A Phase 4, Open-label, Single Arm Study to Optimize Implementation of CABENUVA for the Treatment of HIV-1, for Administration in U.S. Community-based Infusion Centers or Other Alternate Sites of Administration
Phase: PHASE4
Conditions: HIV Infections
Sponsor: ViiV Healthcare

TMF-15719318 
CONFIDENTIAL 
ViiV Healthcare group of companies 
 
214747 
 
 
Protocol Amendment 06 
 
1 
 
TITLE PAGE 
Information Type: ViiV Healthcare Interventional Study Protocol 
Title: 
A Phase 4, open-label, single arm study to optimize 
implementation of CABENUVA for the treatment of HIV-1, 
for administration in U.S. community-based infusion centers or 
other alternate sites of administration 
Protocol Number: 
214747 / Amendment 06 
Compound 
Number: 
GSK1265744, CABENUVA 
Brief Title:  An implementation study using CABENUVA for the treatment of HIV-1, 
administered in infusion centers or other alternate sites of administration in the U.S. 
Development Phase 
Phase 4 
Acronym:  GLACIER - Giving Long Acting CABENUVA in an Infusion centER 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
US IND Sponsor Legal Registered Address:  
410 Blackwell Street,  
Durham, NC 27701 
Fax Number:  1 919 237 9294 
 
Marketing Authorisation Holder: 
ViiV Healthcare Company 
Regulatory Agency Identifying Number(s):   IND: 109,678 
Medical Monitor Name and Contact Information will be provided separately 
Sponsor Signatory: 
Sherene Shakib Min, MD, MPH 
VP, Head of Clinical Development 
ViiV Research & Development 
 
Approval Date:  29 Mar 2023 
Copyright 2023 ViiV Healthcare Company.  All rights reserved.  Unauthorized copying 
or use of this information is prohibited 

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PROTOCOL AMENDMENT SUMMARY OF CHANGE TABLE 
DOCUMENT HISTORY 
 
Document 
Date 
DNG Number 
Amendment 06 
29 Mar 2023 
TMF-15719318 
Amendment 05 
14 November 2022 
TMF-15061935 
Amendment 04 
6 October 2022 
TMF-15019036 
Amendment 03 
20 July 2022 
TMF-14758153 
Amendment 02 
16 March 2022 
TMF-14150714 
Amendment 01 
19 Nov 2021 
TMF-14150714 
Original Protocol 
11 April 2021 
2020N443730_00 
 
Amendment 01: Overall Rationale for Amendment 1 (See Annex 5: Protocol 
Amendments) 
Amendment 02: Overall Rationale for Amendment 02 (See Annex 5: Protocol 
Amendments) 
Amendment 03: Overall Rationale for Amendment 3 (See Annex 5: Protocol 
Amendments) 
Amendment 04: Overall Rationale for Amendment 4 (See Annex 5: Protocol 
Amendments) 
Amendment 05: Overall Rationale for Amendment 5 (See Annex 5: Protocol 
Amendments) 
Amendment 06: Overall Rationale for Amendment 6  
Section # and 
Name 
Description of Change 
Brief Rationale 
Global Change 
Added Alternate Sites of 
Administration (ASA) 
Add another type of site for 
CABENUVA administration 
Section 10.1: 
Clinical safety 
laboratory 
assessments 
Revised to state labs should 
be drawn prior to the first 
study injections. 
If an IC/ASA will have labs 
drawn off-site, added clarity 
on when the labs should be 
drawn prior to 
Baseline/Month 1 Visit 
Added clarity to the SOA 
regarding the collection of labs 
prior to the Baseline/Month 1 
Visit 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Annex 1: 
Schedule of 
Activities 
Added link to Section 10.1 
for Baseline/Month lab 
assessments 
Clarity  
Annex 5.1: 
Protocol 
Amendments 
Moved the Table of Changes 
from Protocol Amendment 
05 to Annex 5.1  
Moved according to the Protocol 
template 
 
 

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TABLE OF CONTENTS 
PAGE 
1. 
ABSTRACT .............................................................................................................. 8 
2. 
BACKGROUND AND RATIONALE ........................................................................ 11 
2.1. 
Background ................................................................................................ 11 
2.2. 
Rationale .................................................................................................... 11 
2.3. 
Benefit/Risk Assessment ............................................................................ 12 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 13 
4. 
RESEARCH DESIGN ............................................................................................. 19 
4.1. 
Study Design .............................................................................................. 19 
4.2. 
Study Population ......................................................................................... 21 
4.2.1. 
Eligibility Criteria .......................................................................... 21 
4.3. 
Study Groups and Duration ........................................................................ 22 
4.3.1. 
Participants with HIV-1 ................................................................. 22 
4.3.2. 
HIV Care Providers ...................................................................... 23 
4.3.3. 
Infusion Center Staff .................................................................... 24 
5. 
IMPLEMENTATION RESEARCH METHODS ........................................................ 25 
5.1. 
Formative Evaluation Procedures ............................................................... 25 
5.1.1. 
Expert Panel ................................................................................ 25 
5.1.2. 
Implementation Assessments ...................................................... 26 
5.1.3. 
Timepoint Definitions for Completion of Questionnaires 
and Interviews ............................................................................. 29 
5.1.4. 
Primary Endpoint ......................................................................... 30 
5.1.5. 
Blueprint and Plan of Treatment .................................................. 30 
5.1.6. 
Scale-up ...................................................................................... 31 
5.2. 
Scientific Rationale for Study Design and Research Methods ..................... 32 
5.2.1. 
Implementation Frameworks ........................................................ 32 
6. 
STATISTICAL CONSIDERATIONS ........................................................................ 33 
6.1. 
Study Size .................................................................................................. 34 
6.2. 
Essential Analysis ....................................................................................... 37 
6.3. 
Secondary Analysis .................................................................................... 39 
6.4. 
Other/Tertiary Endpoints ............................................................................. 40 
6.5. 
Limitations of the Research Methods .......................................................... 41 
7. 
PROTECTION OF HUMAN SUBJECTS ................................................................ 41 
7.1. 
Ethical Approval and Participant Consent ................................................... 41 
7.2. 
Participant Confidentiality ........................................................................... 41 
7.3. 
Informed Consent Process ......................................................................... 42 
7.4. 
Quality Control / Study Monitoring .............................................................. 42 
8. 
CABENUVA AND CONCOMITANT THERAPY ...................................................... 43 
8.1. 
Missed CANENUVA Injections .................................................................... 43 
8.2. 
Treatment of an Overdose .......................................................................... 43 
8.3. 
Concomitant Therapy.................................................................................. 44 

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9. 
DISCONTINUATION OF CABENUVA AND PARTICIPANT 
DISCONTINUATIONS ............................................................................................ 44 
9.1. 
Discontinuation of CABENUVA ................................................................... 44 
9.2. 
Temporary Discontinuation ......................................................................... 45 
9.3. 
Participant Discontinuation / Withdrawal from the Study ............................. 45 
9.4. 
Lost to Follow-up ........................................................................................ 45 
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS AND SAFETY 
ASSESSMENTS .................................................................................................... 46 
10.1. 
Clinical safety laboratory assessments ....................................................... 46 
10.2. 
Liver Chemistry Monitoring ......................................................................... 47 
10.3. 
Adverse Events (AEs), Pregnancy Exposure and Incident Reporting .......... 47 
10.3.1. 
Specific Adverse Events to be Documented in this Study ............ 48 
10.3.2. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 49 
10.3.3. 
Methods of Detecting AEs and SAEs ........................................... 49 
10.3.4. 
Follow-up of AEs and SAEs ......................................................... 49 
10.3.5. 
Regulatory Reporting Requirements for SAEs ............................. 49 
10.3.6. 
Adverse Event Follow-up with the HIV Care Provider .................. 50 
10.3.7. 
Causality Assessments ................................................................ 50 
10.3.8. 
Serious Post-Injection Reactions ................................................. 51 
10.3.9. 
Injection Site Reactions ............................................................... 51 
10.3.10. Reporting of AEs and Timelines ................................................... 52 
10.3.11. Pregnancy ................................................................................... 53 
10.3.12. Cardiovascular and Death Events ................................................ 54 
10.3.13. Medical Device Deficiency ........................................................... 55 
11. REFERENCES ....................................................................................................... 56 
ANNEX 1: SCHEDULE OF ACTIVITIES ....................................................................... 58 
ANNEX 2. LIST OF STAND-ALONE DOCUMENTS ...................................................... 65 
ANNEX 3: AE AND SAE DEFINITIONS ........................................................................ 66 
Annex 3.1   Definition of an Adverse Event ............................................................ 66 
Annex 3.2   Definition of an SAE ............................................................................ 67 
Annex 3.3   Definition of a Cardiovascular Event .................................................... 69 
Annex 3.4   Recording and Follow-up of AEs and SAEs ......................................... 69 
Annex 3.5   Reporting of SAEs to ViiV/GSK ........................................................... 71 
ANNEX 4: CONTACT INFORMATION FOR REPORTING OF AES AND SAES 
AND PREGNANCIES ............................................................................................. 73 
ANNEX 5: PROTOCOL AMENDMENTS ....................................................................... 74 
Annex 5.1  Protocol Amendment 05 (14 November 2022 ....................................... 74 
Annex 5.2  Protocol Amendment 04 (6 October 2022) ........................................... 74 
Annex 5.3  Protocol Amendment 03 (20July2022) .................................................. 76 
Annex 5.4   Protocol Amendment 02 (16 March 2022) ........................................... 79 
Annex 5.5  Protocol Amendment 01 (19 November 2021) ...................................... 82 
 
 

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LIST OF ABBREVIATIONS  
ADRs 
Adverse drug reactions 
AE 
Adverse event 
AIF 
Alternate Injection Facility 
AIM 
Acceptability of Intervention Measure 
ALT 
Alanine aminotransferase 
APR 
Antiretroviral Pregnancy Registry  
ARV 
Antiretroviral Products 
ASA 
Alternate Site of Administration 
AST 
Aspartate aminotransferase 
BMI 
Body Mass Index 
c/mL 
Copies/milliliter 
CABENUVA 
Cabotegravir LA plus rilpivirine LA 
CFIR 
Consolidated Framework for Implementation Research 
CI 
Confidence Interval 
CRO 
Clinical research organization 
CSR 
Clinical study report 
DAIDS 
Division of acquired immune deficiency syndrome 
DBR 
Database release 
DDI 
Drug-Drug Interaction 
ECG 
Electrocardiogram 
EDURANT 
Rilpivirine 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
FIM 
Feasibility of Intervention Measure 
FPFV 
First participant first visit 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HCP 
Healthcare Provider 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
IC 
Infusion Center 
ICH 
International Conference on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ICF 
Informed Consent Form  
IM 
Intramuscular 
IRB 
Institutional Review Board 
ISR 
Injection Site Reaction 
LAR 
Legally Authorized Representative 
LMP 
Last Menses Period  
LPFV 
Last participant first visit 
M 
Month 
MedDRA 
Medical Dictionary for Regulatory Activities 
PLWHIV 
People Living with HIV 
POCBP 
Participants of Child-bearing potential 

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POT 
Plan of Treatment 
PPD 
Pharmaceutical Product Development Inc 
PVG 
Pharmacovigilance 
Q1 
Quarter 1 
Q4 
Quarter 4 
QTc 
Corrected QT interval  
QUERI 
Quality Enhancement Research Initiative 
REP 
Replicating Effective Programs 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SoA 
Schedule of Activities 
SRM 
Study Reference Manual 
SUSAR 
Suspected unexpected serious adverse reactions 
US 
United States 
USPI 
United States Prescribing Information 
VHC 
ViiV Healthcare 
VOCABRIA 
Cabotegravir 
WHO 
World Health Organization 
 
 
 
Trademark Information 
Trademarks of ViiV Healthcare  
 
Trademarks not owned by ViiV 
Healthcare 
CABENUVA 
 
EDURANT 
VOCABRIA 
 
 
 
 
 
 
 
 

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1. 
ABSTRACT 
Background/Rationale:  CABENUVA is a 2-drug co-packaged product of cabotegravir 
plus rilpivirine, both administered as long-acting (LA) intramuscular (IM) once-monthly 
or every 2-monthly injections is a newly approved treatment for human 
immunodeficiency virus (HIV).  Clinical trial results have shown that CABENUVA 
administered either once monthly or once  every 2-months is non-inferior to the daily oral 
treatment for HIV. 
CABENUVA treatment will require a paradigm shift in how HIV care is delivered, 
especially in the United States (US).  People living with HIV (PLWHIV) will no longer 
be able to only see their providers one to two times a year for a prescription refill and 
monitoring visit but will instead attend appointments for their injections once a month.  
As a result, implementation of CABENUVA in HIV clinical settings in the U.S. poses 
new health delivery challenges and may require a shift in resources and openness to new 
ways of delivering and receiving treatment.  Expanding where the treatment can be 
administered, using alternative injection facilities, such as infusion centers (IC) or other 
alternate sites of administration (ASA), has the potential to address workload capacity 
with this paradigm shift, and may positively impact treatment engagement and retention 
for PLWHIV.  ICs/ASAs are an appealing option that will help ease the burden of 
additional appointments, administrative work, and drug ordering in HIV specialty clinics 
and provide PLWHIV greater flexibility in where they receive their monthly or every 2-
month injections. 
In this study, the intervention is the process of using an infusion center as the location to 
receive the CABENUVA IM injections.  The acceptability and feasibility of the IC/ASAs 
to deliver CABENUVA IM injections, will be assessed from the perspectives of the 
participants, HIV care providers (which could potentially include other Provider clinical 
staff) and IC/ASA staff.  The main objective of this post-approval study is to develop, 
evaluate and scale-up an implementation blueprint for IM administration of CABENUVA 
for HIV-1 treatment at ICs/ASAs. 
Study Design:  This is a Phase 4, single arm, open-label, multi-center study examining 
the administration of CABENUVA IM in infusion centers (ICs) or alternate sites of 
administration (ASA) in the United States.  Additional Infusion Centers (ICs) or ASAs 
(initiating approximately between November 2022 to Q2 2023) will increase the 
geographical area in the US and to scale-up of the implementation blueprint.   
Participants enrolled in the study will receive commercially available CABENUVA via 
prescription from their HIV care provider.  Participants will be monitored according to 
usual standard care at their physician’s discretion.  No more than 120 participants will be 
recruited.  CABENUVA injections will be administered at the ICs/ASAs for 8 months. 
The study has two main components.  The first component is to conduct a formative 
evaluation of the feasibility and acceptability of the IC/ASA model by participants, 
IC/ASA staff and HIV providers and the development of the implementation blueprint.  
The second component involves a scale-up of the optimized implementation blueprint 
across all ICs/ASAs in this study.   

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An Expert Panel will meet to generate an implementation blueprint to guide successful 
implementation prior to the first participant first visit (FPFV).  The blueprint will be 
optimized over the first 6 months and will be used as a foundation for the enrolment of 
the remaining participants.  As the Expert Panel will complete their assessments 
Q4 2022, following this timepoint, key IC/ASA staff members involved in decision 
making and/or overseeing daily operations at the IC/ASA, will be given the opportunity 
to review and revise both the optimized blueprint and the POT.  The blueprint and POT 
will be reviewed and/or revised as necessary pre-study, at 3-4 months into the study to 
ensure experience with participants, and at the end of study.   
Some HIV care providers manage their patients in conjunction with other clinic staff 
members who work with the ICs/ASAs and may be better to complete some study 
assessments.  Thus, in Protocol Amendment 4, the completion of study questionnaires 
and potential interviews to be completed by the HIV Care Providers could potentially be 
completed by other clinical staff members.  
• Note: the potential for other clinical staff to complete HIV Care Provider 
questionnaires and potential interviews, will hereafter be represented by HIV Care 
Providers/clinical staff. 
Objectives: The primary objective is to evaluate the feasibility of CABENUVA 
administration at infusion centers from participants.   
Secondary objectives include: 
• To evaluate feasibility of CABENUVA administration at infusion centers from 
HIV care providers/clinical staff and IC/ASA staff 
• To evaluate feasibility of the process of administering CABENUVA at the 
infusion center 
• To evaluate acceptability of CABENUVA administration at infusion centers from 
HIV care providers/clinical staff, participants, and IC/ASA staff 
• To evaluate feasibility, acceptability and the process of CABENUVA 
administration at infusion centers from the Expert Panel 
• To evaluate perceptions, facilitators, and barriers/concerns by HIV care 
providers/clinical staff, participants, and IC/ASA staff  
• To assess the preference of participants on the location to receive CABENUVA 
• To assess the advantages to receive or refer participants to receive CABENUVA 
at the infusion center from participants and HIV care providers/clinical staff 
• To assess the disadvantages about receiving CABENUVA at the infusion center 
from participants and HIV care providers/clinical staff 
• To evaluate the acceptability of receiving and referring participants for 
CABENUVA injections at infusion centers from participants and HIV care 
providers/clinical staff 

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• To evaluate the usefulness of blueprint intervention by IC/ASA staff and the Plan 
of Treatment (POT) for HIV care providers/clinical staff 
• To evaluate overall opinion of receiving and administering the injection at an 
infusion center by IC/ASA staff, participants and HIV care providers/clinical staff 
• To evaluate fidelity to treatment and dosing window 
Analysis Methods:  Implementation science methodology will be used in this study to 
assess the acceptability and feasibility of an IC/ASA for the delivery of CABENUVA IM 
injections.  This study will evaluate the acceptability and feasibility of our 
implementation strategy using the Feasibility of Intervention Measure (FIM) and the 
Acceptability of Intervention Measure (AIM).   
In addition to the FIM and AIM, other quantitative questionnaires will be included to 
address additional constructs related to the study objectives.  These questions will cover 
constructs related to perceptions, facilitators, barriers, usefulness of the blueprint 
advantages, disadvantages, and processes related to CABENUVA administration at 
ICs/ASAs.  These additional quantitative questionnaires will measure endpoints that are 
not directly captured by the AIM and FIM. 
The primary endpoint in terms of feasibility is the percentage of participants that agree or 
completely agree (a score of 4 or higher) across all items on the FIM at Month 8.  For 
FIM of participants, HIV care providers/clinical staff and IC/ASA staff at each specified 
timepoint, the sample percentage and associated 95% confidence interval will be 
presented.   
In addition to summary of FIM scores of participants at different timepoints, the change 
in FIM scores of each item will be analysed, and the shift table for each item of FIM will 
be given to display the number of participants who completely disagree (scale=1), 
disagree (scale=2), neither agree or disagree (scale=3), agree (scale=4), completely agree 
(scale=5) at Baseline/Month 1 and the shift of these quantities at each timepoint that 
follows.   
The feasibility composite score will be further refined based on the standard process 
outlined in the blueprint.  The exact components of feasibility composite score will be 
informed by the Expert Panel process to ensure it matches the critical variables identified 
by all members of the panel. 
Subgroup analysis will be performed to evaluate the effect of contextual factors on the 
variability of responses to feasibility.  These factors include, but not limited to, 
demographic, baseline characteristics, prior clinical experience, initiation method (oral 
lead in or direct to injection or receiving continuation dose), the number of injections 
received prior to enrollment and injection option (monthly or every 2-months) for 
participants, provider type, site type and setting (urban, suburban, rural) for IC/ASA staff, 
and affiliation for HIV care providers/clinical staff.  
The analysis methods for the secondary endpoints of acceptability, and fidelity will be 
similar to that of the feasibility endpoints. 

