionist will 
then generate a note to be entered into the electronic medical record and will communicate directly with 
the subject’s PCP. To facilitate the efficiency of this alert mechanism, the prevention interventionists will 
be encouraged to familiarize themselves with relevant clinic providers and staff and integrate 
themselves into the clinic workflow as completely as possible.  
 
c. Lifestyle Interventions (Smoking Cessation, Alcohol Misuse, Physical Inactivity: The 
interventionist will explore potential barriers to meeting recommended levels of exercise using 
motivational interviewing techniques as well as setting goals for exercise. The interventionist will screen 
for alcohol misuse using SBIRT for Veterans who screen positive for alcohol use and make referrals to 
the Primary Care-Mental Health Integration (PC-MHI) program were Veterans with alcohol misuse are 
more likely to receive care. Screening, brief intervention, and referral to treatment (SBIRT) is an integral 
part of nursing practice. The interventionist will screen for tobacco cessation (smoking, smokeless, e-
cig, vaping). Barriers to initiating and maintaining smoking cessation will be explored and benefits 
emphasized. Among those in the process of quitting smoking or recently stopped, strategies to maintain 
smoking cessation will be explored. The interventionist explored potential barriers to smoking cessation 
using motivational interviewing techniques and setting goals for smoking cessation. The interventionist 
will provide a direct referral to the smoking cessation clinic and ensure that the study physician puts in a 
prescription for NRI when appropriate. Additionally, the interventionist will provide resources related to 
these behaviors and when appropriate, refer individuals for follow-up care. 
 
d. Medication adverse effects, including kidney and electrolyte imbalances: All participants who are 
prescribed a clinically indicated new medication according the interventionist-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 interventionist about 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. 
 
e. Drug-Drug and Drug-disease interactions with ART. Each site will have a clinical site leader who is 
an infectious disease doctor familiar with current CVD/HIV treatments to reduce any potential drug-drug 
interactions.  Our three CVD/ID specialist and ID site specialist  will provide input on antihypertensive 
choice before initiation. If the patient’s ASCVD risk estimate is ≥5% over 10 years, based on current 
guidelines it is reasonable to begin moderate-intensity statin therapy. Antiretroviral therapy may 
adversely affect lipid levels, glycemic control, and endothelial function and has been associated with 
adverse changes in body composition (lipodystrophy). However, use of newer agents may lessen the 
metabolic derangements of antiretroviral therapy.  
 
 
Potential Benefits of the Proposed Research to the Subject and Others 
Potential benefits for subjects may include improved lifestyle and lower blood pressure with 

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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 cardiovascular disease, with the expectation that this would lead to consequent reduction in 
subsequent, cardiovascular complications and death. 
 
5.2 Recruitment Methods 
 
Aim 1: Formative Interviews and Design Team Meetings:   
Participants: There are two groups of participants for aim 1 
• 
Healthcare providers (both ID and primary care). up to 18 health care providers (n=6 
providers from each site, a mix of provider type (MD, RN, NP, PA, PharmD)  will participate. 
Providers will be recruited by purposive and snowball sampling. We will first interview providers 
to seek their guidance on key factors on which to select our Veteran informants.  
• 
Veterans with HIV: up to 18 Veterans (n=6 from each site) will participate.  They will be 
enrolled by purposive sampling.  
 
We will use nonprobability sampling techniques of purposive and snowball to recruit participants for this 
aim.  
A purposive sampling strategy is a “judgmental or expert sample” and is a type of nonprobability sample. The 
objective of purposive sample is to produce a sample that can be logically assumed to be representative of the 
population. This is often accomplished by applying expert knowledge of the population to select, in a 
nonrandom manner, a sample of elements that represents a cross-section of the population. To achieve 
representative, yet nonrandom sample of patients for our qualitative interviews, we will first query the context 
experts on the study team and at the site level to ascertain key variables (eg., age, race/ethnicity, sex, 
comorbidities) upon which to sample the eligible population of patients with HIV and CVD risk. Based on these 
typologies, we will query CDW based on these variables and then develop a purposive sample based on these 
characteristics.  In some instances, we will also use direct nominations by site leaders and providers, when 
feasible.   
We will then mail introductory letters to Veterans who meet these criteria using a strategy whereby Veterans 
may call a toll-free number to opt out.  The letters are on VAMC letterhead and signed by the study site PIs 
(attached).  If patients meet telephone screening criteria and are interested in participating, we will complete 
the informed consent process by telephone before scheduling the qualitative interviews. 
 
For providers, we will predominantly use a snowball sampling (ie., chain sampling, chain-referral sampling) 
which is another a nonprobability sampling technique. In snowball sampling, existing study participants help 
identify future participants from among their social network such that the sample group is said to grow like a 
rolling snowball. For this protocol, we will work with site leads to identify a beginning set of site providers. We 
will then ask these providers to nominate others they see as important to the implementation of the intervention 
while balancing mix of providers (eg. MD vs NP). In order to protect the identity of providers who are contacted, 
we will create a firewall between the study and management – that is, there will be no record for which 
management can be aware of which providers were contacted nor which providers agreed to participate.  We 
will contact providers by encrypted email, with introductory information about the study (attached).  Research 
staff will reach out to providers after the emails are sent to assess interest in participation, and will conduct the 

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informed consent process by phone before scheduling any interviews. Participation with providers can be done 
by all authorized communication methods approved by VA, such as email, Microsoft Teams, phone call. 
For Aim 1b (design meetings), we plan to consent approximately 10-20 design team members across the 3 VA 
sites: a mix of healthcare providers, and Veterans with HIV. These healthcare providers and Veterans will most 
likely be those who already participated in the Aim 1a qualitative interviews and expressed interest in the 
design meetings, but they will undergo another verbal consent process with specific details to the design 
meeting process. 
 
See table below regarding payment to Veterans for participation in the project. Providers/staff 
will not be compensated. 
 
Aim 2: Evaluate the 12-month efficacy of interventionist intervention 
Participants: We plan to enroll 300 HIV+ Veterans who are on suppressive ART with HIV-1 RNA <200 
copies/ml checked at least twice within the prior year if they have hypertension and receive care at the 4 clinic 
sites. Our plan is to enroll approximately 100 from each of the following sites the Durham VA Healthcare 
System, Cleveland VA Healthcare system, Baltimore VA HealthCare System and the Atlanta VA Healthcare 
System.  We may enroll more or less at the different sites depending on acceptance of study at the sites. Since 
site is one of our randomization strata enrolling more at one site will not impact analysis. Additionally, while 300 
is our enrollment goal, we may consent and randomize up to 310, to account for site differences, withdrawals 
and the scheduling availability and preferences of Veteran participants. 
 
The study programmer and statistician in Durham will use VA Corporate Data Warehouse to identify a sample 
population at each facility for Veterans enrolled in care at through either primary care clinics or infectious 
disease clinics. ICD-10 diagnostic and procedure codes will be used to identify patients meeting the 
inclusion/exclusion criteria. Research assistants will use each site’s respective electronic medical record 
system (CPRS) for a second screening level for information not readily available as normalized data in VA 
CDW prior to mailing letters. Research assistants will also be able to conduct chart reviews, to assess 
eligibility, for other study sites using Joint Longitudinal Viewer (JLV).  
 