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2. 
BACKGROUND AND RATIONALE 
2.1. 
Background 
CABENUVA is a 2-drug co-packaged product of cabotegravir plus rilpivirine, both 
administered as long-acting (LA) intramuscular (IM) injections, is a newly approved 
treatment for human immunodeficiency virus (HIV).  Clinical trial results have shown 
that CABENUVA administered once monthly and once every 2-months is non-inferior to 
the daily oral treatment for HIV [Margolis, 2017; Swindells, 2020; Orkin, 2020; Overton, 
2020].  Forty-seven percent of healthcare provides (HCPs) believed that “some” patients 
(25–50%) would be appropriate while nearly one-quarter of HCPs (23%) felt that “many” 
patients (more than 50%) would be appropriate candidates for LA antiretroviral therapy 
(ART) [Murray, 2020].  This treatment will require a paradigm shift in how HIV care is 
delivered, especially in the United States (US).  People living with HIV (PLWHIV) will 
no longer be able to only see their providers one to two times a year for a prescription 
refill and monitoring visit but will instead attend appointments for their injections once a 
month or once every 2 months.  As a result, implementation of CABENUVA in HIV 
clinical settings in the U.S. poses new health delivery challenges and may require a shift 
in resources and openness to new ways of delivering and receiving treatment.  Expanding 
where the treatment can be administered, using alternative injection facilities (AIFs), 
ICs/ASAs has the potential to address workload capacity with this paradigm shift, and 
may positively impact treatment engagement and retention for PLWHIV. 
ICs/ASAs are an appealing option that will help ease the burden of additional 
appointments, administrative work, and drug ordering in HIV specialty clinics and 
provide PLWHIV greater flexibility in where they receive their monthly or every 2-
month injections.  These facilities have an existing infrastructure that supports a wide 
range of treatments and can likely be adopted for administration of CABENUVA.  
Infusion centers exist across the US and have an informal network of sharing information 
both within the same company of infusion centers, as well as across companies.   
Now that CABENUVA is commercially available in the United States, rapidly addressing 
needs to scale-up availability of the treatment will be important to ensure that those who 
want the treatment have access to it in a way that works for them and their providers.  
AIFs, like infusion centers, are a natural option for administering CABENUVA, as they 
routinely administer injectable treatments to a diverse patient population, have trained 
medical staff onsite, and have existing infrastructure to ensure communication between 
the IC/ASA, PLWHIV, and HIV providers.  Additionally, these centers are not diagnosis 
specific, which allows for an added level of privacy during treatment appointments.  
Generating and testing acceptability and feasibility of an implementation blueprint to 
understand how this might work in routine care post-approval is an important next step to 
ensure that implementation of CABENUVA at infusion centers provides optimal care and 
experience for HIV care providers/clinical staff, PLWHIV, and infusion center staff. 
2.2. 
Rationale 
This post-approval, Phase 4 study will use an Expert Panel consisting of selected HIV 
care providers that may refer their PLWHIV to an IC/ASA, key IC/ASA staff members 

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involved in decision making and/or oversight of daily operations and ViiV Healthcare 
(VHC) to collaboratively develop an implementation blueprint and a plan of treatment 
(POT) to establish best practices and standard operating procedures for the administration 
of CABENUVA at ICs/ASAs (see Section 5.1 for full descriptions of the blueprint and 
POT).  The blueprint will be used to guide the development and/or refinement of the POT 
which will be reviewed prior to the HIV care provider’s first patient with HIV-1 enrolled 
in the study at the IC/ASA.   
Implementation science methodology will be used to assess the acceptability and 
feasibility of an IC/ASA for the delivery of CABENUVA IM injections.  In this study, 
the intervention is the process of using an infusion center as the location to receive the 
CABENUVA IM injections.  The acceptability and feasibility of the IC/ASA to deliver 
CABENUVA IM injections, will be assessed from the perspectives of the participants, 
HIV care providers/clinical staff and IC/ASA staff.   
The intention of this post-approval study is to develop, evaluate and scale-up an 
implementation blueprint for IM administration of CABENUVA for HIV-1 treatment at 
ICs/ASAs.  The study has two main components.  The first component is to conduct a 
formative evaluation of the feasibility and acceptability of the IC/ASA model by 
participants, IC/ASA staff and HIV providers and the development of the implementation 
blueprint.  The second component involves a scale-up of the implementation blueprint 
across all ICs/ASAs in this study.   
An Expert Panel will meet to generate an implementation blueprint to guide successful 
implementation prior to the first participant first visit (FPFV).  The blueprint will be 
optimized over the first 6 months and will be used as a foundation for the enrolment of 
the remaining participants.  The Expert Panel will complete all assessments in Q4 2022.  
The optimized blueprint will be reviewed and potentially revised by key IC/ASA staff 
members involved in decision making and overseeing daily operations at the IC/ASA. 
Participants enrolled in the study will receive commercially available CABENUVA via 
prescription from their HIV care provider.  Participants will be monitored according to 
usual standard care at their physician’s discretion. 
As a result, this study will examine the impact of the implementation blueprint and POT 
in enhancing the uptake of infusion centers by HIV care providers/clinical staff and 
patients with HIV-1 as the location they use to provide CABENUVA IM injections for 
their PLWHIV.  
2.3. 
Benefit/Risk Assessment 
Refer to the most recent USPI CABENUVA USPI for more detailed information about 
the known and expected benefits and risks and reasonably expected adverse events (AEs) 
of CABENUVA CABENUVA USPI. 

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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To evaluate feasibility of CABENUVA 
administration at infusion centers from 
participants  
• Proportion of participants that agree or 
completely agree (a score of 4 or higher) 
across all items on the FIM at Month 8 
Secondary  
To evaluate feasibility of CABENUVA 
administration at infusion centers from 
participants, HIV care providers/clinical staff 
and IC/ASA staff 
• Proportion of participants that agree or 
completely agree (a score of 4 or higher) 
across all items on the FIM at Month 1, 
Month 3 
• Proportion of HIV care providers/clinical 
staff that agree or completely agree (a 
score of 4 or higher) across all items on 
the FIM at Month 1, Month 4 and at 
Month 8 
• Proportion of IC/ASA Staff that agree or 
completely agree (a score of 4 or higher) 
across all items on the FIM prior to Month 
1, at Month 3, and Month 8 
• Change over time in the FIM at Month 3 
and Month 8 with participants 
• Change over time in the FIM at Month 4 
and Month 8 with HIV care 
providers/clinical staff 
• Change over time in the FIM at Month 3, 
and Month 8 with IC/ASA staff 
• Summary of other quantitative 
questionnaires assessed with participants 
at Month 1, Month 3, and Month 8 
• Summary of other quantitative 
questionnaires assessed with HIV care 
providers/clinical staff at Month 1, Month 4 
and Month 8 
• Summary of other quantitative 
questionnaires assessed with IC/ASA staff 
prior to Month 1, at Month 3, and at Month 
8 

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Objectives 
Endpoints 
• Qualitative interviews assessed at Month 8 
with participants, HIV care 
providers/clinical staff and IC/ASA staff 
To evaluate feasibility of the process of 
administering CABENUVA at the infusion 
center 
• Summary of composite score of the 
feasibility process indications through 
Month 8  
• Change over time through Month 8 in the 
composite score and each item of 
composite score. 
To evaluate acceptability of CABENUVA 
administration at infusion centers from HIV 
care providers/clinical staff, participants, and 
IC/ASA staff 
• Proportion of HIV care providers/clinical 
staff that agree or completely agree (a 
score of 4 or higher) across all items on 
the AIM at Month 1, Month 4 and Month 8 
• Proportion of participants that agree or 
completely agree (a score of 4 or higher) 
across all items on the AIM at Month 1, 
Month 3and Month 8 
• Proportion of IC/ASA staff that agree or 
completely agree (a score of 4 or higher) 
across all items on the AIM prior to 
Month 1, at Month 3, and Month 8 
• Change of HIV care providers/clinical staff 
over time in the AIM at Month 4 and Month 
8 
• Change of participants and IC/ASA staff 
respectively over time in the AIM at 
Month 3, and Month 8 
• Summary of other quantitative 
questionnaires assessed with HIV care 
providers/clinical staff at Month 1, Month 4 
and Month 8 
• Summary of other quantitative 
questionnaires assessed at Month 1, 
Month 3, and Month 8 with participants  
• Summary of other quantitative 
questionnaires assessed prior to Month 1, 
at Month 3 and Month 8 with IC/ASA staff 
• Qualitative interviews assessed at Month 8 
with participants, HIV care 

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Objectives 
Endpoints 
providers/clinical staff and IC/ASA staff 
To evaluate feasibility, acceptability and the 
process of CABENUVA administration at 
infusion centers from the Expert Panel 
• Proportion of Expert Panel that agree or 
completely agree (a score of 4 or higher) 
across all items on the FIM and AIM 
respectively prior to FPFV, and at Month 3 
and Month 6 
• Change of Expert Panel over time in FIM 
and AIM respectively through Month 6 
• Summary of other quantitative 
questionnaires assessed with Expert Panel 
prior to FPFV, and at Month 3 and Month 6 
• Qualitative interviews assessed with 
Expert Panel prior to FPFV and at Month 6  
To evaluate perceptions, facilitators, and 
barriers/concerns by participants, HIV care 
providers/clinical staff, and IC/ASA staff 
• Summary of participant other quantitative 
questionnaires at Month 1, Month 3 and 
Month 8 
• Summary of IC/ASA staff other 
quantitative questionnaires prior to Month 
1, at Month 3, and Month 8 
• Summary of HIV care provider/clinical staff 
other quantitative questionnaires at 
Month 1, Month 4, and Month 8  
• Qualitative interviews assessed at Month 8 
with HIV care providers/clinical staff, 
participants and IC/ASA staff 
To assess the preference of participants on 
the location to receive CABENUVA 
• Summary of preference on the location to 
receive CABENUVA at Month 1, Month 3, 
and Month 8 assessed by participant other 
quantitative questionnaires  
• Qualitative interviews assessed at Month 8 
with participants  
To assess the advantages to receive or refer 
participants to receive CABENUVA at the 
infusion center from participants and HIV care 
providers/clinical staff 
• Summary of advantages of receiving 
CABENUVA at IC/ASA at Month 1, Month 
3, and Month 8 assessed by participant 
other quantitative questionnaires  
• Summary of advantage to referring 

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Objectives 
Endpoints 
participants to the IC/ASA to receive 
CABENUVA at Month 1, Month 4, and 
Month 8 assessed by HIV care 
provider/clinical staff other quantitative 
questionnaires 
• Qualitative interviews assessed at Month 8 
with participants and HIV care 
providers/clinical staff  
To assess the disadvantages about receiving 
CABENUVA at the infusion center from 
participants and HIV care providers/clinical 
staff 
• Summary of disadvantages of receiving 
CABENUVA at ICs/ASAs from participant 
other quantitative questionnaires at Month 
1, Month 3, and Month 8  
• Summary of disadvantage of referring 
participants to IC/ASA for CABENUVA 
injections from HIV care providers/clinical 
staff other quantitative questionnaires at 
Month 1, Month 4 and Month 8 
• Qualitative interviews assessed at Month 8 
with participants and HIV care 
providers/clinical staff 
To evaluate the acceptability of receiving and 
referring participants for CABENUVA injections 
at infusion centers from participants and HIV 
care providers/clinical staff 
• Summary of acceptability of the process of 
receiving injections at ICs/ASAs from 
participant other quantitative 
questionnaires at Month 1, Month 3 and 
Month 8 
• Summary of acceptability of the process of 
referring participants to the infusion center 
for CABENUVA by HIV care 
providers/clinical staff other quantitative 
questionnaires at Month 1, Month 4, and 
Month 8 
• Qualitative interviews assessed at Month 8 
with participants and HIV care providers 
To evaluate the usefulness of blueprint 
intervention by IC/ASA staff and the POT for 
HIV care providers/clinical staff 
• Summary of usefulness of the blueprint 
intervention by IC/ASA staff other 
quantitative questionnaires prior to Month 
1, at Month 3 and Month 8 

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Objectives 
Endpoints 
• Summary of usefulness of the POT by HIV 
care providers/clinical staff other 
quantitative questionnaires at Month 4 and 
Month 8  
• Qualitative interviews assessed at Month 8 
with HIV care providers/clinical staff and 
IC/ASA staff 
To evaluate overall opinion of receiving and 
administering the injection at an infusion 
center by IC/ASA staff, participants and HIV 
care providers/clinical staff 
• Summary of the overall opinion of 
administering the injection at an IC/ASA by 
IC/ASA staff other quantitative 
questionnaires prior to Month 1, at 
Month 3, and Month 8 
• Summary of overall opinion of receiving 
CABENUVA at an infusion center by 
participant other quantitative 
questionnaires at Month 1, Month 3, and 
Month 8. 
• Summary of overall opinion of referring 
patients to an IC/ASA center for 
CABENUVA injections by HIV care 
provider/clinical staff via other quantitative 
questionnaires at Month 1, Month 4 and 
Month 8 
• Qualitative interviews at Month 8 with 
participants, HIV care providers/clinical 
staff and IC/ASA staff  
To evaluate fidelity to treatment and dosing 
window 
• Proportion of injections occurring within 
target window from target date ( 7 days 
of target date) through Month 8 
Other / Tertiary 
CCI

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Objectives 
Endpoints 
 
 
 
CCI

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4. 
RESEARCH DESIGN  
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
4.1. 
Study Design 
This is a Phase 4, single arm, open-label, multi-center study examining the administration 
of CABENUVA IM in infusion centers in the United States.  This study is being 
conducted following FDA approval and commercial availability of CABENUVA in the 
U.S.   
Eligible and consenting participants will be followed for 8 months to evaluate and scale-
up an implementation blueprint for IM administration of CABENUVA for HIV-1 
treatment at ICs/ASAs.  The total study duration for participants is approximately 8 
months from the time of enrollment and receipt of the first study related administration of 
CABENUVA IM injections at the IC/ASA.  For a detailed Schedule of Activities (SoA) 
refer to Annex 1: Schedule of Activities.  CABENUVA dosing adherence information 
and schematics can be found in the Study Reference Manual (SRM). 
 
 

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Figure 1 
Study Design Schematic 
 
 
Expert Panel questionnaires completed prior to the first participants first visit at the Month 1 visit.  The Expert Panel will 
complete their review and optimization of the blueprint in Q4 2022.  Thus, the ICs/ASAs initiating between approximately 
from November 2022 and Q1 2023 will use the optimized version of the blueprint and key IC/ASA staff will be allowed to 
modify prior to site enrollment, at 3-4 months and at the Month 8 visit. 
Questionnaires include the FIM, AIM and other quantitative questionnaires 
Participant assessments are completed based on Month regardless of monthly versus every-2-month dosing  
Note,  Study design may not include all potential patterns of dosing.  Talk to the HIV Care Provider or the Medical 
Monitor if you have any questions on the injection schedule. 
 

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4.2. 
Study Population 
During the recruitment period, the aim is to recruit no more than 120 participants who 
have been prescribed CABENUVA by their HIV care provider.  
After signing an informed consent, participants will complete Baseline's assessments to 
confirm participant eligibility.  Each participant being screened for study enrolment 
evaluation will be assigned a participant number at the Baseline visit.   
4.2.1. 
Eligibility Criteria 
4.2.1.1. 
Inclusion Criteria 
AGE:  
1 
Adults (18 years old) at the time of signing the informed consent. 
Type of Participant and Disease Characteristics 
2 
 HIV-1 infected and have been prescribed CABNEUVA per the USPI.  Participants 
can be enrolled:  
• If they have been taking oral VOCABRIA + EDURANT or other ART for 
approximately 1 month (at least 28 days) prior to Baseline/Month 1, or 
• Already taking CABENUVA prior to Baseline/Month 1 and the last injections 
were within a 1 month  7-day window or for every 2-month injections, the 
timing will vary they are receiving the initiation injections (1 month  7-day) or 
the continuation injections (2 months  7 days) per the USPI, or 
• Prescribed direct to inject and receive their 1st injection without an oral lead in at 
the Infusion Center on the last day of any other antiretroviral therapy.  
Informed Consent 
3 
Capable of giving signed informed consent as described in Section 7.3 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
Other 
4 
Agreement to receive CABENUVA IM injections at participating infusion center.   
4.2.1.2. 
Exclusion Criteria 
Participants may be excluded from the study, in consultation with the HIV care 
provider, based on information from the most current Prescribing Information 
[CABENUVA USPI] at the time of study enrolment. 
1. Contraindications, as per the current Prescribing Information [CABENUVA USPI]  
• Previous hypersensitivity reaction to cabotegravir or rilpivirine.  
• Contraindicated co-administered drugs: 

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o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, 
phenytoin 
o Antimycobacterials: Rifabutin, rifampin, rifapentine 
o Glucocorticoid (systemic): Dexamethasone (more than a single-dose 
treatment) 
o Herbal product: St John’s wort (Hypericum perforatum) 
2. New health condition / prohibited medication reported 
• After discussion with the referring HIV care provider a decision was made not to 
enter participant into the study 
3. Other Reason at the discretion of the HIV care provider or IC/ASA staff 
4.3. 
Study Groups and Duration 
This study will include the following groups: An Expert Panel, HIV care providers, 
virologically suppressed PLWHIV seeking to start or continue CABENUVA for 
treatment for HIV-1, and the IC/ASA staff.  A CABENUVA POT will be agreed between 
the HIV care provider and the IC/ASA prior to study participants receiving their first 
study related injections at the IC/ASA. 
Assessments can be found in Annex 1: Schedule of Activities and in the POT.   
4.3.1. 
Participants with HIV-1 
PLWHIV are allowed in the study if they have been prescribed CABENUVA per the 
USPI [CABENUVA USPI] and meet all eligibility criteria (Section 4.2.1) at the 
Baseline/Month 1 visit.  Participants meeting all eligibility criteria will sign the informed 
consent form at the IC/ASA and will enter into the study.   
If a participant plans to miss the injections by more than 7 days, in consultation with the 
HIV care provider, oral VOCABRIA + EDURANT or other ART regimens should be 
taken daily to replace up to 2 consecutive planned missed monthly injection visits or 
every 2-month injection visit-doses.  Dosing of oral bridging in the event of missed doses 
will be in accordance with the most recent CABENUVA prescribing information 
[CABENUVA USPI]. 
In consultation with the HIV care provider, participants may switch from monthly 
injections to an every-2-month continuation injection schedule, or from a 2-month 
continuation injection schedule to a monthly continuation dosing schedule.  When 
switching dosing regimens, follow all instructions as outlined in the most current 
Prescribing Information [CABENUVA USPI].  The total duration of study participants is 
approximately 8 months from the time of enrolment. and receipt of the first study related 
administration of CABENUVA IM injections at the IC/ASA.  A participant is considered 
to have completed the study if he/she has finished all Month 8 assessments. 

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4.3.2. 
HIV Care Providers  
Selected HIV care providers will be included on the Expert Panel.  The Expert Panel will 
meet prior to Baseline/Month 1, and as required over the first 6 months, and per the SoA 
(Annex 1: Schedule of Activities) to develop the CABENUVA implementation blueprint 
as described in Section 5.1.  The Expert Panel will complete the Month 6 review and 
revision of the blueprint within 2 to 4 weeks of the last site initiation visits of the 
additional ICs/ASAs.   
Any HIV care provider will be allowed to refer PLWHIV to approximately 35 designated 
ICs/ASAs.  Once an HIV care provider has identified a PLWHIV who would benefit 
from receiving CABENUVA or is already receiving CABENUVA and the patient agrees 
to receive the CABENUVA IM injections given at the IC/ASA, the provider will send a 
referral to the IC/ASA.  The IC/ASA will conduct insurance verification.  Once insurance 
verification is approved and reviewed with the patient, the IC/ASA will inform the HIV 
care provider and the patient will initiate treatment per the CABENUVA USPI. 
HIV care providers will manage all medical and clinical aspects of their PLWHIV during 
the study including management of adverse events.  The HIV care provider can request 
the following procedures to take place at the IC/ASA (i.e., local labs, vital signs) at any 
time. 
• Prior to their HIV care providers first participant first visit (FPFV), providers will 
work with the IC/ASA to review and complete the POT for their patients.  The 
HIV care provider will be notified that IC/ASA staff, clinical research 
organization (CRO) staff and/or the Medical Monitor may request additional 
information, including medical records if required, on CABENUVA-related AEs, 
AEs leading to withdrawal of CABENUVA and study withdrawals, SAEs, or 
other assessments (e.g., follow-up on liver chemistry elevations, pregnancies).  
HIV care providers will be notified of all adverse events and will be requested to 
provide a causality assessment.  
• During the oral lead-in phase (for those initiating CABENUVA for the first time) 
and for the duration of the study, the HIV care providers will remain responsible 
for the medical management of their PLWHIV.   
• HIV care providers will be notified by the IC/ASA of all planned and any 
unplanned missed visits.  The HIV care provider will determine when to start oral 
therapy for planned missed doses, or restart CABENUVA according to the most 
current USPI. 
• If the IC/ASA or the HIV care provider cannot contact the participant following 
missed injections of CABENUVA, this should be documented in the participants 
medical record, and if an injection is not administered within the allotted window 
period, such participants will be removed from the study and the clinical 
management of the participant will remain with the HIV care provider  
Some HIV care providers manage their patients in conjunction with other clinic staff 
members who work with ICs/ASAs and may be better to complete some study 
assessments.  Thus, in Protocol Amendment 4, the completion of study questionnaires 

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and potential interviews to be completed by the HIV Care Providers could potentially be 
completed by other clinical staff members. 
Up to approximately 20 HIV care providers/clinical staff who refer their PLWHIV to a 
study IC/ASA, and after the HIV care provider’s first patient is enrolled into the study, 
the HIV care provider/clinical staff may be asked to complete questionnaires per the SoA 
(Annex 1: Schedule of Activities).   
The duration of study participation for each HIV care provider/clinical staff is 
approximately 8 months after their last PLWHIV has their first visit (LPFV) and received 
CABENUVA IM injections at a participating IC/ASA. 
4.3.3. 
Infusion Center Staff 
Key IC/ASA staff members involved in decision making and/or overseeing daily 
operations at the IC/ASA will participate in the Expert Panel.  IC/ASA staff that are not 
part of the Expert Panel will complete assessments per the SoA (Annex 1) and in the 
POT.  Baseline questionnaires should be completed by IC/ASA staff, prior to the first 
participant enrolled at their center. 
Insurance verification will be done by the ICs/ASAs for all referred PLWHIV that are 
new to CABENUVA.  The IC/ASA staff is responsible for promptly informing the 
PLWHIV and HIV care provider of the outcome of the insurance verification.   
• The IC/ASA and the referring HIV care provider will review and individualize the 
POT for each participant prior to their first injections, if required.  The IC/ASA 
center will explain that medical records may be collected for SAEs or other events 
for their PLWHIV enrolled at their center.  
• At the first study-related injection visit (M1), the IC/ASA staff will obtain the 
participant's informed consent prior to enrolling in the study.  After consent is 
obtained, the IC/ASA staff will administer CABENUVA IM injections as per the 
most current approved prescribing information in the CABENUVA USPI.  
• The IC/ASA will be responsible for scheduling the monthly or every 2-month 
injections, reminding participants when they are scheduled to receive their 
injections, and rescheduling missed injections  
The IC/ASA will immediately notify the participant's HIV care provider for any of 
the following reasons:    
• The participant has missed a dose and/or is outside the dosing window (7 days) 
• The IC/ASA cannot contact the participant to reschedule a missed appointment 
• The IC/ASA learns of an AE or SAE.  The IC/ASA staff will be responsible for 
reporting all AEs/SAEs (refer to Section 10.3), to the HIV care provider.  All 
events should be kept in the participant source documentation.  
• Participant has started a new medication with the potential for drug-drug 
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The HIV care provider will manage all medical and clinical follow-up required, 
including management of adverse events. 
Every injection visit will be recorded as a study visit.  Additional participant contacts will 
not need to be documented as a study visit; however, the results of the viral load or other 
assessments are to be entered into the electronic Case Report Forms (eCRF).   
The IC/ASA staff are responsible for the completion of all eCRF forms.  Refer to Section 
10.3.10, Table 3 for AE/SAE and pregnancy reporting timelines.  
Total duration of study participation for IC/ASA staff is approximately 8 months from 
the time of enrollment of the last participant at that IC/ASA site. 
5. 
IMPLEMENTATION RESEARCH METHODS 
5.1. 
Formative Evaluation Procedures 
HIV care providers will refer their PLWHIV that are interested in receiving 
CABENUVA injections at a participating IC/ASA.  Participants of the study will be 
required to receive all their monthly or every 2-month injections at the IC/ASA, unless 
the injection is given at the HIV care providers office, as part of a routine care visit.   
5.1.1. 
Expert Panel  
The Expert Panel (approximately 10 members) will convene prior to any participant 
enrolment and will develop a CABENUVA implementation blueprint and an IC POT for 
the study.  The pre-determined panel will be comprised of key IC/ASA staff members 
involved in decision making and/or overseeing daily operations at the IC/ASA, selected 
HIV care providers and VHC.  VHC will provide oversight, and participate on the Expert 
Panel, when appropriate to ensure critical components of the process are addressed and 
that the blueprint is complying with the protocol, and the delivery of the study objectives 
and endpoints.  IC/ASA Staff and HIV care provider membership of this panel will be 
chosen after completion of feasibility, and members will be asked to remain on the panel 
for the duration of the Expert Panel.   
Prior to any participant enrollment in the study, the Expert Panel members will 
participate in a brief baseline qualitative interview and a meeting to design the blueprint, 
which will provide guidance to any IC/ASA about the overall process and 
implementation strategies to support CABENUVA initiation and continuation injections 
and will be used for the development and/or refinement of the POT.  Templated analysis 
will occur for rapid coding both instream during the interviews as well as afterwards, if 
necessary, to capture additional information.  Data from all stakeholder interviews will be 
summarized for top level key constructs noted across interviews.   
At the Expert Panel first meeting, the qualitative interview data will be discussed, 
elements for the blueprint that will be used to develop the IC/ASA POT will be 
identified.  This blueprint and POT will direct the entire spectrum of users (participants, 
HIV care providers, IC/ASA staff) on processes including clinical procedures and 
facilitative communication.  This process will follow an evidence-based qualitative 
improvement process (e.g., identifying potential barriers to implementation, generating a 
plan to address it, and ultimately testing through implementation) paired with a nominal 

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group technique.  The nominal group technique involves the ability to ask the Expert 
Panel to rank order different recommendations anonymously then discuss the triaged 
barriers and create an implementation blueprint to test in each cluster or iteration of the 
process.  At the end of the initial meeting, an implementation blueprint draft will be 
prepared and will serve as the foundation for the IC/ASA POT for guiding successful 
implementation.   
Additionally, as part of the blueprint and the POT, the Expert Panel will define which 
labs (i.e, HIV-1 RNA, CD4 cell counts, liver chemistries, or other labs) or other 
procedures are required, and at what timepoints.  The HIV care provider and the IC/ASA 
can add additional labs to the POT, if required, for the clinical management of their 
PLWHIV. 
After agreement on the initial blueprint, the participating IC/ASA sites and HIV care 
providers will begin to deploy the implementation blueprint, including the POT, and 
begin referring appropriate candidates for enrollment for CABENUVA treatment at the 
participating ICs/ASAs.   
The Expert Panel will meet per the SoA (Annex 1: Schedule of Activities) and/or as 
required over the first 6 months, after the first participant was referred, to refine and 
optimize the blueprint and POT if needed.  The revised blueprint and POT will then guide 
the care of the referred PLWHIV.   
At approximately Month 6, the members of the Expert Panel will complete all 
assessments per the SoA (Annex 1: Schedule of Activities), or as required, over the first 6 
months.  The Expert Panel will meet for a final time at Month 6 to analyze key outcomes 
and to optimize the final blueprint.   
As the additional ICs/ASAs are joining the study at the completion of the Expert Panel 
(approximately November 2022 to Q1 2023), the additional sites may revise the 
implementation blueprint outside of the Expert Panel.  There will be a review of the 
blueprint and POT pre-study, at 3-4 months into the study to ensure IC/ASA experience, 
and at the end of study. 
5.1.2. 
Implementation Assessments 
Implementation outcomes align with the specified aims and Proctor and colleague’s 
[Proctor, 2011] implementation outcome recommendations.  Assessments for the Expert 
Panel, HIV care providers/clinical staff, participants and the IC/ASA staff will be 
administered as outlined in Table 1 and in Annex 1.  Baseline assessments for the Expert 
Panel and the IC/ASA Staff should be completed prior to the first participant is enrolled.  
Implementation assessments may also be gathered from IC/ASA staff members who are 
administering CABENUVA outside of this study. 
A baseline analysis and one or more interim analysis will be conducted to provide early 
evaluation of the implementation science primary and key secondary objectives.  The 
timing of the interim/s will be based on when a sufficient number of IC/ASA staff and/or 
study participant questionnaires and interviews have been completed. 
Per Protocol Amendment 4, HIV care providers/clinical staff will be asked to complete 
questionnaires and interviews. 

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Table 1 
Implementation Assessments 
Outcome 
Assessment Level 
Measurement 
Time point 
Feasibility  
Expert Panel*† 
FIM 
Other quantitative 
questionnaires 
Qualitative Interview 
Prior to FPFV, M3, M6 
Prior to FPFV, M3, M6 
 
Prior to FPFV, M6 
HIV Care Providers/ 
Clinical Staff 
FIM 
Other quantitative 
questionnaires 
Qualitative Interview 
M1, M4, M8 
M1, M4, M8 
 
M8 
Participants 
FIM 
Other quantitative 
questionnaires 
Qualitative Interview 
M1, M3, M8 
M1, M3, M8 
 
M8 
IC/ASA Staff 
FIM 
Other quantitative 
questionnaires 
Qualitative Interview 
Prior to M1, M3, M8 
Prior to M1, M3, M8 
 
M8 
Cross study 
Consent Rate 
Show Rate 
Participant Notification 
Provider Notification 
Return rate 
M1- M8 
M1- M8 
M1- M8 
M1- M8 
M1- M8 
Acceptability 
Expert Panel*† 
AIM 
Other quantitative 
questionnaires 
Qualitative Interview 
Prior to FPFV, M3, M6 
Prior to FPFV. M3, M6 
 
Prior to FPFV, M6 
HIV Care Providers/ 
Clinical Staff 
AIM 
Other quantitative 
questionnaires 
Qualitative Interview 
M1, M4, M8 
M1, M4, M8 
 
M8 
Participants 
AIM 
Other quantitative 
questionnaires 
Qualitative Interview 
M1, M3, M8 
M1, M3, M8 
 
M8 
IC Staff 
AIM 
Other quantitative 
questionnaires 
Qualitative Interview 
Prior to M1, M3, M8 
Prior to M1, M3, M8 
 
M8 
Fidelity 
Participants 
Adherence to Target 
date (7 days) 
Monthly 
Process 
evaluation 
HIV Care Providers/ 
Clinical Staff, 
Participants, IC/ASA Staff 
Qualitative Interview 
M8 
CCI

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Outcome 
Assessment Level 
Measurement 
Time point 
Perceptions, 
Facilitators, and 
Barriers/Concerns,  
HIV Care Providers/ 
Clinical Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M4, M8 
Participants 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M3, M8 
IC/ASA Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
Prior to M1, M3, M8 
Preferences 
Participants 
Qualitative Interview 
Other quantitative 
questionnaires  
M8 
M1, M3, M8 
Advantages and 
Disadvantages 
HIV Care Providers/ 
Clinical Staff 
Qualitative Interview  
Other quantitative 
questionnaires 
M8 
M1, M4, M8 
Participants 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M3, M8 
Acceptability of 
receiving and 
referring patients 
HIV Care Providers/ 
Clinical Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M4, M8 
Participants 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M3, M8 
Usefulness of the 
blueprint and POT 
HIV Care Providers/ 
Clinical Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M4, M8 
IC/ASA Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
Prior to M1, M3, M8 
Overall opinion of 
receiving and 
administering the 
injections at an IC 
HIV Care Providers/ 
Clinical Staff 
Qualitative Interview  
Other quantitative 
questionnaires 
M8 
M1, M4, M8 
Participants 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
M1, M3, M8 
IC/ASA Staff 
Qualitative Interview 
Other quantitative 
questionnaires 
M8 
Prior to M1, M3, M8 
Abbreviations: AIM: Acceptability of Intervention Measure; ASA: Alternate Sites for Administration; FIM: 
Feasibility of Intervention Measure; FPFV = First participant first visit, IC = Infusion Center; M: Month 
*Expert Panel includes selected HIV Care Providers and Key IC Staff 
†The Expert Panel will meet as required over the first 6 months to discuss any iterations that are needed to 
refine and optimize the blueprint. 
Only HIV care providers/clinical staff that had patients enrolled into the study will be included in 
assessments post Baseline/Month 1.   