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 V-EXTRA-CVD intervention 
components 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 
 

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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 
 
Specific recruitment strategies may vary at each site depending on the preferences of the clinic providers and 
Veteran populations, but will include a mix of the following methods: 
1. The research team will mail introductory letters to Veterans who meet eligibility criteria using a strategy 
whereby Veterans may call to opt out.  The letters are on VAMC letterhead and signed by the study site 
PIs. 
2. Medical providers in their clinics may talk to their patients about the study and refer potentially eligible 
and interested patients to the site’s research assistant.  
3. Study-specific flyers and brochures will be made available at each of the site’s clinics, allowing 
Veterans to self-select and call the research team for more information. 
The research assistant will contact potentially eligible Veterans and administer a screening questionnaire to 
further assess eligibility. This may be done by phone, or in-person (if a patient is already on-site for an 
appointment and able to meet with the research team). If patients meet screening criteria and are interested in 
participating, we will schedule an enrollment visit to coincide with an upcoming clinic appointment or the 
availability of the Veteran. If ≥ 30 days pass between initial chart review and date of consent, chart review may 
be repeated to confirm eligibility at time of consent. 
 
All enrolled participants will complete a baseline assessment which includes in-office BPs, lipid panels, and 
several health-related surveys (see section 5.5 study evaluations). On return visits at 4, 8 and 12 months all 
participants will similar assessments. Participants will be randomized during the baseline visit. 
 
Participants in both study arms will be paid a total of $150:  $50 for completion of the baseline questionnaires 
at the enrollment visit and $50 for completion of the 12-month blood pressure and lab outcome assessment 
and questionnaires. They will be paid $25 for completion of the 4 & 8 month blood pressure and lab outcome 
assessment.   These are the only study sessions that require in-person visits. If due to unforeseen reasons or 
closures, we are unable to obtain BP by study personnel, we may conduct VVC visit with study participant to 
observe the collection of self-monitored BP and schedule patient for lab collection within next 4 weeks.  The 
research assistant completing the assessments will submit the payment voucher following each visit after we 
receive the results of labs.    
Aim 3: Process Evaluation  
Participants: A random subset of approximately n=27-40 intervention participants (4-16 from each 
site) will complete key informant interviews at the conclusion of the intervention. Participation in these 
interviews will be voluntary and discussed when they provide informed consent to the intervention (aim 
2). Selection of VA providers will be based on those currently employed in ID or Primary Care clinics at 
the 4 study sites, and those who interacted with the study team during the intervention (most likely ID 
physicians whose patients enrolled in the study, and were responsible for making changes to 
medications after health coach recommendations). Veterans will be paid $20 for completion of 
interview. Providers/staff will not be compensated.   
 
Exploratory Aim: Cost Evaluation  
Participants: If effective, we will conduct a budget impact analysis and simulate 10-year cost-
effectiveness of the interventionist intervention.  The entire cohort of Aim 2 will be used in the budget 
impact analysis and the intervention cohort will be used in the 10 year cost effective analysis.  
 
 

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Participant payments: 
The research assistant completing the assessments will submit the payment voucher following each 
visit. Providers/staff will not be compensated.  
Aim 1 – Formative evaluation 
& adaptation 
Formative interview (n=18) 
Design Meetings to adapt intervention 
(n=6) 
Phone interview to review acceptability 
of intervention revisions (n=12) 
$20 
$120 per meeting 
($480 total) 
$20 
Aim 2 – Interventionist-led 
intervention 
In-person study outcome assessments 
(n=300) 
Months 0, 12 
Months 4, 8 
  
 
$50 each 
$25 each 
Aim 3 – Process evaluation 
Post-intervention qualitative interview 
(n=27-40), as well as 6-12 month post-
intervention sustainability interview 
$20 each 
5.3 Informed Consent Procedures 
Subjects for each aim will go through the informed consent process to participate in the study.  
Research staff (RA or PC) will read, review, and discuss consent documents with all potential 
participants prior to obtaining consent.  If the veteran appears confused or indicates a lack of 
understanding, the interviewer will attempt to identify the misunderstanding and to explain the study 
again. Any veteran who still does not comprehend the consent process and study will be excluded from 
the study. Veterans who understand the consent process and study and agree to participate in the 
study will be asked to provide consent either verbal or written. For those participants who provide 
written informed consent, the research assistant will keep the original signed and dated consent 
documents and will provide a copy of the signed documents to the subject. No veterans who have 
impaired decision-making abilities will be enrolled in any phase of the study.  These consent 
procedures will take place in a private room or office. Written consent and HIPAA forms will be kept in a 
locked filed cabinet within a secure office at each of the 3 sites. Verbal consent will be documented in 
RedCap & tracking database.  
Aim 1:  Formative Evaluation/Qualitative Interviews and Design Team Meetings.  These interviews and 
meetings will be done by telephone, with no in-person contact, therefore we will request a waiver of 
documentation of informed consent as well as waiver of HIPAA.  Research staff (RA, PC, or 
investigator conducting the interviews) will collect verbal informed consent from both the veteran and 
provider participants for Aim 1. Date of verbal consent obtained will be documented in tracking 
database or REDCap along with the name of the person who obtained consent.  
Aim 2: Intervention.  Once the veteran is screened and agrees to enroll, then written informed consent 
and HIPAA authorization will be obtained at the baseline visit.  These visits will be handled by the 
research assistant at each of the 3 sites. The project coordinator is also trained and able to assist with 
these visits.  All research staff (RAs and PCs) will be up to date on all CITI training and how to obtain 
and document informed consent.   
Aim 3: Process Evaluation:  Participation in this aim will be a voluntary addition when providing 
informed consent for the intervention (aim 2).  It will be covered by the same written consent and 
HIPAA authorization as Aim 2. For clinicians contacted for their feedback, language will be provided (by 
VA encrypted email or verbally on Microsoft Teams/telephone) related to providing consent 

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All study personnel will maintain certification of completed training in research ethics and confidentiality, 
data privacy and security.  The study/site PIs will meet with research staff before the study begins to 
review eligibility and study procedures including obtaining informed consent and documentation of 
informed consent and authorization.  If required by local site IRB/R&D/RCO, the research assistant will 
enter the research consent note into CPRS within 24 hours of the subject signing the consent and 
attach the scanned informed consent, HIPAA authorization as soon as possible but no later than 14 
days from the signed consent. 
5.4 Inclusion/Exclusion Criteria 
 
The same inclusion and exclusion criteria is used for Veterans enrolled in all aims.   
 
Inclusion Criteria 
Exclusion Criteria 
Veterans with HIV 
Aim 1: N= 18 
Aim 2: N= 300 
Aim 3: N = 27 
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 18 months 
(assessed via chart 
abstraction) 
4. Hypertension: defined as 
having 2 recent outpatient 
BP measurements in the 
last 18 months to show 
systolic BP ≥ 130 and/or 
diastolic ≥ 90 mmHg OR 
being prescribed anti-
hypertensive medication 
(assessed via chart 
abstraction) 
5. Veteran at one of the sites 
participating in the study 
 
1. Severely hearing or speech 
impaired, or other disability that 
would limit participation 
2. In a nursing home at baseline 
and/or any long-term care 
facility. Individuals will be 
censored at the point of entering 
nursing home care  
3. In-patient psychiatric care  
4. Diagnosis of dementia or active 
psychosis 
5. Terminal illness with life 
expectancy < 4 months (ex. 
Metastatic cancer, Hospice care,) 
6. Recent (<90day) hospitalization 
for CABG, MI, stroke) 
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. No reliable access to telephone 
services  
10. Currently enrolled in a competing 
research study (e.g. an 
intervention that may impact BP 
management) 
 
Providers 
(infectious disease 
and primary care)  
Aim 1: N= 18 (2 
HIV MDs, 2 PCPs, 2 
RNs per site)  
Aim 3: N = 6 
1. Have a panel of at least 10 
veterans with HIV.  
1. Not a provider at one the 3 
participating facilities 
2. PI is a co-investigator on the 
study.  
 