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5.1.3. 
Timepoint Definitions for Completion of Questionnaires and 
Interviews 
Participants:   
• Baseline/Month 1 is defined as the date when a participant signs ICF and 
completes Baseline/Month 1 protocol procedures prior to receiving the first study 
related CABENUVA injections at the IC/ASA. 
• All additional study visits, including those where questionnaires and/or interviews 
are administered at Months 3, and 8, will be anchored off of each participants 
Month 1 visit, so it will reflect the Months on study, regardless of what injection 
schedule they are on and regardless of whether they have missed any injections 
and received oral bridging. 
Expert Panel:  
• Panel members will meet prior to Baseline/Month 1 to design the Blueprint and 
refine the POT 
• Baseline/Month 1 is defined as the date when a participant signs ICF and 
completes protocol procedures and receives the first study related CABENUVA 
injections at any infusion center 
• Month 3 and Month 6 assessments are to be completed after approximately 10 
participants (across all ICs/ASAs) have completed their Month 3 and Month 6 
study visits at any IC/ASA site 
HIV Care Providers/Clinical Staff: 
• Baseline/Month 1 is defined when the HIV care provider’s first patient referred to 
the IC/ASA is enrolled into the study and receives their first injections of 
CABENUVA at the IC/ASA.  HIV care providers/clinical staff  will be asked to 
complete the Baseline/Month 1 questionnaire within 4 weeks of their first referred 
patient enrolled. 
• Month 4 and Month 8 assessments are to be completed when the HIV care 
provider’s first referred patient completes the Month 4 or Month 8 study visits, 
respectively  
― Questionnaires and/or interviews can be completed up to 2 weeks before 
or after the Month 4 or Month 8 study visits 
IC/ASA Staff: 
• Baseline/Month 1 questionnaires should be completed prior to enrollment of the 
first participant at each infusion center  
• Month 1 for each IC/ASA is defined when the first participant enrolls into the 
study at that specific IC/ASA and the participant is administered the first study 
related injections of CABENUVA  

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• Month 2 for potential interviews of approximately 5 IC/ASA staff will be defined 
after at least 1 participant, at their respective IC/ASA site, has completed their 
Month 2 study visits  
• Month 3 and Month 8 will be defined after at least 1 participant, at their 
respective IC/ASA site, has completed their Month 3 or 8 study visits, 
respectively  
― Questionnaires and/or interviews can be completed up to 2 weeks before 
or after the Month 2, Month 3, or Month 8 study visits. 
The full SoA can be found in Annex 1: Schedule of Activities.   
5.1.4. 
Primary Endpoint 
The primary endpoint is participant feasibility at Month 8.  The secondary endpoints 
include the feasibility in HIV care providers/clinical staff and IC/ASA staff, acceptability 
in all groups (HIV care providers/clinical staff, IC/ASA staff, and participants), as well as 
fidelity.  Other feasibility measures as shown in Table 1 will be informed by Pai and 
colleagues [Pai, 2017].  In addition to the quantitative feasibility thresholds, we will 
incorporate data from stakeholder discussions and qualitative data prior to making a final 
rating of success. 
5.1.5. 
Blueprint and Plan of Treatment 
The Expert Panel will construct a blueprint that all ICs/ASAs will follow.  The blueprint 
is similar to standard operating procedures and is intended to provide an overview of 
essential features of implementing CABENUVA as administered via an IC/ASA.  This 
will include procedures and optimal strategies for successful implementation.  This may 
include, but is not limited to:  
• Referral process 
• Time for Insurance processing/Notification of Patient  
• When to order/obtain labs on participants receiving CABENUVA treatment at an 
IC/ASA? 
• Point of service for labs (i.e. at infusion center, at clinic, at an external lab)? 
• How often do HIV care providers want their participants to be seen in their clinic 
while getting CABENUVA at the IC/ASA? 
• How is the HIV care provider notified that the participant received a dose or 
missed a dose? 
• Communication plan for AEs, SAEs, and medical management of AEs/SAEs. 
• What happens when a participant misses a scheduled dose? 
• Scheduling/Rescheduling 
• Appointment Reminders 

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As the Expert Panel will complete their assessments Q4 2022, following this timepoint, 
key IC/ASA staff members involved in decision making and/or overseeing daily 
operations at the IC/ASA, will be given the opportunity to review and revise both the 
blueprint and the POT.  The blueprint and POT will be reviewed and/or revised as 
necessary pre-study, at 3-4 months into the study to ensure experience with participants 
and at the end of study. 
Part of the blueprint will involve a POT, which outlines key information needed to ensure 
the IC/ASA and HIV care providers have communicated necessary information on new 
referrals for CABENUVA.  A typical process for incorporating a new product into 
routine care at ICs/ASAs involves development and/or refinement of a POT, which they 
iterate as needed until the process works seamlessly for communication and engagement 
between HIV care providers, participants, and IC/ASA staff.  The blueprint and POT will 
be iterated to include any IC/ASA letters or other means of advertisements that contacts 
HIV care providers in the community to refer their PLWHIV to them.  This process will 
be documented and incorporated into a final blueprint at the end of the study.  Once the 
initial POT is agreed upon, the IC/ASA will begin incremental real word roll-out into 
their centers that were not previously participating in the study.  Documentation will 
occur around how ICs/ASAs measures success and the impact to further iterate the 
blueprint or not.   
POTs are often unique to the IC/ASA, however, the POT developed in this study will be 
used as a model moving forward for all participating ICs/ASAs.  A POT may include, but 
is not limited to, the following:  
• Patient information (e.g., name, height, weight, year of birth) 
• Diagnosis 
• Pre-medication 
• Dose and frequency of treatment 
• Insurance information 
• Preferred form of communication 
• Additional requests from referring physicians 
5.1.6. 
Scale-up 
The blueprint that was determined to achieve optimal performance through formative 
evaluation will be used to support successful scale-up of CABENUVA IM injections 
across all ICs/ASAs.  Data collected to capture the scale-up will be collected on 
additional participants that enroll to receive CABENUVA, as well as HIV care providers 
that opt into participating in the study, as outlined in Table 1.  The blueprint will be used 
to help other alternate administration facilities set up similar models of care and service 
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5.2. 
Scientific Rationale for Study Design and Research Methods 
The study design is based on the well-established Quality Enhancement Research 
Initiative (QUERI) Four Phase Framework for Implementation Projects [QUERI, 2013].  
These studies are designed to produce valid evidence on operations and impact in a 
rigorous manner while allowing for continued refinement of program design.  The 
formulative evidence of this study maps onto Phase 2 in the QUERI framework in which 
a small clinical trial is conducted to refine and evaluate an implementation program (e.g., 
the process of referring and engaging PLWHIV choosing to receive CABENUVA IM 
injections at an infusion center).  The scale-up of this study maps onto the QUERI 
framework Phase 3, which involves regional roll-out of projects.  This type of design 
allows for real world testing while collecting data on real-time refinements of the 
implementation strategy, measurement of impact on key patient and provider outcomes, 
while having an opportunity to examine what real world scale-up would look like.  The 
measurement follows gold standard implementation outcome guidelines to ensure valid 
measurement of the intended effect.   
Data from advisory boards has demonstrated a preference for having AIFs to expand 
access to CABENUVA when it becomes available in routine care.  To accommodate the 
anticipated increased visits in routine care that are associated with the CABENUVA, an 
expanded capacity for delivery is needed.  Shifting to delivering HIV treatment in AIFs is 
one option to expand uptake of this new treatment.  Research shows that just because an 
effective treatment exists, translation into routine care is slow and often never occurs 
[Bauer, 2019].  As a result, understanding how to efficiently incorporate AIFs into HIV 
care, as well as stakeholder views on this option, could serve as a critical step in uptake 
and sustainment of this novel HIV treatment in the community.   
5.2.1. 
Implementation Frameworks 
To support the QUERI phased design used in this implementation study, per 
implementation methodology it is also guided by 3 gold standard frameworks (covering 
process, determinants and evaluation): Replicating Effective Programs (REP) [Kilbourne, 
2007], the Consolidated Framework for Implementation Research (CFIR) [Damschroder, 
2009] and the Proctor [Proctor, 2011] outcomes framework.   
REP will be used to guide the process of the study.  REP is based on the United States 
Center for Disease Control REP project, which developed systematic and effective 
strategies to prepare HIV treatments for dissemination [Kilbourne, 2007].  REP provides 
a conceptual framework on processes needed to prepare effective interventions for use in 
community settings.  The four steps of REP (see Figure 2; pre-conditions, pre 
implementation, implementation, and maintenance and evolution) ensure key factors are 
thoroughly addressed that are crucial to implementation of effective interventions in 
healthcare settings.  REP is intended to be flexible and adapted to the context in which 
implementation is intended to occur with a new effective intervention. 

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Figure 2 
Replicating Effective Programs 
 
CFIR will serve as the main determinant’s framework guiding examination of factors 
influencing CABENUVA implementation and the qualitative interviews.  This 
framework provides a menu of constructs that can be used to systematically assess 
potential barrier and facilitators to implementation.  Lastly, the Proctor outcomes will 
also be used to guide measurement decisions to ensure the appropriate outcomes are 
measured across the two frameworks [Proctor, 2011].  Notably, acceptability, feasibility, 
and fidelity will be focused on in the proposed study. 
6. 
STATISTICAL CONSIDERATIONS  
The statistical analysis plan will be finalized prior to database release, and it will include 
a more technical and detailed description of the statistical analyses described in this 
section.  This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints.  The learnings over 
the first 6 months will will be used to inform the final data analyses. 
A baseline analysis will be planned to gain insights on the initial assessment of 
implementation science data on primary and key secondary objectives.  It is expected that 
this analysis will be performed with baseline questionnaire data needed from participants 
and IC/ASA staff. 
One or more interim analysis will be conducted to provide early evaluation of the 
implementation science primary and key secondary objectives.  No changes to the study 
conduct will occur. 
The timing of the interim/s will be based on when a sufficient number of IC/ASA staff 
and/or study participant questionnaires and interviews have been completed. 
No formal criteria for stopping or amending the study based on interim analysis results 
will be made.  
A Statistical Analysis Plan will describe the planned baseline/interim analysis in greater 
detail individually.  There is potential analysis for a small number of interviews (N  5) 
with IC/ASA staff at Month 2 to gain an understanding of what is occurring at ICs/ASAs 
during early implementation.   
All interviews will be audio recorded, professionally transcribed by a third-party vendor, 
and reviewed for quality assurance purposes.  Analyses will be done via qualitative rapid 

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coding in Excel and targeted at capturing key concepts of interest for assessing the 
blueprint and POT (including any recommended changes prior to the Month 3 and 
Month 6 assessments). 
6.1. 
Study Size 
This study will include up to 120 participants prescribed CABENUVA by their HIV care 
providers, who will be referred to approximately 35 study infusion centers to receive their 
injections and will be enrolled.  Approximately 20 referring HIV care providers/clinical 
staff will be selected to complete appropriate questionnaires.  Approximately 5 IC/ASA 
staff at each of the IC/ASA locations will be selected to complete the questionnaires.  
Approximately 20 participants will be selected for the Month 8 interview.  In addition, 
approximately 10 referring HIV care providers/clinical staff and 10 IC/ASA staff will be 
selected to conduct interviews.   
The Expert Panel will review the questionnaire data and real-time feedback from the 
Infusion Centers to determine if the blueprint and/or the POT will need to be updated.  
Approximately 10 participants across all ICs/ASAs should have completed the Month 3 
assessments prior to the Expert Panel meetings at Month 3 and Month 6. 
The Acceptability of Intervention Measure (AIM) and the Feasibility of Intervention 
Measure (FIM) are employed to evaluate the acceptability and feasibility of our 
implementation strategy.  The AIM and FIM are validated implementation outcome 
measures [Weiner, 2017a; Weiner, 2017b].  Higher scores for AIM and FIM indicate 
greater acceptability and feasibility.  For these two types of measures, we focus on the 
proportion of participants that agree or completely agree (a score of 4 or higher) across 
all items.  The following power and sample size discussion is based on the primary 
endpoint of feasibility score.  Suppose that the indicators for feasibility success are set at 
80%, then we want to detect a proportion of participants that agree or completely agree (a 
score of 4 or higher) across all items on FIM, which is 80% or higher.  The following 
analysis shows how sensitive the statistical power is to the number of participants 
enrolled. 
Assuming the true proportion of participants that agree or completely agree on FIM 
across all items is 90%>80%, Figure 3 shows the relationship between the study power to 
detect such a proportion and the sample size.  In order to have 80% study power, a 
sample size of 82 participants is needed.  If 106 or more participants are enrolled, we 
would have >85% power to detect such a percentage.  To have 90% power, a minimum 
sample size of 112 participants would be recommended. 
Note: "Enrolled" means a HIV-1 participant agrees to participate in this clinical study, 
following completion of an informed consent process and provided they meet the 
baseline eligibility criteria for participation.  If required, a legally acceptable 
representative may provide the participants agreement to participate in the clinical study 
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Figure 3 
Relationship between Study Power and Sample Size 
 
Further, if we consider a series of possible true percentage, Figure 4 summarizes 
corresponding minimum sample size needed to achieve three target powers (80%, 85%, 
90%).  For instance, if the true percentage is a little higher than 90%, which we 
considered above, say, 93%, then a sample size of 44 participants is required to achieve 
80% power.  And approximately 50 and 63 participants are needed to have 85% and 90% 
power respectively. 
Figure 4 
Relationship between Minimum Sample Size Required and the 
Assumed Percentage 
 

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Considering the real-world uptake of CABENUVA is evolving, we might expect some 
potential low enrollment scenarios at the end of the recruitment period, which could 
impact the study power significantly due to insufficient sample size available.  Under the 
assumption that the true proportion of participants that agree or completely agree on FIM 
across all items is 0.90, 0.93 or 0.95, Figure 5 below demonstrates how the study power 
will vary as the enrollment of participants ranges from 30 to 80.  If the true percentage is 
0.95, the study power is still relatively high and above 70% for all possible sample size in 
this range, while the power might be lower than 70% for sample size within 30-42 but 
keep above 50% for all cases if the true percentage decreased to 0.93.  When the true 
percentage is 0.90, the study power will maintain below the statistically desired 80% as 
the sample size increases from 30 to 80.  In this case, at least 64 participants are needed 
to achieve 60% or above power.  
Figure 5 
Sensitivity of Study Power to Relatively Small Sample Size 
 
Table 2 below provides more details on the associated study power to some selected 
sample size in the range 30-80 with the true percentage equal to 0.90. 

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Table 2 
Relationship between Study Power and Sample Size with Range 30-
80  
True Percentage 
Sample Size 
Power 
0.90 
30 
0.41 
0.90 
36 
0.29 
0.90 
42 
0.38 
0.90 
48 
0.47 
0.90 
54 
0.54 
0.90 
60 
0.61 
0.90 
66 
0.66 
0.90 
72 
0.71 
0.90 
78 
0.75 
0.90 
80 
0.72 
 
6.2. 
Essential Analysis 
The primary endpoint in terms of feasibility is the percentage of participants that agree or 
completely agree (a score of 4 or higher) across all items on the FIM [Weiner, 2017b] at 
Month 8.  For FIM of each study group, the sample percentage and associated 95% 
confidence interval (CI) will be presented.   
One of the secondary endpoints is the change in FIM scores of participants over time at 
Month 3, and Month 8.  In addition to summary of FIM scores at different timepoints, the 
shift table for each item of FIM will be given to display the number of participants who 
completely disagree (scale=1), disagree (scale=2), neither agree or disagree (scale=3), 
agree (scale=4), completely agree (scale=5) at Baseline/Month 1 and the shift of these 
quantities at each timepoint that follows. 
The feasibility composite score will be further refined based on the standard process 
outlined in the blueprint.  The components that are planned to be evaluated at Month 1 
through Month 8 and as part of the composite score are outlined below.  The intention is 
to have a sub-score from the following measures, however, information from the Expert 
Panel will be used to finalize the proposed composite scores prior to data analysis: 
1. FIM Score: Proportion of HIV care providers/clinical staff, participants, and IC/ASA 
Staff respectively that agree or completely agree (a score of 4 or higher) across all 
items on the FIM. 
• Numerator: Number of HIV care providers/clinical staff, participants, and 
IC/ASA Staff respectively that agree or completely agree on FIM (a score of 4 
or greater) across all items 
• Denominator: Total number of HIV care providers/clinical staff, participants, 
and IC/ASA Staff respectively 
2. Consent Rate: Proportion of participants that provide consent to participate in the 
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• Numerator: Number of participants consented 
• Denominator: Number of participants referred to the IC/ASA to receive 
CABENUVA IM injections   
3. Show Rate: Proportion of scheduled injection appointments that are not missed 
a. Numerator: Number of scheduled injection appointments that result in shows 
b. Denominator: Number of confirmed scheduled injection appointments for 
participants 
4. Participant Notification: Proportion of contacts the participant receives from the 
infusion center for missed appointments out of the standard number they should be 
contacted 
a. Numerator: Number of documented times that a participant is contacted by 
infusion center staff regarding a missed appointment 
b. Denominator: Standard number of times that a participant is contacted regarding a 
missed appointment, according to infusion center policy 
5. HIV Care Provider Notification:  
a. 1) Proportion of participants whose information regarding test results are 
communicated to their HIV Care Provider  
― Numerator: Number of participants whose information was communicated to 
the appropriate HIV care provider 
― Denominator: Total number of participants in the study 
b. 2) Proportion of all appointments missed that are communicated to the HIV care 
provider 
― Numerator: Number of missed appointments that are communicated to the 
appropriate HIV care provider 
― Denominator: Total number of missed appointments 
6. Return Rate at Visit N: Proportion of participants that completed any injection at 
Visit N after the completion of (N-1)th injection visit  
a. Numerator: Number of participants who returned to the infusion center and 
completed an injection at Visit N 
b. Denominator: Number of participants who completed an injection at the infusion 
center at the previous visit (N-1) 
― This definition is for any scheduled post-baseline visit.  When N=1, the previous 
visit (N-1) is the baseline visit. 
The estimates of these quantitative measures will be given and corresponding 95% CIs 
will also be presented. 
The feasibility composite score will be informed by the Expert Panel process to ensure it 
matches the critical variables identified by all members of the panel.  Summary details of 
feasibility composite score will be included in the statistical analysis plan. 

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To evaluate the effect of contextual factors on the variability of responses to 
implementation science measurements. subgroup analysis will be undertaken at specified 
assessment timepoints, which include, but not limited to, demographic, baseline 
characteristics, prior clinical experience, initiation method (oral lead in or direct to 
injection or receiving continuation dose), the number of injections received prior to 
enrollment and injection option (monthly or every 2-months) for participants, provider 
type, site type and setting (urban, suburban, rural) for IC/ASA staff, and affiliation for 
HIV care providers. 
6.3. 
Secondary Analysis 
A key secondary outcome is Acceptability:  
AIM Score: Proportion of HIV care providers/clinical staff, participants, and IC/ASA 
Staff respectively that agree or completely agree (a score of 4 or higher) across all items 
on the Acceptability of Intervention Measure (AIM).  The score will be calculated 
approximately at Month 1, Month 4 and Month 8 for HIV care providers/clinical staff, 
and at prior to Month 1/Month 1, Month 3, and Month 8 for participants and IC/ASA 
Staff.   
• Numerators: Numbers of HIV care providers/clinical staff, participants, and 
IC/ASA Staff respectively that agree or completely agree (a score of 4 or higher) 
on AIM across all items 
• Denominators: Total numbers of HIV care providers/clinical staff, participants, 
and I/ASA C Staff respectively 
Other secondary outcomes to be evaluated include:  
• Fidelity: Proportion of injections occurring within target window from target date 
(7 days of target date)  
• Feasibility, acceptability and the process of CABENUVA administration at 
infusion centers from the Expert Panel 
• Perceptions, facilitators, and barriers/concerns by HIV care providers/clinical 
staff, participants, and IC/ASA staff 
• Preference of participants on the location to receive CABENUVA 
• Advantages to receive or refer participants to receive CABENUVA at the infusion 
center from participants and HIV care providers/clinical staff 
• Disadvantages about receiving CABENUVA at the infusion center from 
participants and HIV care providers/clinical staff 
• Acceptability of receiving and referring participants for CABENUVA injections 
at infusion centers from participants and HIV care providers/clinical staff 
• Usefulness of blueprint intervention by IC/ASA staff and the POT for HIV care 
providers/clinical staff 
• Overall opinion of receiving and administering the injection at an infusion center 
by IC/ASA staff, participants and HIV care providers/clinical staff 

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Estimates and associated 95% CI of the quantitative measures above will be presented. 
Qualitative interview data will be summarized by a third party and reported as part of the 
overall study results (clinical study report (CSR)).  Details of these analyses will be 
described in a separate analysis plan provided by the CRO partner under GSK’s 
oversight. 
6.4. 
Other/Tertiary Endpoints 
CCI

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6.5. 
Limitations of the Research Methods 
This is a single-arm study for gathering information on the feasibility and acceptability of 
utilizing an IC/ASA to administer CABENUVA in the US.  As such there are geographic 
limitations.  The study is deliberately non-stratified to reduce limitations on recruitment.   
Thus, this approach may result in some characteristics under- or overrepresented within 
the participants and limited diversity in terms of demographics or introduction of 
confounding factors. 
7. 
PROTECTION OF HUMAN SUBJECTS 
7.1. 
Ethical Approval and Participant Consent 
The protocol, protocol amendments, ICF, and other relevant documents (e.g., 
advertisements) must be submitted to an Institutional Review Board (IRB) and reviewed 
and approved by the IRB before the study is initiated.  
Any amendments to the protocol will require IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants. 
The IC/ASA will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB 
• Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures 
• Providing oversight of the conduct of the study at the ICs/ASAs and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB, and all other applicable local 
regulations 
7.2. 
Participant Confidentiality 
Participants will be assigned a unique identifier.  Any participant records or datasets that 
are transferred to the sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred.  
The participant must be informed that their personal study-related data will be used by 
the sponsor in accordance with local data protection law.  The level of disclosure must 
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also be explained to the participant who will be required to give consent for their data to 
be used as described in the informed consent.  
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
All IC/ASA study staff will ensure protection of participant personal data and will not 
include participant names on any sponsor forms, reports, publications, or in any other 
disclosures, except where required by laws. 
7.3. 
Informed Consent Process 
The IC/ASA will explain the nature of the study to the participant or their legally 
authorized representative and answer all questions regarding the study.  
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB.  
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The IC/ASA authorized person obtaining the informed 
consent must also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF during 
their participation in the study.  
• A copy of the ICF must be provided to the participant or their legally authorized 
representative.  
ViiV Healthcare (alone or working with others) may use participant’s coded study data 
and other information to carry out this study; understand the results of this study; learn 
more about CABENUVA or about the study disease; and publish the results of these 
research efforts.   
7.4. 
Quality Control / Study Monitoring 
In accordance with applicable regulations including GCP, study monitors will contact the 
ICs/ASAs prior to the start of the study to review with the IC/ASA staff the protocol, 
study requirements, and their responsibilities to satisfy regulatory, ethical, and VHC 
requirements. 
When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the eCRF will serve 
as the source document.  The study monitors will monitor the study and IC/ASA site 
activity to verify that the: 
• Data are authentic, accurate, and complete. 

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• Safety and rights of participants are being protected. 
• Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements. 
• The IC/ASA staff and the head of the IC/ASA (where applicable) agrees to allow 
the monitor direct access to all relevant documents. 
8. 
CABENUVA AND CONCOMITANT THERAPY 
The protocol only requires that the participant is initiating or continuing CABENUVA 
IM injections, dosed in accordance with the approved label [CABENUVA USPI, 
EDURANT USPI, VOCABRIA USPI]; no CABENUVA is provided by VHC.  No dose 
reductions, modifications, or changes in the frequency of any components of 
CABENUVA will be allowed during the study beyond what is allowed within the 
approved CABENUVA label 
The IC/ASA will refer to the most recent CABENUVA USPI, for the preparation and 
administration of CABENUVA [CABENUVA USPI]. 
8.1. 
Missed CANENUVA Injections 
Adherence to the CABENUVA monthly or every 2-monthly injection dosing schedule is 
required.  If a participant misses a scheduled injection visit, the referring HIV care 
provider must be notified.  The HIV care provider is responsible for all medical 
management decision for participants after a missed dose, as described in the most recent 
USPI [CABENUVA USPI].  The IC/ASA staff should also notify the Medical Monitor of 
missed injections; however, the Medical Monitor is not responsible for decisions 
regarding medical management of missed injections.   
Any changes in a participant’s ART must be recorded in the eCRF.  This includes oral 
dosing of VOCABRIA and EDURANT or other ART regimens to ensure anti-viral 
coverage during a planned or unplanned missed visit. 
Participants receiving CABENUVA are anticipated to be at risk for development of 
virologic resistance if ART is interrupted.  The time period during which participants are 
at risk for development of virologic resistance may be determined by the period between 
when drug levels fall below therapeutic values and when they fall below levels which 
exert selective pressure on HIV.  This time period will vary by ART agent and is 
dependent upon effective concentration, inhibitory concentration, and half-life.  Plasma 
concentrations of both drugs (cabotegravir, rilpivirine) may be measurable for more than 
one year following IM injections.   
8.2. 
Treatment of an Overdose 
At the IC/ASA, an SOP will be developed for the management of treatment overdose 
following prescribing label information [CABENUVA USPI].  For this study, any dose 
of CABENUVA greater than listed in the prescribing information will be considered an 
overdose.  All overdoses and any treatment for the overdosage should be recorded in the 
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There is no known specific treatment for overdose with cabotegravir or rilpivirine.  If 
overdose occurs, contact the PPD Medical Monitor immediately while monitoring the 
participant and apply standard supportive treatment as required, including monitoring of 
vital signs as well as observation of the clinical status of the patient, and record in the 
participants source documentation.  Consider the prolonged exposure to cabotegravir and 
rilpivirine (components of CABENUVA) following injections when assessing treatment 
needs and recovery.   
In the event of an overdose, the IC/ASA should: 
1. Contact both the HIV care provider and the PPD Medical Monitor 
immediately.   
2. Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF. 
3. Document any signs or symptoms the IC/ASA assess as related to the overdose in 
the eCRF  
Decisions regarding dose interruptions or modifications will be made by the HIV care 
provider and may consult with the Medical Monitor based on the clinical evaluation of 
the participant. 
8.3. 
Concomitant Therapy 
HIV care providers and IC/ASA staff will monitor concomitant medications, referring to 
the most recent USPI [CABENUVA USPI], paying special attention to the 
contraindicated medications and medications with a potential for drug-drug interactions.   
The IC/ASA will note all new concomitant medications and send to the HIV care 
provider.  The IC/ASA should consult with the HIV care provider if any new 
contraindicated or concomitant medications with the potential for drug interactions are 
noted prior to administering CABENUVA.  Contraindicated or concomitant medications 
with the potential for drug interactions must be recorded in the eCRF at each visit.  The 
Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
9. 
DISCONTINUATION OF CABENUVA AND PARTICIPANT 
DISCONTINUATIONS 
9.1. 
Discontinuation of CABENUVA 
It may be necessary for a participant to permanently discontinue CABENUVA.  If 
CABENUVA is permanently discontinued, the participant will not remain in the study.  
See the SoA (Annex 1: Schedule of Activities) and the POT for data to be collected at the 
time of discontinuation of CABENUVA.  All study and CABENUVA discontinuations 
will be captured in the eCRF. 
A participant may have to discontinue CABENUVA due to moderate to severe (as 
clinically determined by the IC/ASA and/or HIV care provider) COVID-19 infection 

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(suspect, probable, or confirmed using the most recent version of the World Health 
Organization (WHO) case definition [WHO, 2020]. 
All study and CABENUVA discontinuations will be recorded. 
9.2. 
Temporary Discontinuation  
The referring HIV care providers will determine if a temporary discontinuation is 
appropriate for their PLWHIV, per the most recent USPI for CABENUVA 
[CABENUVA USPI].  The IC/ASA will capture temporary discontinuations and restart 
information in the eCRF.  If the participant does not restart CABENUVA they will no 
longer be eligible to continue the study.  
If the referring HIV care provider determines a temporary discontinuation of 
CABENUVA is appropriate, he/she is responsible for all medical management 
decisions regarding ART coverage during this time.  The IC/ASA staff should also 
notify the Medical Monitor of temporary discontinuations; however, the Medical Monitor 
is not responsible for decisions regarding medical management of missed injections.   
Any changes in a participant’s ART must be recorded in the eCRF.  This includes oral 
dosing of VOCABRIA and EDURANT or other ART regimens to ensure anti-viral 
coverage during a planned or unplanned missed visit. 
9.3. 
Participant Discontinuation / Withdrawal from the Study 
A participant may discontinue CABENUVA and withdraw from the study at any time at 
their own request or may be withdrawn at any time at the discretion of the IC/ASA or 
HIV care providers for safety (i.e., AE, SAE), behavioural, or compliance reasons (i.e., 
protocol deviation).   
At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA (Annex 1: Schedule of Activities) and the 
POT.  The SoA includes the data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed. 
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.  
9.4. 
Lost to Follow-up 
A participant will be considered lost to follow-up if they fail to return for one or more 
scheduled visits and is unable to be contacted by the IC/ASA or the HIV care provider.  
The following actions must be taken if a participant fails to return to the IC/ASA for a 
required study visit: 
• The IC/ASA must immediately contact the HIV care provider if a participant has 
missed a visit. 

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• The IC/ASA must attempt to contact the participant and reschedule the missed 
visit as soon as possible and counsel the participant on the importance of 
maintaining the assigned visit schedule and ascertain whether or not the 
participant wishes to and/or should continue receiving monthly or every 2-
monthly injections at the IC/ASA.   
• Before a participant is deemed lost to follow up, the IC/ASA and HIV care 
provider must make every effort to regain contact with the participant.  These 
contact attempts should be documented in the participant’s medical record. 
• Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study with a primary reason of “Lost to Follow-up”.  
10. 
MANAGEMENT AND REPORTING OF ADVERSE 
EVENTS AND SAFETY ASSESSMENTS 
Planned time points for all safety assessments are provided in the SoA, Annex 1 and in 
the POT.  Definitions of AEs, SAEs and CV events can be found in Annex 3. 
All AEs, SAEs and clinical laboratory abnormalities should be graded using the Division 
of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events 
[DAIDS, 2017]. 
10.1. 
Clinical safety laboratory assessments 
All Baseline/Month 1 lab assessments should be drawn prior to the 1st study injections.  If 
labs will be taken off-site from the IC/ASA, then the study participant should sign the 
ICF and receive a requisition for a blood draw at another location (i.e., Quest, Labcorp).  
Labs should be drawn 7-10 days prior to the Baseline/Month 1 visit.  Confirmation that 
labs were drawn prior to the 1st study injections are mandatory, relevant labs should be 
added to the eCRF.  If a potential participant has had labs drawn with 10 days of the 
Month 1/Baseline visit, and the HCP is willing to share that data, this data can then be 
used and added to the eCRF. 
Local laboratory assessments for this study will be performed as per the blueprint and the 
POT at local laboratories.  All laboratory reports will be shared with the HIV care 
provider.  See the SRM for additional information. 
• The HIV care provider will determine if any laboratory tests have values 
considered clinically significantly abnormal and will be responsible for the 
participant clinical management.  The IC/ASA and HIV care provider will agree 
if follow-up labs are to be collected at the IC/ASA.  The PPD Medical Monitor 
should be informed of abnormal laboratory tests considered clinically significant.   
• The IC/ASA should document this review and record any HIV care provider 
determination of clinically significant changes occurring during the study as an 
AE/SAE.  The PPD Medical Monitor should be informed.  The laboratory reports 
must be filed with the source documents.  
• If any laboratory test results require a change in participant management or are 
considered clinically significant by the HIV care provider, then the results must 

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be recorded in the eCRF as appropriate (e.g., abnormal lab results that are 
considered an SAE, CABENUVA related or required CABENUVA to be 
discontinued). 
• If laboratory values from non-protocol specified laboratory tests performed at the 
HIV care provider’s local laboratory require a change in participant management 
or are considered clinically significant by the provider then the results must be 
recorded in the eCRF as appropriate (e.g., abnormal lab results that are considered 
an SAE, CABENUVA-related AE, requires CABENUVA to be discontinued, or 
COVID-19 related). 
It is expected that at a minimum, HIV-1 RNA and liver chemistries will be analyzed.  
Other lab assessments will be determined by the Expert Panel (e.g., absolute CD4 cell 
counts) and the POT between the HIV care provider and the IC/ASA. 
• Liver chemistries should include: 
o Aspartate Aminotransferase (AST)/ Serum Glutamic-Oxaloacetic 
Transaminase (SGOT) 
o Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase 
(SGPT) 
o Alkaline Phosphatase 
o Total and direct Bilirubin 
Additional tests may be performed at any time during the study as determined necessary 
by the HIV care provider. 
10.2. 
Liver Chemistry Monitoring 
The HIV care provider and the Medical Monitor must be contacted at onset of liver 
chemistry elevations to discuss participant safety.  Liver event documents (i.e., “Liver 
Event eCRF” and updates, “Liver Imaging eCRF” and/or “Liver Biopsy eCRF”, as 
applicable) should be completed as soon as possible.  See the SRM for more information 
on liver events.  Safety contact information can be found in Annex 4. 
The decision whether to discontinue CABENUVA for abnormal liver tests should be 
made by HIV care provider.  The POT between the IC/ASA and the HIV care provider 
will include the monitoring of liver chemistries and communications between the 
IC/ASA, HIV care provider, and the PPD Medical Monitor.  The PPD Medical Monitor 
may request additional information regarding the results of and/or the monitoring of liver 
chemistries.  Additional information can be found in Section 10.1 and in the SRM. 
10.3. 
Adverse Events (AEs), Pregnancy Exposure and Incident 
Reporting 
Clinical safety data will be collected as outlined in the eCRF.  The complete definitions 
of adverse events (AE) or serious adverse events (SAEs) can be found in Annex 3.  For 
AEs, only those that are considered related to CABENUVA, or that caused the 

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participant to discontinue the study are required to be reported to PPD PVG (See 
Section 10.3.1).  All AEs will be reported to the HIV care provider.   
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative (LAR)) be collected and stored in the 
participants source documentation. 
The IC/ASA staff and any qualified designees are responsible for detecting, 
documenting, and reporting events that meet the definition of an AE or SAE and remain 
responsible for following up AEs that are serious, considered related to CABENUVA or 
that cause the participant to discontinue CABENUVA from the time of the informed 
consent to participants withdrawal or completions of the study.   
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3.10. 
Please call the PPD safety hotline located in  Annex 4 for AE/SAE assistance (i.e., is this 
event an SAE?) and for eCRF entry assistance. 
10.3.1. 
Specific Adverse Events to be Documented in this Study 
Please refer to the most current USPIs for CABENUVA, VOCABRIA and EDURANT 
for additional safety information [CABENUVA USPI; EDURANT USPI, VOCABRIA 
USPI]. 
AEs and SAEs that are required to be recorded as defined in the eCRF include:  
• AEs/Adverse drug reactions* (ADRs) reported at the Baseline/Month 1 visit that 
are considered related to oral VOCABRIA or EDURANT or from the time of the 
last injections 
• AEs/ADRs considered related to CABENUVA  
• All AEs, whether considered related or not, that cause the participant to 
discontinue CABENUVA  
• All SAEs whether related to CABENUVA or not 
• All CV events listed in Annex 3 
• COVID-19 related adverse events 
*An adverse drug reaction (ADR) is defined as a noxious and unintended response to a 
medication related to any doses where there is at least a reasonable possibility, or the 
relationship cannot be ruled out, that it is related to CABENUVA. 
Non serious AEs that are considered not related to CABENUVA or do not lead to 
withdrawal, should be documented in the source documents but will not be documented 
in the eCRF, as this information has been extensively collected in treatment clinical trials, 
no further information is needed to characterize these events. 