Table: Antihypertensive Medications –  

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Beta Blockers 
CARVEDILOL 
ESMOLOL 
METOPROLOL 
TIMOLOL 
BISOPROLOL 
NADOLOL 
ACEBUTOLOL 
 
ATENOLOL 
BETAXOLOL 
LABETALOL 
PINDOLOL 
PROPRANOLOL 
NEBIVOLOL 
PENBUTOLOL 
SOTALOL 
Alpha Blockers 
SILODOSIN 
TAMSULOSIN 
TERAZOSIN 
 
 
 
DOXAZOSIN 
ALFUZOSIN 
PRAZOSIN 
 
Calcium 
Channel 
Blockers 
AMLODIPINE 
NICARDIPINE 
AMLODIPINE/CELECOXIB 
CLEVIDIPINE 
ISRADIPINE 
NISOLDIPINE 
 
 
AMLODIPINE/ATORVASTATIN 
DILTIAZEM 
NIFEDIPINE 
VERAPAMIL 
FELODIPINE 
NIMODIPINE 
 
Antihypertensi
ve 
Combinations 
ALISKIREN/HYDROCHLOROTHIAZIDE 
AMLODIPINE/PERINDOPRIL 
ATENOLOL/CHLORTHALIDONE 
CANDESARTAN/HYDROCHLOROTHIAZIDE 
CAPTOPRIL/HYDROCHLOROTHIAZIDE 
HYDROCHLOROTHIAZIDE/IRBESARTAN 
HYDROCHLOROTHIAZIDE/LOSARTAN 
HYDROCHLOROTHIAZIDE/METHYLDOPA 
HYDROCHLOROTHIAZIDE/PROPRANOLOL 
AMLODIPINE/BENAZEPRIL 
BENDROFLUMETHIAZIDE/NADOLOL 
EPROSARTAN/HYDROCHLOROTHIAZIDE 
FOSINOPRIL/HYDROCHLOROTHIAZIDE 
HYDROCHLOROTHIAZIDE/LISINOPRIL 
HYDROCHLOROTHIAZIDE/METOPROLOL 
HYDROCHLOROTHIAZIDE/MOEXIPRIL 
HYDROCHLOROTHIAZIDE/TELMISARTAN 
 
 
TRANDOLAPRIL/VERAPAMIL 
AMLODIPINE/OLMESARTAN 
AMLODIPINE/VALSARTAN 
AZILSARTAN/CHLORTHALIDONE 
BENAZEPRIL/HYDROCHLOROTHIAZIDE 
BISOPROLOL/HYDROCHLOROTHIAZIDE 
ENALAPRIL/HYDROCHLOROTHIAZIDE 
HYDRALAZINE/ISOSORBIDE 
SACUBITRIL/VALSARTAN 
AMLODIPINE/HYDROCHLOROTHIAZIDE/OLMES
ARTAN 
AMLODIPINE/HYDROCHLOROTHIAZIDE/VALSAR
TAN 
AMLODIPINE/TELMISARTAN 
HYDROCHLOROTHIAZIDE/OLMESARTAN 
HYDROCHLOROTHIAZIDE/QUINAPRIL 
HYDROCHLOROTHIAZIDE/VALSARTAN 
 
Antihypertensi
ves, other 
CLONIDINE 
METHYLDOPATE 
RIOCIGUAT 
TADALAFIL 
GUANABENZ 
GUANFACINE 
MECAMYLAMINE 
LOFEXIDINE 
MACITENTAN 
METHYLDOPA 
METYROSINE 
HYDRALAZINE 
ILOPROST 
SILDENAFIL 

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MINOXIDIL 
 
SODIUM NITROPRUSSIDE 
 
Peripheral 
Vasodilators 
ISOXSUPRINE 
PAPAVERINE 
 
 
Thiazides / 
Related 
Diuretics 
HYDROCHLOROTHIAZIDE 
CHLOROTHIAZIDE 
CHLORTHALIDONE 
 
INDAPAMIDE 
METOLAZONE 
 
Loop Diuretics 
FUROSEMIDE 
ETHACRYNIC ACID 
TORSEMIDE 
BUMETANIDE 
 
Carbonic 
Anhydrase 
Inhibitor 
Diuretics 
DICHLORPHENAMIDE 
METHAZOLAMIDE 
ACETAZOLAMIDE 
 
 
Potassium 
Sparing / 
Combination 
Diuretics 
HYDROCHLOROTHIAZIDE/SPIRONOLACTONE 
HYDROCHLOROTHIAZIDE/TRIAMTERENE 
AMILORIDE 
 
 
AMILORIDE/HYDROCHLOROTHIAZIDE 
EPLERENONE 
SPIRONOLACTONE 
TRIAMTERENE 
 
Diuretics, other 
CAFFEINE/MAGNESIUM SALICYLATE 
MANNITOL 
SPIRONOLACTONE 
PAMABROM 
 
ACE Inhibitors 
BENAZEPRIL 
CAPTOPRIL 
ENALAPRIL 
FOSINOPRIL 
QUINAPRIL 
 
LISINOPRIL 
MOEXIPRIL 
RAMIPRIL 
ENALAPRILAT 
TRANDOLAPRIL 
PERINDOPRIL 
Angiotensin II 
Receptor 
Antagonists  
AZILSARTAN 
CANDESARTAN 
EPROSARTAN 
IRBESARTAN 
LOSARTAN 
OLMESARTAN 
TELMISARTAN 
VALSARTAN 
 
5.5 Study Evaluations 
 
The table below lists which measures are collected from participants at each time point in the 
study.  Data is recorded by the research assistant into secure study tracking SQL database or 
RedCap. The study team will develop an acceptable standardized time window for data 
collection around each timepoint.  
Study visits/interactions: 
Aim 1: Formative Evaluation  
 

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Qualitative Interview  
x 
Adaptation Virtual meeting  
x 
Revision Qualitative Interview 
x 
Aim 2: Intervention 
Intervention 
Usual Care 
Enrollment Visit  
(baseline measurements) 
x 
x 
Intervention Call – 1 week 
after enrollment visit with 
Interventionist 
x 
 
Follow-up Intervention Call – 2, 4, 6, 
8, 10,12 month after first call with 
Interventionist 
x 
 
Adhoc check in call/video 
visits for BP/Statin med 
adjustments  
x 
 
4, 8, 12 month outcome 
measurements –in person visit* with 
RA (to include measuring height, 
weight, BP, waist, and lipid panel at 
lab) 
x 
x 
Aim 3: Process Evaluation 
Feedback on the intervention 
collected by phone.   
x 
 
Note: * if in-person study visits are discontinued for reasons out of our control or for pandemic 
closure we will convert them to VVC visits to capture BP outcome and schedule participants for 
labs with 4 weeks of BP collection. We will accept clinical labs for same lab if they have been 
collected within time frame. 
 