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10.3.2. Time Period and Frequency for Collecting AE and SAE Information 
The IC/ASA staff are obliged to collect and report AE information from the time of 
informed consent to the participants withdrawal or completion from the study. 
AEs that begin during the oral lead-in and are considered related to VOCABRIA or 
EDURANT will be recorded as a VOCABRIA or EDURANT-related AE after obtaining 
the informed consent.  
For participants that are already receiving CABENUVA injections prior to enrolling in 
the study, any CABENUVA related AEs reported after their last injections will be 
recorded after obtaining the informed consent. 
• All other events that begin before the administration of CABENUVA IM 
injections but after obtaining informed consent will be recorded as Medical 
History/Current Medical Conditions not as AEs. 
All SAEs will be recorded and reported to PPD PVG immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3.10, Table 3.  The 
IC/ASA will submit any updated SAE data to PPD PVG (Annex 4)within 24 hours of it 
being available. 
The IC/ASA should send all participant reported AEs/SAEs to the HIV care provider and 
request a causality assessment.  The HIV care provider is responsible to the medical 
management of any AE/SAEs. 
The IC/ASA is not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation.  However, if the IC/ASA learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study intervention or study 
participation, the IC/ASA staff must promptly notify PPD PVG. 
10.3.3. 
Methods of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended 
and nonleading verbal questioning of the participant is the preferred method to inquire 
about any adverse event occurrence. 
10.3.4. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the HIV care provider and/or the IC/ASA is required to 
proactively follow each participant at subsequent visits/contacts.  All SAEs will be 
followed until the event is resolved, stabilized, otherwise explained, or the participant is 
lost to follow-up (as defined in Section 9.4).  Further information on follow-up 
procedures is given in the SRM. 
10.3.5. 
Regulatory Reporting Requirements for SAEs 
The definition of SAEs can be found in Annex 3. 

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Prompt notification by the IC/ASA staff to PPD of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the 
safety of VOCABRIA, EDURANT and/or CABENUVA are met.  All SAEs need to 
be reported and recorded to PPD within 24 hours of IC/ASA awareness of the event.  The 
primary mechanism for reporting SAEs to PPD will be the eCRF, which will send an 
automated, electronic safety alert to PPD.  If the electronic system is unavailable, the 
IC/ASA will use the paper SAE form and fax it to PPD. 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of VOCABRIA, EDURANT and/or 
CABENUVA.  The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRBs), ICs/ASAs and the referring HIV care providers. 
The IC/ASA which receives a safety report describing an SAE or other specific safety 
information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the required study documents and will notify the IRB, if appropriate 
according to local requirements. 
Safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded 
to participating HIV care providers as necessary. 
10.3.6. 
Adverse Event Follow-up with the HIV Care Provider 
The IC/ASA should send all AEs and SAEs to the HIV care provider for follow-up 
medical management and to confirm or determine relatedness to CABENUVA.   
10.3.7. 
Causality Assessments 
The causality assessment to CABENUVA is one of the criteria used when determining 
regulatory reporting requirements.   
Please refer to the most recent USPIs for CABENUVA, VOCABRIA and EDURANT for 
additional safety information [CABENUVA USPI; EDURANT USPI; VOCABRIA 
USPI]. 
• For each AE/SAE, the IC/ASA physician must document in the medical notes that 
he/she has reviewed the AE/SAE reported and has provided an initial assessment of 
causality.  All AE/SAEs, along with the initial assessment of causality to 
CABENUVA, should be sent to the referring HIV care provider. 
• There may be situations in which an SAE has occurred, and the IC/ASA physician 
has minimal information to include in the initial report to PPD PVG.  However, it is 
very important that the IC/ASA physician always make an assessment of 
causality for every event before the initial transmission of the SAE data to PPD 
PVG. 
• The HIV care provider is expected to provide a causality assessment.  The HIV care 
provider’s assessment will determine the final causality to CABENUVA.   

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• When a causal relationship is determined by the HIV care provider to be related 
to CABENUVA, this must be recorded as a treatment related AE or SAE as soon 
as possible.  The PPD Medical Monitor should be informed of these events. 
• If the HIV care provider does not provide a causality, it will remain as the IC/ASA 
physician’s initial determination. 
• In the case that the IC/ASA physician determines a non-serious AE that hasn’t 
resulted in discontinuation or withdrawal is not related to CABENUVA, the AE 
would not be entered into the eCRF.  However, if the referring HIV care provider 
determines that the non-serious AE is related to CABENUVA, the IC/ASA staff will 
enter the AE into the eCRF. 
• The IC/ASA staff may change causality as confirmed by the referring HIV care 
provider or when additional follow-up information is available, in which case an SAE 
follow-up report is sent to PPD (via the automated eCRF email) with the updated 
causality assessment included. 
10.3.8. 
Serious Post-Injection Reactions  
Per the current CABENVUA USPI [CABENUVA USPI], participants should be 
observed briefly (approximately 10 minutes) after the injection.  Serious post-injection 
reactions include dyspnea, agitation, abdominal cramping, flushing, sweating, oral 
numbness, and changes in blood pressure).  These events may have been associated with 
inadvertent (partial) intravenous administration.  For more information, please refer to the 
most recent CABENUVA USPI.  These events should be considered as a serious adverse 
event and reported to PPD PVG as described in Section 10.3.10.  
If a participant experiences a serious post-injection reaction, monitor and treat as 
clinically indicated.  In case of a serious post-injection reaction after administration of 
CABENUVA, an ECG may be obtained if medically required.  The ECG should be 
included in the participants source documents. 
The HIV care provider will determine whether the participant should continue to receive 
CABENUVA and remain in the study.  The Medical Monitor should be made aware of 
these events. 
10.3.9. 
Injection Site Reactions 
Injection site reactions (ISRs) are considered drug related as they are related to the 
administration of CABENUVA.  ISRs may include redness, itching, pain or swelling or 
discomfort at the site of the reaction.  All ISRs must be recorded in the eCRF. 
As ISRs have been well characterized throughout the development program of 
CABENUVA and are considered common adverse drug reactions for CABENUVA, 
therefore only serious ISRs and ISRs leading to discontinuation are required to be 
reported to PPD PVG as described in Section 10.3.10. 

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10.3.10. 
Reporting of AEs and Timelines  
If the eCRF is down at the time of notification of these events, complete the applicable 
AE/SAE paper forms or other safety event eCRF and fax the completed forms to PPD 
PVG.  All SAEs should be reported to PPD PVG immediately and under no circumstance 
should this exceed 24 hours.  Please see Annex 4 for safety contact information the SRM 
for additional information on the follow-up of safety events. 
AE or SAE information must include relationship to CABENUVA.  Specific events 
requiring safety follow-up are: 
• SAEs reported at the Baseline/Month 1 visit that are considered related to oral 
VOCABRIA or EDURANT or from the last injection 
• All SAEs (Annex 3) whether related to CABENUVA or not 
The non-serious AEs listed below will require reporting within 3 days to PPD PVG and 
will use the same automated safety alerts within the eCRF.   
• AEs/Adverse drug reactions (ADRs) (Annex 3) reported at the Baseline/Month 1 
visit that are considered related to oral VOCABRIA or EDURANT or from the 
last injection 
• AEs/ADRs considered related to CABENUVA  
o Note: non-serious injection site reactions do not have to be reported to 
PPD 
• All AEs, whether considered related or not, that cause the participant to 
discontinue CABENUVA (including ISRs) 
• Cardiovascular AEs considered related to CABENUVA  
Safety reporting timeline requirements for AE and SAE is summarized in Table 3.  

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Table 3 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
All SAEs 
24 hours 
“SAE eCRF”   
24 hours 
Update “SAE eCRF”  
 
Cardiovascular (CV)a or 
death event 
Initial and follow-
up reports to be 
completed when 
the CV event or 
death is 
reportedb  
‘AE/SAE eCRF’ and 
“CV events” and/or 
“death” eCRF  
Initial and follow-up 
reports to be 
completed when the 
CV event or death is 
reportedb 
‘Updated AE/SAE 
eCRF’ and Update 
“CV events” and/or 
“death” eCRF  
Pregnancy 
24 hours 
“Pregnancy 
Notification Form” 
and SAE (if required) 
Within 24 hours of 
IC/ASA staff 
awareness of 
pregnancy outcome 
“Pregnancy Follow-up 
Form” and SAE (if 
required) 
Non serious ADRsc  
3 days 
eCRF 
3 days 
eCRF 
AEs leading to 
withdrawal 
3 days 
eCRF 
3 days 
eCRF 
a. 
CV events are noted in Annex 3. 
b. 
Additional details and time frames for reporting supplementary information for cardiovascular and death 
events are provided in Section 10.3.12. 
c. 
See Section 10.3.1 for additional information of what AE/ADRs need to be collected. 
10.3.11. 
Pregnancy 
Pregnancy status at enrolment should be confirmed in all participants of child-bearing 
potential (POCBP) by asking their pregnancy status and/or when was the last menses 
period (LMP).  If a participant states they are pregnant, or the LMP was >4 weeks, call 
the HIV care provider to confirm if CABENUVA should be administered.  This 
confirmation from the HIV care provider should be stored in the participants source 
documentation. 
Pregnancy testing will be managed by the HIV care provider.  For POCBP, IC/ASA staff 
should verbally ask about pregnancy status at each visit by asking when was the LMP.  If 
the LMP was >4 weeks, call the HIV care provider before injecting CABENUVA. 
If a pregnancy is reported, the IC/ASA will work with the HIV care provider to 
record pregnancy information on the appropriate form and submit it to PPD within 
24 hours of learning of the pregnancy and should follow the procedure outlined in 
SRM.   
Whilst pregnancies are not part of the study nor documented within eCRF, they will 
however be reported to the sponsor within 24 hours of awareness.  All pregnancies 
will be followed up until outcome (including premature terminations and complications) 
for both mother and child. 
The IC/ASA staff will be provided with necessary “pregnancy notification” and 
“pregnancy follow up” forms and supported by clinical monitor and/or GSK/ViiV 
medical team in complying with regular pregnancy reporting procedures.  Pregnancies 

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will also be reported to the Antiretroviral Pregnancy Registry (APR) by GSK global 
safety.  The IC/ASA staff should not report to APR, to avoid duplication. 
• 
Any participant who becomes pregnant while participating in the study will be 
assessed by their HIV care provider whether to continue or discontinue 
CABENUVA and whether to remain in the study.  Pregnancy information will 
be collected from Day 1 and followed for 52 weeks, including any post-study 
SAEs possibly related to CABENUVA should be reported promptly.   
The pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child(ren).  Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE.  Abnormal 
pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
Any SAE occurring in association with a pregnancy should be brought to the IC/ASA 
attention after the participant has completed the study and considered by the HIV care 
provider as possibly related to CABENUVA, must be promptly reported to ViiV/GSK. 
• 
ViiV/GSK’s central safety department will also forward this information to the 
Antiretroviral Pregnancy Registry.  The international registry is jointly sponsored by 
manufacturers or licensees of antiretroviral (ARV) products.  Additional information 
and a list of participating manufacturers/licensees are available from 
http://apregistry.com/index.htm. 
Prior to the enrolment of pregnant participants or the continuation of CABENUVA 
following pregnancy, the following must occur: 
• HIV care provider confirms CABENUVA can be continued and this 
documentation is stored in the participants source documents. 
• The IC/ASA, along with the HIV care provider, agrees to monitor the outcome of 
the pregnancy and the status of the participant and her offspring. 
10.3.12. 
Cardiovascular and Death Events 
All deaths will be reported and recorded as SAEs.  In addition, all deaths will be required 
to have the eCRF death forms completed by the IC/ASA.  These sections include 
questions regarding the death (including sudden cardiac death and non-cardiovascular 
death).  
The Death eCRF is provided immediately after the occurrence or outcome of death is 
reported.  Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
For any CV events detailed in ANNEX 3, whether or not they are considered SAEs, 
specific CV sections of the eCRF will be required to be completed.  These sections 
include questions regarding the CV event (including sudden cardiac death).  
The CV CRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms.  The CV information should be 

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recorded in the specific cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion.   
10.3.13. 
Medical Device Deficiency  
The vial adaptor, syringe, and needles provided commercially in the study are classed as 
medical devices by the FDA.  If a medical device deficiency or incident is noted during 
the study, please follow the instructions found in the CABENUVA packaging for 
reporting the incident. 
 

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11. 
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rilpivirine after oral induction for HIV-1 infection. N Engl J Med 2020; 382: 1124-35. 
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Pai, N.P., Chiavegatti, T., Vijh, R., et al. 2017. Measures and metrics for feasibility of 
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technologies: the evidence and the framework. Point of care, 16(4), p.141. 
Proctor, E., Silmere, H., Raghavan, R., et al. (2011). Outcomes for implementation 
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Quality Enhancement Research Initiative (QUERI) Implementation Guide. Updated 
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Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir and 
rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020; 382:1112-23. 

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U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
2.1. [March 2017]. Available from: 
https://rsc.tech-res.com/docs/default-source/safety/daids-ae-grading-table-mar2017.pdf 
U.S. Department of Health and Human Services. Food and Drug Administration (FDA). 
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 
Pandemic - Guidance for Industry, Investigators, and Institutional Review Boards. March 
2020. Available at: https://www.fda.gov/media/136238/download. Accessed April 6, 
2020. 
VOCABRIA Prescribing Information (VOCABRIA USPI). 
Weiner, B. J., Lewis, C. C. N., Stanick, C., et al. (2017b). Acceptability of Intervention 
Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of 
Intervention Measure (FIM) (appears in: Psychometric Assessment of Three Newly 
Developed Implementation Outcome Measures). Copyright: Creative Common License. 
Weiner, B. J., Lewis, C. C., Stanick, C. et al. (2017a). Psychometric assessment of three 
newly developed implementation outcome measures. Implementation Science, 12(1), 1-
12. 
WHO Case Definition - March 20, 2020 Version 
(https://www.who.int/publicationsdetail/global-surveillance-for-human-infection-with-
novel-coronavirus-(2019-ncov)). 
 

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ANNEX 1: SCHEDULE OF ACTIVITIES 
Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
1. 
The timing and number of planned study assessments may be altered during the study based on newly available data.  
2. 
The following sequence of events must be followed for participants at the Baseline/Month 1 visit: 1) Informed consent form (ICF) Consent 2) Confirm Inclusion and Exclusion 
criteria 3) complete questionnaires and assessments, 4) Receive first study related intramuscular (IM) injections at the IC/ASA.  Baseline is defined as the Month 1 visit. 
3. E.D = early discontinuation/ withdrawal: This visit should only be conducted if the participant discontinues from the study, and the discontinuation/withdrawal reason should be 
recorded. 
NOTE: Carefully follow the Instructions for Use when preparing and administering CABENUVA IM to avoid accidental intravenous administration 
Clinical and Other Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
Written informed consent must be obtained from 
each potentially eligible participant by IC/ASA 
personnel prior to the initiation of any Baseline 
procedures as outlined in this protocol. 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria will be fully assessed at 
the Baseline/Month 1 Visit. 
Demography 
X 
 
 
 
 
 
 
 
 
 
Pregnancy Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ask POCBP at each visit if they are pregnant and 
ask for the date of their LMP.  See Section 10.3.11 
for additional information. 
For participants on every 2 monthly injections, 
pregnancy status should be confirmed only at 
IC/ASA visits 

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
Height and weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height will only be collected at Baseline. 
BMI will be calculated within the eCRF.  
If possible, the same scale should be used 
consistently throughout the study and participants 
should be asked to remove any excess clothing 
(i.e., coats and shoes).  
For participants on every 2 monthly injections, 
weight would be collected only at IC/ASA visits 
Vital signs: blood 
pressure, heart rate 
X 
Vital signs will be measured according to the POT with the HIV care provider.  All vital 
signs collected must be stored in the participants source documentation at the IC/ASA. 
Vital signs are to be measured after resting in a 
semi-supine position for at least 5 minutes. 
For participants on every 2 monthly injections, vital 
signs would be collected only at IC/ASA visits 
Laboratory 
assessments (HIV1-
RNA, liver 
chemistries, other 
labs per POT) 
X 
 
 
 
 
 
 
X 
X 
The Baseline/Month 1 labs should be collected 
prior to the first study injection (at the 
Baseline/Month 1 visit.  See Section 10.1 for 
additional information 
The HIV care provider is responsible for monitoring 
and any follow-up of elevated HIV-1 RNA and liver 
chemistries in their PLWHIV and to let the IC/ASA 
know if there are any changes to the monthly or 
every 2-month injections.  The HIV care provider 
can request that the IC/ASA draw labs at any time 
or they can perform local labs as required. 
Additional Lab assessments may be obtained per blueprint and the POT with 
the HIV care provider.  All lab reports must be stored in the participants 
source documentation at the IC/ASA. 
Fasting is not required unless otherwise required for a specific lab test. 
Study Treatment:  All injections will be administered according to the CABENUVA USPI. 
CABENUVA IM Injections initiated at IC/ASA, post oral lead-in (1st injections of CABENUVA at the IC/ASA) 
The final oral doses of VOCABRIA + EDURANT, or 
other ART, should be taken on the same day when 
injections with CABENUVA are started. 
Questionnaires and procedures should be 
conducted prior to the injections. 

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
Monthly Dosing (post 
oral lead-in) 
X 
X 
X 
X 
X 
X 
X 
X 
 
IM dosing is expected to occur on the same date of 
the month as determined by Dose 1 - Treatment 
Target Date.  Dosing window is (+ or -) a 7-day 
window 
Every 2-month 
Dosing  
X 
X 
 
X 
 
X 
 
X 
 
Dosing window for every 2-months is +/ - 7-days. 
CABENUVA IM Continuation injections: for those already receiving CABENUVA injections, and who are to get their 
subsequent injections at the IC/ASA 
Note:  To avoid having participants whose last injections are at Month 7 return to the IC/ASA at Month 8, the end of study 
assessments (Month 8) will be completed at Month 7.  Questionnaires and potential interviews will be completed at Month 8 
Questionnaires and interviews should be 
conducted prior to the injections. 
Monthly Dosing 
X 
X 
X 
X 
X 
X 
X 
X 
 
The first study related CABENUVA injections at the 
IC/ASA should be started within 1 month (7-day) 
after the last injections. 
For participants switching from an every-2-month 
continuation injection schedule to a monthly 
continuation dosing schedule, follow the dosing 
instructions in the most recent USPI for 
CABENUVA, pl. 
Every 2-month dosing 
(participants already 
receiving every 2-
month dosing) 
X 
 
X 
 
X 
 
X 
 
 
Dosing window for every 2-month dosing is  7-
days. 
For participants switching from a monthly 
continuation injection schedule to an every-2-
month continuation injection dosing schedule follow 
the dosing instructions in the most recent USPI for 
CABENUVA.,  

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
Concomitant 
medication review 
X 
======================================================  
X 
The IC/ASA will note all new concomitant 
medications and send to the HIV care provider.  
Contraindicated medications and concomitant 
medications with a potential for a DDI per 
CABENUVA USPI will be recorded. 
Adverse Event (AE) 
Review 
X 
======================================================  
X 
See Section 10 for more information on the DAIDS 
grading scale, Section 10.3.7 for guidelines on 
assessment of causality, and Section 10.3.10 for 
AE reporting requirements   
Refer to the Annex 3 for definitions of AEs. 
Serious AEs (SAEs) 
X 
=====================================================  
X 
See Section 10 for more information on the DAIDS 
grading scale, Section 10.3.7 for guidelines on 
assessment of causality, and Section 10.3.10 for 
SAE reporting requirements.  
Refer to the Annex 3 for definitions of SAEs  
Questionnaires and Interviews: Questionnaires and Interviews should be completed before receiving CABENUVA IM injections 
Participants 
Baseline/Month 1 is defined as the date when a participant signs ICF and completes Baseline/Month 1 protocol procedures prior to receiving the first study related CABENUVA 
injections at the IC/ASA 
All additional study visits, including those where questionnaires and/or interviews are administered at Months 3 and 8 will be anchored off of each participants Month 1 visit, so it will 
reflect the Months on study, regardless of what dosing regimen the participant is on (e.g., monthly or every 2 monthly) and regardless of whether they have missed any injections 
and received oral bridging. 

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
Participant 
Questionnaires  
X 
 
X 
 
 
 
 
X 
X 
At Month 1, Questionnaires should be completed 
after signing the ICF and before receiving 
CABENUVA IM injections or within 14 days 
following the Month 1 visit. 
Questionnaires should be completed before 
receiving CABENUVA IM injections or  14 days 
following the last visit. 
Participant Interviews  
 
 
 
 
 
 
 
X 
X 
Interviews will be completed at the participants last 
study Visit: Month 8 or early withdrawal visit.  
Interviews can be completed 2 weeks before or 2 
weeks following the last visit. 
Interviews should be completed before receiving 
CABENUVA IM injections if interviews are 
completed the day the injections are administered. 
Expert Panel: will consist of key IC/ASA staff members involved in decision making and/or oversee daily operations at the IC/ASA, selected HIV care providers that may refer 
PLWHIV, and ViiV Healthcare (VHC).  Panel members will meet prior to Baseline/Month 1 to design the Blueprint (Section 5.1.1) 
Baseline/Month 1 is defined as the date when a participant signs ICF, completes protocol procedures and receives the first study related CABENUVA injections at any infusion 
center. 
Month 3 and Month 6 assessments are to be completed after approximately 10 participants (across all ICs/ASA) have completed their Month 3 and Month 6 study visits at any 
IC/ASA site 
Expert Panel 
Questionnaires 
X (Prior to 
Month 1) 
 
X 
 
 
X 
 
 
 
FIM, AIM (FIM and AIM also completed prior to 
FPFV at the Baseline/Month 1 visit) 
Meetings will be held as required over the first 6 
months to discuss any iterations that are needed to 
refine and optimize the blueprint. 

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
Expert Panel 
Interviews 
X (Prior to 
Month 1) 
 
 
 
 
X 
 
 
 
FIM, AIM (FIM and AIM also completed prior to 
FPFV at the Baseline/Month 1 visit) 
Meetings will be held as required over the first 6 
months to discuss any iterations that are needed to 
refine and optimize the blueprint. 
HIV Care Providers/Clinical Staff 
Baseline/Month 1 is defined when the HIV care provider’s first patient referred to the IC/ASA is enrolled into the study and receives their first study related injections of CABENUVA.  
HIV care providers/clinical staff will be asked to complete the Baseline/Month 1 questionnaire within 4 weeks of their first referred patient enrolled. 
Month 4 and Month 8 assessments are to be completed when the HIV care provider’s first referred patient completes the Month 4 or Month 8 study visits, respectively.  
Questionnaires and/or interviews can be completed up to 2 weeks before or after the Month 4 or Month 8 study visits 
HIV Care Providers/ 
Clinical Staff 
Questionnaires 
X (Within 
4 weeks) 
 
 
X 
 
 
 
X 
 
HIV care providers/clinical staff should complete 
questionnaires within 4 weeks following their first 
patient’s enrolment into the study.  
Only HIV care providers/clinical staff that had 
patients enrolled into the study will be included in 
assessments post Baseline/Month 1.   
HIV Care Providers/ 
Clinical Staff 
Interviews 
 
 
 
 
 
 
 
X 
 
Infusion Center Staff: Baseline questionnaires should be completed prior to the first participant enrolled 
Baseline/Month 1 questionnaires should be completed prior to enrolment of the first participant at each infusion center. 
Month 1 for each IC/ASA is defined when the first participant enrolls into the study at that specific IC/ASA and the participant is administered the first study related injections of 
CABENUVA. 
Month 2 for potential interviews of approximately 5 IC/ASA staff will be defined after at least 1 participant, at their respective IC/ASA site, has completed their Month 2 study visits 
Month 3 and Month 8 will be defined after at least 1 participant, at their respective IC/ASA site, has completed their Month 3, or 8 study visits, respectively.  Questionnaires and/or 
interviews can be completed up to 2 weeks before or after to the Month 3 or Month 8 study visits. 

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Procedure1 
Baseline/ 
Month 12 
Treatment Period (Months) 
E.D.3 
Notes 
2 
3 
4 
5 
6 
7 
8 
IC Staff 
Questionnaires 
X (Prior to 
Month 1) 
 
X  
 
 
 
 
X 
 
Month 1/Baseline questionnaires should be 
completed prior to the first participant enrolled at 
that IC/ASA.  
Questionnaires at other months should be 
completed within  14 days of the scheduled 
month. 
IC Staff Interviews  
 
X 
 
 
 
 
 
X 
 
Month 1/Baseline questionnaires should be 
completed prior to the first participant enrolled at 
that IC/ASA.   
Questionnaires at other months should be 
completed within  14 days of the scheduled 
month. 
 
 

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ANNEX 2. LIST OF STAND-ALONE DOCUMENTS 
Study Blueprint 
Plan of Treatment (PoT) 
Study Reference Manual (SRM) 
 

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Annex 3: AE and SAE Definitions 
Annex 3.1   Definition of an Adverse Event  
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of CABENUVA, whether or not considered related to the 
CABENUVA. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of CABENUVA. 
Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited and that is communicated by a 
participant or their legally authorized representative (LAR) who has signed the 
informed consent.  Unsolicited AEs include serious and nonserious AEs.  Only AEs 
that are considered related to CABENUVA or lead to discontinuation of 
CABENUVA will be recorded.   
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring hospitalization, emergency room visit, or visit to/by a healthcare provider).  
The participants or their LAR(s) will be instructed to contact the HIV care provider 
and/or the IC/ASA staff as soon as possible to report medically attended event(s), as 
well as any events that, although not medically attended, are of concern to the 
participant or LAR.  Detailed information about reported unsolicited medically 
attended AEs will be collected by qualified IC/ASA site personnel, communicated 
to the HIV care provider, documented in the participant’s source documentation, and 
recorded in the participant’s records if related to CABENUVA or leads to 
discontinuation. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by 
participant or their LAR(s) will be collected during the visit with the participants or 
their LAR(s) and by review of available medical records at the next visit.  Any 
unsolicited CABENUVA-related AEs reported during a visit must be documented in 
the participant’s source documentation, communicated to the HIV care provider, and 
recorded in the eCRF by the IC/ASA if the event is considered related to 
CABENUVA or leads to discontinuation.  
Events Meeting the AE Definitions 
• Any abnormal laboratory test results that are collected (hematology, clinical 
chemistry, or urinalysis) or other safety assessments (e.g., electrocardiogram (ECG), 
radiological scans, vital signs measurements) considered clinically significant and 
CABENUVA related in the medical and scientific judgment of the HIV care provider 
and/or IC/ASA physician. 

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AE Definition 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.  If the IC/ASA staff are 
alerted to this, these events should be recorded. 
• New conditions detected or diagnosed after CABENUVA administration at the 
IC/ASA that are considered CABENUVA related or lead to the discontinuation of 
CABENUVA even though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected CABENUVA interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of CABENUVA 
or a contraindicated or concomitant medication with the potential drug-drug 
interactions.  Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae. 
• The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfil the definition of an AE or SAE. “Lack of 
efficacy” or “failure of expected pharmacological action” also constitutes an AE or 
SAE. 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
HIV care provider to be more severe than expected for the participant’s condition. 
• The disease being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
Annex 3.2   Definition of an SAE 
An SAE is defined as any serious AE that meets one of the following criteria: 
• Results in death 
• Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it had been more severe. 

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An SAE is defined as any serious AE that meets one of the following criteria: 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) to the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting.   
• Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfils any other serious criteria, the event is serious.  
When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
• Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
• Is a congenital anomaly/birth defect 
• Other situations: 
• Possible Hy’s Law case: alanine aminotransferase ≥ 3 x upper limit of normal 
(ULN) AND total bilirubin ≥ 2 x ULN (>35% direct bilirubin) or international 
normalized ratio (INR) > 1.5 must be reported as SAE 
• Medical or scientific judgment should be exercised by the HIV care providers 
and/or the IC/ASA physician in deciding whether SAE reporting is appropriate 
in other situations, such as significant medical events that may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These events should usually be 
considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 

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Annex 3.3   Definition of a Cardiovascular Event 
Cardiovascular Events (CV) Definition: 
IC/ASA staff will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
Annex 3.4   Recording and Follow-up of AEs and SAEs 
AE and SAE Recording 
• When a CABENUVA-related AE, AE leading to withdrawal, or any SAE occurs, it 
is the responsibility of the HIV care provider to review all documentation (e.g., 
hospital progress notes, laboratory and diagnostics reports) related to the event. 
• The IC/ASA will then record all relevant AE/SAE (VOCABRIA or EDURANT 
related AEs, CABENUVA-related AEs, AEs leading to withdrawal, all SAEs) 
information. 
• If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under 
study, death due to progression of disease, etc.). 
• It is not acceptable for the IC/ASA or HIV care provider to send photocopies of the 
participant’s medical records to the Medical Monitor or the Sponsor in lieu of 
completion of the eCRF required forms. 
• There may be instances when copies of medical records for certain cases are 
requested.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission. 
• The IC/ASA staff, working with the HIV care provider, will attempt to establish a 
diagnosis of the event based on signs, symptoms, and/or other clinical information.  
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AE and SAE Recording 
documented as the AE/SAE and recorded in the eCRF if it is a VOCABRIA-, 
EDURANT, or CABENUVA-related AE, an AE leading to withdrawal, or an SAE. 
Assessment of Intensity 
All AEs and SAEs reported during the study should be evaluated by the IC/ASA 
physician, working with the HIV care provider, and if an AE/SAE is determined as a 
CABENUVA related AE, leads to discontinuation, or is an SAE, it will be graded in the 
eCRF. 
The IC/ASA staff will capture the SAE causality in the participant’s source notes in a 
timely manner, and the IC/ASA staff or an appropriately delegated team member will 
enter the causality into the eCRF.  CRAs will monitor the participant source 
documentation to confirm that SAE causality is being documented in a timely manner. 
• 
Mild:  An event that is easily tolerated by the participant, causes minimal 
discomfort, and does not interfere with everyday activities. 
• 
Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities. 
• 
Severe:  An event that prevents normal everyday activities – an AE that is assessed 
as severe will not be confused with an SAE.  Severity is a category utilized for rating 
the intensity of an event, and both AEs and SAEs can be assessed as severe. 
Assessment of Causality 
• 
The IC/ASA physician, working with the HIV care provider, is obligated to assess 
the relationship between CABENUVA and each occurrence of each AE and SAE 
reported.  Prior to a participant enrolling in the study, if an AE or SAE should be 
reported and if it is related to oral VOCABRIA or EDURANT, it should be 
documented in the eCRF. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than that a relationship 
cannot be ruled out. 
• The IC/ASA physician, working with the HIV care provider, will use clinical 
judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to CABENUVA 
administration, will be considered and investigated. 
• The HIV care provider and/or IC/ASA physician will also consult the USPIs for 
CABENUVA, VOCABRIA, and EDURANT in their assessment  
• For each AE and SAE, the IC/ASA physician must document in the medical notes 
that they have reviewed the AE/SAE and have provided an assessment of causality 
and have retrieved all required source documentation as available. 