Patient surveys for each time point are attached at the end of this document. 
Data element 
Source(s) 
Time period  
Aim 1: Formative Evaluation  
Perceptions of the self-management for CVD, 
HIV. Lifestyle change and medication adherence.  
Audio recordings and field 
notes from qualitative 
interviews 
Aim 1:  
 
 
 
Aim 2: Intervention/ Survey  
 
 
Chart Abstraction/Review and screening 
Site CPRS medical 
records/CDW 
Pre enrollment 
Hypertension diagnosis 
Site CPRS medical 
records/CDW 
0, 12 
HIV + diagnosis, HIV history (prior labs, treatment 
and appointments), recent hospitalizations and 
ED visits, MOVE program participation 
Site CPRS medical 
records/CDW 
0 
Demographics, family history of CVD, health 
literacy, prior home BP use, technology use, life 
chaos, loneliness, pain, housing and food 
insecurity, financial strain, anxiety and depression, 
physical function 
Self-reported survey 
responses 
0 
Medications, comorbidities, labs, alcohol use 
Site CPRS medical 
records/CDW 
0, 4, 8, 12 
 
Health behaviors such as physical activity, diet, 
tobacco use, medication adherence, sleep, stress, 
Self-reported survey 
responses 
0, 12  

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Data element 
Source(s) 
Time period  
alcohol and substance use 
Aim 3: Qualitative Interviews 
 
 
Perceptions of CVD risk, self-management 
strategies and barriers, and intervention delivery 
strategy. For example, we will ask participants 
which aspects of the intervention were most and 
least helpful, appropriateness of the number and 
length of telephone sessions, and ways we may 
be able to further improve the intervention. 
Audio recordings and field 
notes from semi-structured 
interviews 
12 
Optional sustainability interviews: 6-12 months 
after completing intervention, to hear participants’ 
long-term perspectives from completing the study 
and developing a better understanding of the 
sustainability of the intervention 
Audio recordings and field 
notes from semi-structured 
interviews 
18 - 24 months 
Exploratory Aim: Cost Impact Analysis 
 
 
Hospitalizations, Labor & Capital cost  
CDW/Self-reported data 
0, 12 
 
5.6 Data Analysis 
Aim 1: Formative Evaluation. Data will be analyzed by the Qualitative team in collaboration 
with PI.  
Analysis for Aim 1a: Quantitative data (e.g., medical history, perceptions of CVD risk) will be summarized and 
used to describe study samples. After redacting all identifying information, verbatim transcriptions of recorded 
interviews will be entered into NVivo 12. A quality assurance protocol for qualitative analysis will be built into 
data management and analysis; 25% of the transcripts will be checked to verify accuracy of the transcriptions 
and 10% will be double-coded to ensure inter-coder reliability of 80% or greater.75   
All responses will be analyzed using standard thematic analytic techniques for qualitative data: 
identification of themes/domains;76 coding or classification of participants’ responses by these themes 
performed independently by two team members; resolution of any coding discrepancies will be done by a third 
team member.77 To ensure consistency, a codebook and dictionary will be developed to create universal 
definitions for each code. The architecture of the interview guide domains - informed by our theoretical lens of 
RE-AIM, Self-Regulatory Theory, and the Information-Motivation-Behavioral skills model -  will drive the initial 
coding of our data. Yet, significant inductive (emerging) codes will also be identified. Coded items will be 
grouped together into distinct themes. Finally, the analytic team will work from the coded data to merge 
findings into a report of findings to aid in the intervention development.28,38,78 Key findings will be abstracted 
into a matrix and mapped to existing intervention components to aid integration and map adaptation to inform 
participatory, iterative design process in Aim 1b. 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. Findings from these interviews will be presented back to the 
study team and site leadership to inform context-specific adaptation of the intervention. 
 
Analysis for Aim 1b: We will use a participatory, iterative design process as the analytic approach for Aim 
1b.53-55 .. The results will be a documentation of key adaptations of the evidence-based practices to inform 
intervention redesign to optimize clinical impacts and feasibility and acceptability of innovation uptake.  
 
During brainstorming, the team will review the data obtained during the baseline assessment on perceptions 
of ASCVD risk and barriers and facilitators of ASCVD preventive care obtained during Aim 1a. The team will 
brainstorm ideas to refine the intervention in response to these data. Ideas will be captured in a structured, 
written format for the next phase.  
 

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In the conceptualization phase, the team will evaluate advantages and disadvantages of ideas generated 
during the brainstorming phase, and will develop concrete changes (ie., adaptations) to the intervention. For 
example, if the team decides to include the name of the provider (PCP or HIV specialist) responsible for BP 
and lipid management in the intervention program, we will discuss its feasibility. All final adaptations will be 
captured in a structured, written form to aid in implementation in the revision phase.  
 
The creation and revision phases will involve the refinement of treatment protocols, manuals of procedures, 
and educational materials. Once the adaptation of the intervention is completed, we will present the adapted 
model to our Veteran Engagement Quorum  and up to 9  intervention staff from each of the three sites to 
assess acceptability.56  We will document any further adaptations resulting from these engagements in a 
structured written format to be implemented into the treatment protocols, manuals of procedures, and 
educational materials. 
 
We will also analyze the perspectives from design team members in the final meeting about their experience 
participating in the Human Centered Design process. Content analysis of individual surveys and group 
discussions will be performed by the qualitative staff members and coded based on emergent themes 
captured. Core outcomes of interest for the surveys and discussions will include: a) previous design team 
experience; b) comprehension of the design team experience; c) thoughts on the design team process for the 
intervention; d) reflections on each phase of the human-centered design approach; and e) perceptions of the 
final intervention model.   
 
Analysis for Aim 1c:  
We will describe the HTN care cascade among PWH over a period of 5 years based on data definitions 
described above. To estimate proportions along each cascade, we will conduct descriptive analyses 
and obtain frequencies and percentages of Veterans at each previously defined step compared with the 
preceding step. We will conduct univariate analyses to describe demographic and baseline 
characteristics of the cohort. Means and SDs will be obtained for continuous variables, whereas 
percentages and frequencies will used to describe categorical variables. We will stratify the data into 2 
subpopulations: HIV and HIV/HTN and compare baseline characteristics of these 2 subgroups.  
 
Aim 2: intervention.  Data will be analyzed by PhD & Master Statistician in collaboration with 
PI 
Analysis: 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 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 models79 (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,
 
where 
 represents the outcome of interest (i.e., SBP or non-HDL) for patient i at time j. We will fit a common 
intercept and arm is the intervention group indicator. Similarly, time will be classified, where for example, 
 is a dummy variable equal to 1 for the 12 month time point. Random intercepts will be included 
for each individual to account for correlation among repeated measurements over time. The primary analytic 
model will adjust for clinic site and hyperlipidemia status. 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, 
, the 
estimated difference in outcome between arms at 12 months, will be the primary effectiveness outcome 

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assessed. 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.  
Our primary analysis will include all available study-collected data. A sensitivity analysis will be conducted by 
filling in missing data in the following manner: 
1. 
Use all available study-reported data. 
2. 
If missing study-reported value  use the SBP or non-HDL cholesterol value if available in the 
EMR in a 2 month window from the target data for that time point 
3. 
If missing EMR-reported value  assess whether the outcome has >10% missing remaining. 
a. If yes, ≥10% missing  use multiple imputation 
b. If no, <10% missing  do not use multiple imputation, include only study- and EMR-reported 
values 
The final determination whether to use multiple imputation is separate for SBP and non-HDL cholesterol 
outcomes; SBP could meet the criteria and non-HDL does not, or vice versa. 
If multiple imputation is indicated, we will use 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 and carefully examine and describe any discrepancies 
found between the primary and missing data analyses. 
Attrition bias. As part of our examination of missing data, we will assess differences in baseline 
characteristics (e.g., clinic site, demographics, clinical values, medical history) by retention at each follow up 
time point. We will use two sample t-tests (or Wilcoxon rank sum tests) for continuous variables and χ2 tests for 
categorical variables.  
Power. The power calculation for this study was based on our prior nurse-led BP intervention,35 a meta-
analysis of lipid-lowering medication adherence interventions,80 and baseline BP 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 145 
mmHg for both arms, with a reduction in the education control arm of 1 mmHg by 12 months. For the 
intervention arm, we evaluated effect sizes (differences from education control at 12 months) of 5-7 mmHg. 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 interventions at our sites (80-88% retention at 12 
months).33,35,81 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 132 mg/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 10-20 mg/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 error rate of 0.05.  Based on results, we 
will have >80% power to detect a 6 mmHg lower systolic BP and >90% power to detect a 15 mg/dL lower non-
HDL cholesterol in the intervention arm vs. education control. Table 4 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 events,82 and a 15 mg/dL improvement in cholesterol is 
associated with ~10% decrease in clinical ASCVD events.83 
Pre-specified sub-group analyses of the primary and secondary outcomes will include clinic site, sex, and 
baseline ASCVD risk category (10-20%, >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 
Table 4: Sample size estimates to detect a range of plausible and clinically significant effect sizes 
 
BP Effect Size 
Non-HDL Effect Size 

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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). 
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, 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. 
 
Analysis for Aim 3: The Process Evaluation:  Data will be analyzed by the Qualitative team  in collaboration 
with PI. The analysis for this aim will use a mixed-methods approach. We describe these by outcome below.  
 
ASCVD Risk: We will assess changes in the perceived ASCVD risk scale between intervention and control 
group using t-tests and will examine correlations between changes in perceived risk and changes in clinical 
outcomes.  
Additionally, we will collect additional data on the context of the intervention by assessing changes in 
perceived ASCVD risk and care team networks.  In a group of up to 27 participants, we will evaluate how 
perceptions of ASCVD risk qualitatively changed over the course of the intervention. As above, qualitative 
interviews with participants  will be analyzed using standard thematic analytic techniques for 
qualitative data: identification of themes/domains;76 coding or classification of participants’ responses 
by these themes performed independently by two team members; resolution of any coding 
discrepancies will be done by a third team member.77 To ensure consistency, a codebook and 
dictionary will be developed to create universal definitions for each code.  
 
Process Outcomes analysis: The process evaluation will collect data on key implementation measures across 
the following six categories: fidelity (quality), dose delivered (completeness), dose received (exposure and 
satisfaction), recruitment, reach (participation rate), and context.84 Key measures of interest for each 
component of the intervention are described above under Aim 2 “Intervention components.”  
 
intervention relevant data: (1) frequency of BP and lipid algorithm use; (2) number of telephone contacts and 
total duration of time required to bring an elevated BP or lipid 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 lipid specialists. 
Home BP monitoring relevant data: (1) Frequency of home BP checks (average checks/week); (2) Number 
and nature of medication changes in response to home BP data. 
Support tools relevant data: (1) number of times each tool is accessed; (2) proportion of subjects with 
missing data for NLA lipid targets tool. 
 
Exploratory Aim: If effective, [we will conduct a budget impact analysis] and simulate 10-year cost-
effectiveness of the intervention. Data will be analyzed by the Economic team (Drs. Kaufman and Smith) in 
collaboration with PI. 
Health economic analyses.  If the intervention is effective, we will conduct a budget impact analysis of 
the intervention costs at 12 months and simulate cost-effectiveness at 10 years. We plan to simulate 
10-year rather than lifetime outcomes due to the lack of validated data for CVD outcomes past 10-years 
in an HIV cohort. We will apply a VA perspective in cost evaluation. To assess the cost-effectiveness of 

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the intervention, we will examine the difference in average health care and intervention costs between 
treatment and control arms (incremental cost), and difference in average effectiveness between 
treatment and control arms to calculate an incremental cost-effectiveness ratio (ICER) that summarizes 
the relative costs and benefits of the interventionist-led intervention.  
 
Budget impact analysis: Fixed and marginal costs over the 12-month study period will be described 
using VA and study data. One-way sensitivity analyses will be used to demonstrate the impact of 
uncertainty in resource utilization. The unit cost will be multiplied by the estimated number of people 
potentially eligible for the intervention to project the budget required to scale the intervention. 
 
Cost effectiveness analysis: Ten year ICERs are defined as the incremental cost divided by the 
difference in Quality-Adjusted Life Years (QALYs) to enable comparisons to other interventions under 
consideration for broader translation. To simulate 10-year outcomes, we will leverage the existing 
evidence on costs and utilities associated with hypertension control as well as competing risks and 
utilities specific to HIV populations with ART in high-income countries.85-87 The ACC/AHA pooled cohort 
equations for ASCVD risk will be applied to estimate 10 year ASCVD incident event rates. In the 
intervention scenario, we will apply relative risk ratios for ASCVD events associated with blood 
pressure-lowering therapies using the ACC/AHA systematic reviews informing the Million Hearts tool.88 
We will use TreeAge to build a cohort-based simulation model, and apply parameter values that have 
been validated in prior cost-effectiveness studies. Costs for CVD preventative therapies will be 
extended out to the end of the period, applying published adherence/maintenance rates. Discount and 
inflation rates of 3% will be applied to out-year costs. One-way sensitivity analyses may be used to 
evaluate the impact of Reach and Maintenance on 10 year cost effectiveness. We will assess variability 
in the estimate using a probabilistic Monte Carlo sensitivity analysis with 1000 iterations and generate 
an acceptability curve presenting the percentage of simulation iterations for which the intervention 
achieves cost-effectiveness thresholds over a range of willingness-to-pay values. 
5.7 Withdrawal of Subjects 
Participant withdrawal.  Because this is a minimal risk study, it is unlikely subjects will be withdrawn due to 
safety concerns. Participants are free to withdraw from the study at any time for any reason. However, the 
study team will meet weekly to determine cumulative enrollment and drop-out rates, as well as charts of these 
rates over time so that we can detect any changes. Any individuals who decline to participate or drop out of the 
study will be asked to describe a specific reason for this choice. These reasons will be tracked in the study 
database. We will regularly review the numbers of patients who cite different reasons for refusal / drop-out, and 
if there are any factors that can be modified in our study approach, we will take action as appropriate. The 
project coordinator will also present, at each meeting, enrollment and drop-out rates according to gender, race, 
and clinic. If any differences are observed, we will examine refusal / drop-out reasons endorsed by these 
different groups to detect whether there are any systematic study-related processes that may be influencing 
these differences.  
Investigator withdrawal: Participants should normally be withdrawn from the trial if a serious adverse 
event (SAE) occurs. The below are the reasons an investigator may withdraw a participant from the 
study.  
1. The investigator considers it in the best interest of the veteran that they or she is withdrawn 
2. A Veteran displays abusive behavior towards staff 
3. A patient is female and becomes pregnant during the study 
4. The study is suspended or cancelled 
 
The reason and date of withdrawal will be documented by research staff in the study tracking database.  
For patients in the intervention arm who no longer want to participate in the intervention, they will still be 
eligible to complete the outcome assessments (at months 4, 8, 12) and receive payment for completion 
of those visits.  
5.0 
Reporting 

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Unexpected and serious adverse event reporting:  
Because this is a minimal risk study involving only a telehealth based intervention, we do not anticipate serious 
adverse events due to the study.   However, safety information will be monitored at each interaction with the 
patient by the Interventionist via telephone sessions and the Research Assistant at outcome visits.  Specific 
information regarding safety collected during telephone calls and visits with the research assistants will be 
summarized for reporting. Due to the age range and health conditions (HIV, hypertension, hyperlipidemia, 
cardiovascular disease, physical inactivity, smoking) of the patients identified for participation in the study, 
hospitalizations and other health events, including diagnosis of new medical conditions, surgeries, ER visits, 
MI, Stroke, falls and death, unrelated to the study are expected.   Any events that fall into one of these 
categories will be reported at continuing review.  Additionally, we expect that some patients may be 
uncomfortable answering survey questions or have pain and bruising as a result of blood draw for labs, which 
is similar to usual medical care. It is also expected that participants will miss monthly phone calls during the 
required time window and we will not consider either of these events protocol deviations.   A study physician 
will be on call at all times at their site. There will not be a data monitoring committee for the study.  The PI, site 
PIs, study Statistician, and project coordinator will serve this role.  All adverse events will be reviewed by the PI 
and Site PIs, the study statistician, and the project coordinator.  All sites will be responsible for reporting SAEs 
to the PI in Durham as soon as the reporting individual becomes aware of the occurrence.  Durham will be 
responsible for conveying information from each site to the VA Central IRB.  The VA Central IRB Table of 
Reporting Requirements will be used to guide all of our reporting decisions, with time windows given for each 
type of report.  
6.0 
Privacy and Confidentiality 
 
Protected Health Information (PHI) will be used and disclosed among members of the study team.  It will not be 
disclosed outside of VHA.  PHI will be obtained from existing sources including medical records and clinical 
databases for recruitment purposes and looking at VA expenditures and utilization.  PHI will be obtained 
directly from participants as they are screened over the phone, attend the consent visit and complete 
interviewers and outcome assessment. PHI will also be obtained directly from veterans through their 
participation with interventionist and qualitative interviews.   
Of primary importance in all study activities will be the security and protection of veterans’ protected health 
information (PHI).  We will take several measures to secure the data. We will only collect the data 
necessary for the study. All electronic data will be stored on a secure VA server, rather than on individual 
desktop or laptop computers.  
To further minimize any risks regarding privacy of individuals, we will take specific measures to protect both 
paper and electronic data. Except when required by law, participants will not be identified by name, social 
security number, address, telephone number, or any other direct personal identifier in study records.  
Subjects will be assigned a random study ID and the linkage file will be stored separately from their study 
data. All electronic data will be stored on secure VA servers in folders and databases accessible only to 
study personnel whose job functions require access to this information. We will minimize the use of paper 
data collection by entering information from telephone screening interviews, baseline and follow-up 
assessments, and intervention tracking directly into a computer database. Any paper-based documents 
(i.e., consent form) will be stored in a locked filing cabinet in a locked office. Any paper documents that 
must be transported to / from clinic enrollment sites will be carried in a locked briefcase.   
Training and authorization of access:  Only individuals officially assigned to the study team will have 
access to individually identifiable information about human subjects. All study team members will have 
completed VA’s required human subjects training, training in research ethics and confidentiality, data 
privacy and security.  Study team members will be included on a staff listing and removed should they end 

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participation on the study.  Prior to beginning the either the qualitative interview, a verbal consent script will 
be reviewed with the participant and verbal willingness to continue participation will be captured at the 
beginning of the audio recording. Study data will only be accessible to key personnel whose job functions 
require access to these data.  In the event of improper use or disclosure, the VA Central IRB will be notified 
within one hour of becoming aware of the incident, and well as reporting the incident to the local VAHCSA 
Durham, Cleveland and Baltimore research oversight authorities as per local protocol in compliance with 
IRB, privacy and compliance officers, as well as the medical center director. 
Physical controls:  Software will be provided by the Durham VA Center of Health Services Research and 
the VINCI workspace. Recording and transcription of the qualitative interviews will be conducted utilizing 
VA approved software installed and configured by VA OI&T personnel.  Audio recordings will be captured 
using WebEx or MS Teams as the software to record the audio portion of the patient interviews. 
WebEx/Teams recordings will be saved directly to the restricted study folder on the R drive. We will use the 
approved version of Audacity software (http://trm.oit.va.gov/ToolPage.aspx?tid =5566#) to edit the audio 
file in the study folder on the HSRD VA project server prior to it being transcribed by the SLC team. 
Additional, software includes packages for data management (Microsoft SQL 2012), statistical analysis 
(SAS), Qualitative (NVivo, Atlas.ti), Tree Age, word processing (MS Word) and other specialized software 
(CATI). The primary database engine technology will be Microsoft SQL 2012, a relational database 
management system. All of the computerized data entry systems are backed by a series of related SQL 
data tables that will reside on certified and accredited VA Servers that are located in the Durham VA 
Medical Center IRM Server Room and the VINCI data center. All data transactions within and between 
systems will run through controlled, secure transactions to ensure the preservation of database integrity 
and privacy.  
The server power protection system is configured to page Office of Information and Technology (OIT) and 
center personnel upon detecting problems and sends a test notice weekly. Data are backed up to tape and 
backups are run daily. Center operating systems, database servers and internet information servers are 
patched monthly or more frequently for critical updates. Individual workstations, desktop PCs or laptops, 
are patched using the VA standard and laptops are encrypted using the VA standard tool Encryption. 
Workstations are equipped with anti-virus and firewall software. PHI is handled according to appropriate 
Health Insurance Portability and Accountability Act of 1996 (HIPAA) privacy and security regulations. 
Research staff who work with PHI are required to complete all appropriate HIPAA and information security 
training. 
The information technology solution that will serve to facilitate research activity will be based on a series of 
asynchronously connected database applications over which a comprehensive data model is deployed. 
Each database application will function independently as a discrete system. All data transactions within and 
between subsystems will run through controlled, secure transactions to ensure the preservation of 
database integrity and privacy. Study data will be maintained on secure servers for the duration of the 
study and for a period of time after the completion of the study that will be compliant with all VA regulations 
in place at the time of study closure. Access to the data is only granted to IRB-approved study personnel 
via approved software applications used for study participant tracking, data collection, and reporting. 
We do not plan to apply for a Certificate of Confidentiality. We recognize the diagnosis of HIV is a sensitive 
subject.  The study focus is on addressing the cardiovascular needs of the patients and having a certificate 
of confidentiality would potentially limit our ability to provide care coordination between the research 
interventionist and the primary care or infection disease doctors.  We also want to provide clear 
transparency regarding recommendations our study team is making to patients for the cardiovascular care 
vs other care they may be receiving. We do not believe that we are putting the veterans at more risk by not 
applying for a certificate on confidentiality.  
Once data has been analyzed, final deidentified data sets will be created for the study. Patients who 
participated in the project will be sent a summary letter to thank them for their participation as well as 
provide them with de-identified summary information regarding study participants.   We will take the 
following steps to ensure that the information shared maintains the protection of patient privacy.   
Publications from this research will be made available to the public through the National Library of Medicine 
PubMed Central website within one year after the date of publication and study results will be available on 

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Clinical Trials.gov within 1 year of the final follow-up with last study participant.   A local privacy officer and 
study statistician will certify that the dataset contains no PHI prior to distribution. Data will be provided to 
requester in electronic form. Final data sets will be maintained locally until enterprise-level resources 
become available for long-term storage and access. Guidance on request and distribution processes will 
be provided by ORD. 
No date or specimens will be banked in the study.  
1. Lists of Data Reviewed and/or Collected for Screening/Recruitment and Conduction of Study:  
The Personal Health Information that will be obtained, used, and/or shared for this study includes:   
Identifier(s) 
Source(s) of Health Information 
 Names 
 Medical history & physical exam information 
 All geographic subdivisions smaller than a 
State, including street address, city, county, 
precinct, and zip code.  Describe: Address, City, State, 
Zip 
 Photographs, videotapes, audiotapes, or 
digital or other images 
 All elements of dates (except year) for dates 
directly related to an individual, including birth date, 
admission date, discharge date, visit or treatment 
dates, etc.; and all ages over 89,  Describe: birth 
date, admission date, discharge date, visit or treatment 
dates, lab date, Dx date 
 Biologic specimens (e.g., blood, tissue, 
urine, saliva). Describe: blood samples to measure 
lipid profile 
 Telephone numbers 
 Progress notes 
 Fax numbers 
 Diagnostic / Laboratory test results 
 Electronic mail addresses (needed for VA Video 
Connect & ANNIE SMS, support group technology used 
in intervention) 
 Operative reports 
 Social Security Numbers 
 Imaging (x-ray, CT, MRI, etc.) 
 Medical record numbers 
 Discharge summaries 
 Health plan beneficiary numbers 
 Survey / Questionnaire responses 
 Account numbers 
 Billing records 
 Certificate and/or license numbers  
 HIV testing or infection records 
 Vehicle identifiers and serial numbers, including 
license plate numbers  
 Sickle cell anemia information 
 Device identifiers and serial numbers 
 Alcoholism or alcohol use information 
 Web Universal Resource Locators (URLs) 
 Drug abuse information 
 Internet Protocol (IP) address numbers 
 Mental health (not psychotherapy) notes 
 Biometric identifiers, including finger & voice 
prints 
 Psychological test results 
 Full-face photographic images and any 
comparable images 
 Genetic testing 
 Any other unique identifying number, 
characteristic, or code, describe :  
Anonymous/Randomly assigned study ID#  
*Note: This is not the unique code assigned to 
otherwise de-identified health information for re-
identification purposes. 
 Other, describe:        
 
  All non-Veterans enrolled in this study will receive the VA Notice of Privacy Practices (NOPP) and are 
requested to sign the acknowledgment form.  The signed acknowledgment form will be maintained with the 
research records. 
 
2. Data and/or Specimen Acquisition:   

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Data for this study will be collected through (check all that apply): 
  Prospective data and/or specimen collection obtained from participants.  Provide description of processes:  
We will survey participants during their participation in the study (in-person visits every 4 months).  We will also 
place lab orders for each in-person visit (every 4 months) to collect lipid profile. The study requires use of some 
individually identifiable data, including participant names, street address, city, county, zip code, telephone 
number, email to enroll in ANNIE SMS and VA Video Connect and Social Security number to complete 
telephone screening, send recruitment letters. We will collect the minimum amount of study data required to 
complete study aims involving recruitment, outcome assessment and reimbursement. Screening and outcome 
data will be collected in the currently approved version of REDCap.  
  Retrospective data collection and/or specimens obtained from medical chart review/data access.  Describe 
how data will be obtained (e.g., fileman, CDW, etc.):  We will use the current VA CDW/VINCI resources to 
identify the necessary participants with the requested inclusion/exclusion criteria. Using the real SSNs from 
that subset, we will retrieve current mailing addresses, telephone number, as well as the specific medical 
record data (using approved VA data bases) via the VHA Corporate Data Warehouse (CDW) dataset via the 
VINCI or another secure platform. We will perform medical chart review to assess study eligibility using CPRS 
or JLV. 
  Retrospective data collection and/or specimens obtained from an IRB-approved data and/or specimen 
repository.  Indicate the repository source including name, VA location, and IRB number:       . 
3. Level of Data:   
The following level(s) of data will be acquired/maintained for this study (check all that apply): 
  Identifiable—Data contains direct identifiers.   
  Coded—Data linked to a specific by a code rather than a direct identifier for re-identification purposes. Only 
someone possessing the key to the code can link the data to a particular participant.    
  De-Identified (all 18 HIPAA identifiers removed  
  Verified Statistically  
 
OR 
  Verified by Absence or Removal of 18 HIPAA identifiers   
  Limited Data Set 
  Other: Describe:        
 
4. Location of Data and/or Specimens, and Data Retention Plan:   
A. Data and/or Specimen Location: Data will be stored electronically in V06.med.va.gov\Dur\HSRD\V-
EXTRA_CVD_CIRB20-26 or on the VINCI servers workspace for the project.  Data that will be stored 
electronically include patient demographics, survey data, and audio/video data from recorded qualitative 
interviews or virtual support group sessions. The tracking database will be located behind the VA firewall on 
the R drive at the Durham VA. All surveys will be done using the currently approved version of the VA REDCap 
survey tool, which is hosted on the VINCI servers.  No study data will be stored on the hard drive of a PC.  
Paper records of data include signed informed consent forms, or surveys taken during outcome assessment 
visits and will be stored in locked file cabinets at each of the three sites.  
  Data will be also be placed at the VA Informatics and Computing Interface (VINCI; 
http://vaww.vinci.med.va.gov/vincicentral/VINCIWorkspace.aspx). The VA Informatics and Computing 
Infrastructure is a partnership between the VA Office of Information Technology and the Veterans’ Health 
Administration Office of Research and Development.  Researchers and operations staff can use VINCI to 

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access data and statistical analysis tools in a virtual working environment through a certified VHA network 
computer using the VA Intranet or Virtual Private Network (VPN).  
B. Data Retention Plan 
 Research records will be maintained and destroyed according to the National Archives and Records 
Administration, Records Schedule Number:  DAA-0015-2015-0004.  Records destruction, when authorized, will 
be accomplished using the then current requirements for the secure disposal of paper and electronic records.  
Currently, destruction of research records (see DAA-0015-2015-0004, section 7.6 “Research Investigator Files” 
for materials included in research records) is scheduled for 6 years after the cut-off (the cut-off is the 
completion of the research project) and may be retained longer if required by other federal agencies.  Records 
will not be destroyed without pre-notification to the facility records manager. .   
  Other data retention plan, describe:        
5. Data Access and Data Recipients:  Only members of our research team will have access to data.  The 
project coordinator, research assistants, interventionist, and statisticians will have access to identifiers and 
coded data.  This coded data can be shared with the co-investigators for analysis.  
 
All VA research personnel who have access to VHA records are instructed, in accordance with VA policy, on 
the requirements of Federal privacy and information laws and regulations, VA regulations and policies, and 
VHA policy. All study personnel who are VA employees working within the VA system have fulfilled all required 
HIPAA and other VA security and privacy policy training requirements and have agreed to follow guidelines 
pertaining to the protection of patient data. All research staff sign VA Rules of Behavior, and all study staff are 
up-to-date with VHA Privacy Policy Training and the VA Office of Cyber and Information Security Awareness 
Training Course. The data security and privacy procedures summarized in that course include logging off or 
locking the computer when walking away from it; no sharing of access codes, verify codes or passwords; not 
allowing anyone else to use the computer under one’s password; and disposing of sensitive information using 
VA-approved methods (e.g., shredder bins). 
Access to study data will be removed for all study personnel when they are no longer part of the research 
team.  
 
6. Data and/or Specimen Transportation and/or Transmission for all data and/or specimens involved 
in the study:   
 
  Data and/or specimens will not be transported or transmitted outside of each VA site  
 
   Data and/or specimens will be transmitted to other VA sites using the following method(s): 
A. Data 
  Data are de-identified and thus will be sent via unencrypted e-mail or unencrypted disk 
(encryption is optional). 
  Data are coded or contain identifiers and thus will be sent <choose method of transfer such as:  
PKI or RMS encrypted e-mail, FIPS 140-2 encrypted disk (with VA-authorized carrier and tracking), 
or FIPS 140-2 encrypted external drive (with VA-authorized carrier and tracking). You may identify a 
primary and secondary method>. 
  Other, describe:        

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B. Specimens 
  Specimens are de-identified and thus will be sent via standard carrier (tracking is optional).  
  Specimens are coded or contain identifiers and thus will be sent via VA-authorized carrier with 
tracking.   
  Other, describe:        
I. 
  Data and/or specimens will be transported to non-VA/VHA sites (e.g., academic affiliates, 
laboratories, etc.) using the following method(s): 
A. Data 
  Data are de-identified and thus will be sent via unencrypted e-mail or unencrypted CD. 
  Data are coded or contain identifiers and thus will be sent via <choose method of transfer such 
as FIPS 140-2 encrypted CD or FIPS 140-2 encrypted hard drive/flash drive> using VA—approved 
carrier with tracking.   
  Data are coded or identified and will be sent via the Safe Access File Exchange (SAFE) at 
https://safe.amrdec.army.mil/safe/.  SAFE is a secure method of exchanging files <2GB to and from 
individuals with a valid .gov, .mil, .com, or .edu email address. <insert information including 
collaborator name.> 
  Data are coded or identified and will be uploaded to sponsor website using electronic case 
report form (eCRF) <insert information including sponsor name and URL and the encryption the site 
uses.> 
 Other, describe:       
B. Specimens 
  Specimens are de-identified and thus will be sent via standard carrier (tracking is optional) or 
will be hand-delivered by research study personnel.  Specify method of delivery:        
  Specimens are coded and thus will be sent via VA-approved carrier with tracking or will be 
hand-delivered by research study personnel.  Specify method of delivery:        
 
In accordance with the HIPAA and the Privacy Act, for any coded or identifiable data or specimens released 
from the Durham VAMC (with the exception of Limited Data Sets), an Accounting of Disclosure (AOD) will be 
maintained (e.g., in a database or spreadsheet) that includes the participant’s name, date of the disclosure, 
description of the nature of the Individually Identifiable Information (III) disclosed, purpose of each disclosure, 
and the name and address of the person/agency to whom the disclosure was made. 
 
  We will communicate with veterans enrolled as participants in this research study through MyHealtheVet.    
 
 
 

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7.0 
Communication Plan 
 
 
There are four VA sites where research will occur.  All sites are considered engaged in this study: (1) 
Qualitative data collection and analyses will occur at Durham VAHCS. (2) Durham VAHCS staff will 
recruit, enroll, and consent patients for intervention and house the research data.  Statistical analyses 
will also occur at Durham.  (2) The Cleveland staff, overseen by Site-PI, will also recruit, enroll and 
consent patients and house research data.  The Baltimore staff, overseen by Site-PI, will also recruit, 
enroll and consent patients and house research data. The Atlanta staff, overseen by site-PI, will also 
recruit, enroll and consent patients and house research data. The VA Central IRB is the IRB of record 
for this study. 
The Site-PIs will ensure there is a Local Site Investigator (LSI) at each site from which patients are 
enrolled.  For this study, these sites include the Durham Healthcare System (with LSI and PI Hayden 
Bosworth, PHD) and Cleveland VAHCS. Baltimore VAHCS. After initial review, any revisions to the 
protocol, informed consent or HIPAA authorization will be submitted on Form 116 to the cIRB by the 
Durham VAHCS.  Once approved, the Durham PI will be responsible for forwarding the current 
documents to each of the other sites for immediate use.   
The site-PIs will communicate this information to other study staff via conference call, if needed. In 
addition, study PIs and LSI will be regularly updated through the weekly team meetings. 
Regular study meetings will occur with key members of the research team. Any issues that arise – 
related to IRB changes, adverse event reporting, data collection, or recruitment/enrollment concerns, 
can be shared among all sites and dealt with in a timely manner.  The project coordinator at the 
Durham site will be responsible for ensuring communication between all sites 
Data and Safety Monitoring 

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Because this is a minimal risk study involving only a telehealth-based intervention, we do not anticipate 
serious adverse events due to the study.  However, safety information will be monitored at each 
interaction with the patient by the Interventionist via telephone sessions and the Research Assistants at 
outcome visits.  All sites will be responsible for reporting SAEs to the PI in Durham as soon as the 
reporting individual becomes aware of the occurrence.  
SAEs identified in Durham will be reported to the Durham PI who is responsible for complying with all 
cIRB reporting requirements. SAEs identified in Baltimore and Cleveland and Atlanta will be reported to 
their respective site-PI who will report all SAEs to the Durham PI who will report to cIRB, as required.   
All adverse events will be reviewed by the Study PI, all four site-PIs (all of which are practicing MDs), 
the study statistician, and the project coordinator.  
Safety Reasons that trigger immediate suspension of research 
Participants should normally be withdrawn from the trial if a serious adverse event (SAE) occurs. 
Participants must be withdrawn from the trial if: 
a. They withdraw their consent 
b. Veteran subsequently meets one of the exclusion criteria for the study.  
c. The investigator considers it in the best interest of the veteran that he or she is withdrawn. 
d. Veteran displays abusive behavior towards staff 
e. Veteran is a female and become pregnant during the study 
f. The study is suspended or cancelled 
The reason and date of withdrawal will be documented by research staff in the study tracking database.  
For patients in the intervention arm who no longer want to participate in the intervention, they will still be 
eligible to complete the outcome assessments (at months 4, 8, 12) and receive payment for completion 
of those visits. 
The Durham PI will be responsible for reporting to the VA Central IRB within 5 business days any SAEs 
that meet the criteria, as well as any follow-up reports requested.  Summary information that did not 
require immediate reporting will be submitted at continuing review. 
The PI/SC will ensure adequate monitoring in the following ways: all study staff will have completed 
their required research training prior to beginning any research activity, ensuring that each member of 
the research team has a research scope of practice (SOP), updated annually, that clearly defines the 
duties in which the person is trained, qualified and allowed to perform for research purposes, and will 
maintain a staff listing of all personnel involved in the conduct of the study which will include their CITI 
and GCP training completion dates.   
All non-compliance with the study protocol will be reported.  Protocol deviations or protocol violations 
will be reported to the cIRB by the Durham PI within 5 business days after being made aware of the 
occurrence using Form 119 if initiated in response to an SAE or UAP, or Form 129 if the event was 
likely to have an adverse effect on the subjects rights, safety or welfare, their willingness to continue 
participation, or the integrity of the research data. 
 

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