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AE and SAE Recording 
• There may be situations in which an SAE has occurred, and the IC/ASA has minimal 
information to include in the initial report to ViiV Healthcare (VHC).  However, it 
is very important that the IC/ASA physician, working with the HIV care 
provider, always makes an assessment of causality for every event before the 
initial transmission of the SAE data to VHC. 
• The HIV care provider may change their opinion of causality in light of follow-up 
information, and the IC/ASA should send an SAE follow-up report with the updated 
causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AE and SAE 
• The HIV care provider will medically and clinically manage the follow-up of each 
AE and SAE.  If this follow-up information is shared with the IC/ASA, this should 
be recorded.  Information regarding the causality of the AE or SAE can be updated 
based on these investigations by the HIV care provider.  
• If a participant dies during participation in the study, the IC/ASA will provide VHC 
with a copy of any postmortem findings including histopathology, if this is available 
to them.  
• New or updated information will be recorded. 
• 
The IC/ASA will submit any updated SAE data to VHC within 24 hours of receipt 
of the information. 
Annex 3.5   Reporting of SAEs to ViiV/GSK 
SAE Reporting to ViiV/GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting SAEs to PPD and to VHC will be the 
electronic data collection tool. 
• If the electronic system is unavailable, then the IC/ASA will use the paper SAE data 
collection tool to report the event within 24 hours. 
• The IC/ASA will enter the SAE data into the electronic system as soon as it becomes 
available. 
• The IC/ASA physician or a medically qualified sub-physician, working with the HIV 
care provider, must show evidence within the source documents of the review and 
verification of the relationship of each SAE to CABENUVA, VOCABRIA, or 
EDURANT. 
• After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 

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SAE Reporting to ViiV/GSK via Electronic Data Collection Tool 
• If an IC/ASA receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken offline, then the IC/ASA can report this information on a paper SAE 
form (see table below) or to the Medical Monitor by telephone. 
• 
Contacts for SAE reporting can be found in SRM. 
SAE Reporting to ViiV/GSK via Paper Data Collection Tool 
• The IC/ASA staff will complete, scan, and upload the applicable AE/SAE or other 
safety event CRF to SharePoint and will then email Evidera/PPD and 
wilsafety@ppd.com to inform them that an AE/SAE or other safety event has 
occurred and that the applicable form has been uploaded to the specific SharePoint 
folder. AE or SAE information must include the relationship to CABENUVA, and 
the IC/ASA will contact the participant’s HIV care provider urgently to discuss this 
assessment. 
• Evidera/PPD project managers (PMs) and the PPD Pharmacovigilance (PVG) team 
will receive automatic notifications when CRFs are uploaded and will review all 
AE/SAE and other safety event CRFs within one business day.  
• Evidera/PPD PMs will contact the PPD PVG team to ensure that they have received 
the notification.  
• 
The PPD PVG team will inform the GSK/ViiV medical monitor(s), safety team, and 
applicable team members of the event via email and will provide the necessary 
documentation within 24 hours of awareness. The GSK/ViiV medical monitors will 
be given access to the SharePoint site. The safety documents will be viewable 
through SharePoint and will not need to be downloaded.  
 
 

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Annex 4: Contact Information for Reporting of AEs and SAEs 
and Pregnancies 
Study contacts  
Available 24/24 hours and 7/7 days 
PPD Clinical Safety and Pharmacovigilance (PPD PVG) 
SAE Hotline for North America 
Phone   1-800-201-8725 
Fax:      1-888-488-9697 
Email:   WIL Safety (SM) wilsafety@ppd.com 
 
Additional contacts can be found in the SRM. 
 

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Annex 5: Protocol Amendments  
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Annex 5.1  Protocol Amendment 05 (14 November 2022 
The primary and only purpose of this amendment is to update the Sponsor address on the 
Title Page 
Section # and 
Name 
Description of Change 
Brief Rationale 
Title Page 
Updated Sponsor Address 
Location Moved 
Annex 5.1 
Moved the Table of Changes 
from Protocol Amendment 
04 to Annex 5.1  
Moved according to the Protocol 
template 
Annex 5.2  Protocol Amendment 04 (6 October 2022) 
The primary and only purpose of this amendment is to update the Sponsor address on the 
Title Page 
The primary purpose of this amendment is to support the additional Infusion Centers 
The primary purpose of this amendment is to support the additional Infusion Centers 
being added to the study to broaden the geographical area within the US and to scale-up 
the implementation blueprint.  The additional ICs will be initiated between approximately 
November 2022 – 1st Quarter 2023.  Other changes include deletion of Exclusion 
Criteria 4 in Section 4.2.1 to allow participants into the study regardless of how many 
prior (pre-study) injections of CABENUVA they have received at the IC site and to 
remove the recruitment period of 12 months as the recruitment period for some sites may 
be longer than or less than 12 months.   
Section # and 
Name 
Description of Change 
Brief Rationale 
Global Change to 
Sections listed 
below 
Added other clinical staff to 
also be allowed to complete 
questionnaires and 
interviews, represented as 
HIV Care Provider/clinical 
staff 
Some HIV care providers manage 
their patients in conjunction with 
other clinic staff members who, 
work with ICs and may be better 
to complete some study 
assessments 
• Global change to Section 1 Abstract, Section 2.1 Background, Section 2.2 Rationale, 
Section 3. Objectives and Endpoints, Section 4.1. Study Design, Section 4.3.2 HIV 
Care Providers, Section 5.1.2 Implementation Assessments, Section 5.1.3 Timepoint 
Definitions, Section 5.1.4 Primary Endpoint, Section 6. Statistical Considerations, 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 6.1 Study Size, Section 6.2 Essential Analysis, Section 6.3 Secondary 
Analysis, Annex 1 Schedule of Activities 
Global Change to 
Sections listed 
below 
Expert Panel expected 
completion is expected in late 
2022 
Clarification for the additional 
ICs, how the optimized blueprint 
and POT will be revised outside 
the Expert Panel 
• Global change to Section 1 Abstract; Section 2.2 Rationale, Section 4.1 Study 
Design, Section 4.3.2 HIV Care Providers, Section 5.1.1 Expert Panel, Section 5.1.5 
Blueprint and Plan of Treatment 
Through-out 
Minor editorial and 
document formatting 
revisions 
Minor and therefore have not been 
summarized 
Section 1 
Abstract  
 
Moved the Study Design 
section up within the abstract 
Added text regarding the 
additional ICs  
 
 
Removed all text regarding a 
12-month recruitment period 
Revised order for readability in 
light of the changes made  
Increased the approximate number 
of IC sites to include the 
additional ICs 
 
The recruitment period for some 
sites may be longer than or less 
than 12 months 
Section 4.1 Study 
Design 
Modified schema 
In the Participants design removed 
one set of the questionnaire/ 
interview symbols for clarity 
Added footnote to explain how the 
blueprint will be revised outside of 
the Expert Panel 
Section 4.2 Study 
Population 
Removed all text regarding a 
12-month recruitment period 
The recruitment period for some 
sites may be longer than or less 
than 12 months 
Section 4.2.1.2 
Exclusion Criteria 
Removed Exclusion 
Criteria 4 
To allow participants into the 
study regardless of how many 
prior (pre-study) injections of 
CABENUVA they have received 
at the IC 
Section 4.3.2 HIV 
Care Providers  
 
Revision to number of IC 
sites  
 
Increased the approximate number 
of IC sites to include the 
additional ICs  

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 4.3.3 
Infusion Center 
Staff 
Minor text changes 
Clarification of text 
Section 5.1.1 
Expert Panel 
Added text regarding the 
additional ICs entering the 
study 
New information 
Section 5.1.2 
Implementation 
Assessments 
Section 6 
Statistical 
Considerations 
Added baseline analysis 
To gain insights on the initial 
assessment of implementation 
science data on primary and key 
secondary objectives 
Section 6.1 Study 
Size 
Revision to number of IC 
sites 
 
Removed all text regarding a 
12-month recruitment period 
Increased the approximate number 
of IC sites to include the 
additional ICs 
The recruitment period for some 
sites may be longer than or less 
than 12 months 
Annex 1 
Schedule of 
Activities  
Corrected several errors in 
text and in the Month of 
assessment 
 
Clarifications 
Annex 5 Protocol 
Amendments 
Moved Protocol 
Amendment 3 Table of 
Changes to Annex 5 
 
 
Annex 5.3  Protocol Amendment 03 (20July2022) 
Overall Rationale for Amendment 3  
The primary purposes of this amendment are to update Inclusion Criteria 2 in Section 
4.2.1 so that it matches the prescribing information in the CABENUVA USPI and to 
clarify the Schedule of Activities for those participants whose last study injections of 
CABENUVA at the Infusion Center falls on Month 7. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1 
Abstract; Global 
change 
Change “first study 
administration of 
CABENUVA at the Infusion 
Center (IC)” to “first study 
related administration of 
CABENUVA at the IC” 
Revised to align with the new 
Exclusion Criteria 4, excluding 
participants who have received 
more than 3 injections of 
CABENUVA at the IC 
Section 4.1 Study 
Design; Global 
Change 
Remove the location of the 
ICs 
Removed as the study may recruit 
additional sites 
Section 4.1 Study 
Design 
Revision for clarify 
Added timeline for participants 
entering the study already on 
every 2-month dosing  
Section 4.2.1.1 
Inclusion Criteria 
Revised Inclusion Criteria 2 
Revised Inclusion Criteria to align 
with the CABENUBA USPI 
Section 4.2.1.2 
Exclusion Criteria 
Added new exclusion for 
those that have received more 
than 3 non-study 
CABENUVA injections at an 
IC 
Ensure that all participants have a 
similar starting point when 
answering questionnaires at 
Baseline. 
Section 4.3.1 
Participants with 
HIV-1 
Revision of text 
Modified the first paragraph and 
removed the next 2 paragraphs as 
they repeated the text in the new 
paragraph and in Inclusion 
Criteria 2  
Section 4.3.1 
Participants with 
HIV-1; global 
change 
Removed strikethrough text: 
A participant is considered to 
have completed the study if 
he/she has finished all Month 
8 assessments and receive 
their last injections of 
CABENUVA at the IC  
Clarification, as study participants 
can continue to receive 
CABENUVA at the IC after the 
Month 8 assessments 
Section 4.3.2 HIV 
Care Providers 
and Section 6.1 
Study Size 
Revision to number of IC 
sites 
Increased the approximate number 
of ICs as the study may increase 
the number of IC site 
Section 4.3.2 HIV 
Care Providers 
Removed strikethrough text: 
Once insurance verification 
is approved and reviewed 
with the patient, the IC will 
inform the HIV care provider 
Revised to ensure compliance 
with the CABENUVA USPI 

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Section # and 
Name 
Description of Change 
Brief Rationale 
and the patient will initiate 
treatment with the oral lead-
in of VOCABRIA + 
EDURANT per the 
CABENUVA USPI 
Section 4.3.3 
Infusion Center 
Staff 
Removed strikethrough text: 
Completed questionnaires 
will not be collected in the 
eCRF 
Removed as study is moving to 
new system for collecting case 
report forms, and this will include 
IC staff questionnaires. 
Section 5.1 
Formative 
Evaluation 
Procedures 
Text revised 
Repetitious text was deleted 
Section 5.1.1 
Expert Panel 
Text revised 
Changed maintenance injections 
to continuation injections per the 
USPI 
Section 5.1.2 
Implement 
Assessments 
Revised text to align with 
changes in Section 6 
Wording on when an interim 
analysis may be conducted was 
revised for flexibility 
Section 5.1.3 
Timepoint 
Definitions for 
Completion of the 
Questionnaires 
and Interviews 
Deleted the Month 6 
assessment  
IC questionnaire Month 6 
questionnaire assessment was 
removed as this was revised in 
Protocol Amendment 2  
Section 6 
Statistical 
Considerations 
Revised text 
Flexibility was added on the 
number and when an interim 
analysis may be conducted  
Section 6.2 
Essential 
Analysis 
Revised text  
Additional sub-groups were 
included to align with the revised 
Inclusion and Exclusion criteria, 
initiation methods and the number 
of injections received prior to 
enrolment  
Section 8 
CABENUVA and 
Concomitant 
Therapy 
Revised text 
 
 
Deleted sentence 
Text was clarified to ensure that 
all participants were receiving 
CABENUVA per the USPI 
Sentence removed regarding the 
collection points for 
questionnaires 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Annex 1 
Schedule of 
Activities 
Update to include 
information on participants 
whose last study injections 
fall at Month 7 and not at 
Month 8 
 
 
Deleted specific instructions 
for changing injection 
schedule in a participant 
To avoid having participants 
whose last injections are at Month 
7 return to the IC at Month 8, the 
end of study assessments (Month 
8) will be completed at Month 7.  
Questionnaires will be completed 
at Month 8 
Text revised to ensure the HIV 
care provider and IC Staff follow 
the CABENUVA USPI 
Through-out 
Minor editorial and 
document formatting 
revisions 
Minor and therefore have not been 
summarized 
 
Annex 5.4   Protocol Amendment 02 (16 March 2022) 
Overall Rationale for Amendment 02 
The primary purposes of this amendment were to add changes so that the protocol reflects 
the most recent USPI.  The main change was to add in every 2-month dosing.  
Additionally, the objectives and endpoints for the study were reassessed and modified. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Through-out:  
Removed the 2021year of the 
CABENUVA USPI  
 
Added text to reflect the 
addition of every 2-month 
dosing regimen 
Year removed to ensure protocol 
reflects most current USPI. 
 
Every 2-month dosing was 
recently approved by the FDA; 
therefore, the protocol will allow 
enrolment of participants on 
monthly or every 2 month dosing. 
Section 3 
Objectives and 
Endpoints 
 
 
 
Primary, secondary and 
tertiary were modified 
FIM changed from Month 12 
to Month 8  
The real-world strategies for 
CABENUVA uptake have shifted 
mid-study which is causing a shift 
in study approach to recruitment. 
This will be challenging to track 
and likely be a confounding 
variable for these endpoints. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
All 12-month endpoints 
changed to 8 months.  For 
participants, all assessments 
changed to reflect that the 
data will be collected at 1,3 
and 8 months.  For IC staff; 
1, 3, 8 and for HIV Care 
providers, 1, 4 and 8.  No 
changes to expert panel 
assessments. 
Section 4.1 Study 
Design 
Schema and study length 
updated 
Updated version includes 
participants on every 2-Month 
dosing regimen.  Additionally, 
updated the timing of assessments 
and the length of time each 
participant is in the study was 
updated to reflect the reduction in 
timeline from 12 months to 8 
months. 
Section 4.2.1.2 
Study Population 
Sentence changes to read, 
“Participants may be 
excluded from the study, in 
consultation with the HIV 
care provider, based on 
information from the most 
current Prescribing 
Information 
Sentence restructured for clarity. 
Section 4.3.1 
Participants with 
HIV-1  
Added text to include every 
2-month dosing and added a 
paragraph around switching 
to another dosing regimen 
(monthly or every 2-
monthly) 
Updates to include every 2-Month 
dosing. 
Section 5.1. 
Formative 
Evaluation 
Process 
Added changes to reflect 
every 2-month dosing 
regimen and revised some 
sentences for clarification. 
Updates to include every 2-Month 
dosing. 
Section 5.1.1 
Expert Panel   
Sentences restructured for 
clarity. 
Clarification  
Section 5.1.2 
Table 1;   
FIM Changed from Month 12 
to Month 8 throughout the 
document.   
CABENUVA uptake in the real 
world has changed since the initial 
protocol was developed. The 

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Section # and 
Name 
Description of Change 
Brief Rationale 
All 12-month endpoints 
changed to 8 months 
throughout the document.   
For participants throughout 
the document, all 
assessments changed to 
reflect that the data will be 
collected at 1,3 and 8 
months; 
For IC staff; throughout the 
document, Month 1, 3, 8 and 
for HIV Care providers, 1, 4 
and 8.  No change to expert 
panel assessments. 
Table 1 timepoints were 
updated.  M6 changed to M4.  
M12 changed to M8. 
Preferences, advantages, 
disadvantages, acceptability 
of receiving and referring 
patients updated to include 
MM1, MM4, MM8 
duration of the study was changed 
to limit the recruitment period to 
12 months and the treatment 
period to 8 months. Monthly 
assessments have been modified 
to capture timepoints in the study 
that align with these shortened 
time periods. 
 
 
 
 
 
 
The real-world strategies for 
CABENUVA uptake have shifted 
mid-study which is causing a shift 
in study approach to recruitment. 
This will be challenging to track 
and likely be a confounding 
variable for these endpoints 
Section 5.1.4 
Primary Endpoint 
Per the revision in Section 3, 
 
 
 
Alignment with Section 3  
Section 6.1 
Sample Size 
Update to text, figures and 
tables to reflect a potential 
lower sample size 
CABENUVA uptake is not as fast 
as anticipated, which has resulted 
in slower than anticipated 
recruitment 
Section 6.3 
Secondary 
Analysis 
Per the revision in Section 3, 
 
 
 to Section 6.4 
Alignment with Section 3 
Section 8.1 
Missed 
CABENUVA 
Injections 
Added text to reflect every 2-
month dosing regimen 
Updated to include every 2-Month 
dosing 
Section 9.4 Lost 
to Follow-up 
Added text to reflect every 2-
month dosing regimen 
Updated to include every 2-Month 
dosing 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Annex 1 
Schedule of 
Activities 
Added additional text to 
reflect every 2-month 
regimen and added 
Questionnaire completion 
windows for each dosing 
regimen 
Updated to include every 2-Month 
dosing 
Annex 5 
Protocol Amendment 1 
revisions table moved 
Compliance with current protocol 
template 
Through-out 
Minor editorial and 
document formatting 
revisions 
Minor and therefore have not been 
summarized 
 
Annex 5.5  Protocol Amendment 01 (19 November 2021) 
Overall Rationale for Amendment 1  
The primary purposes of this amendment were to add additional secondary endpoints and 
revising safety Section 10 for ease of reading and to enhance the understanding of what 
adverse events (AEs) and serious adverse events (SAEs) are required to be recorded in 
the electronic case report form (eCRF) and what safety events are required to be reported 
to meet regulatory reporting requirements.   
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1 Abstract 
Removed the words “with HIV” 
from participants  
New secondary objectives added 
 
 
New text added to define the other 
quantitative questionnaires 
New text added to include sub-
group analysis including 
participants, human 
immunodeficiency virus (HIV) 
care providers and infusion center 
(IC) Staff 
Consistency of the use of “participant” 
thought-out the protocol 
Change was made in the abstract to 
reflect the changes in Section 3 
Objectives and Endpoints 
Clarification of other questionnaires in 
addition to the Feasibility of Intervention 
Measure (FIM) and Acceptability of 
Intervention Measure (AIM) 
New text and type of analysis added 
Section 2.1 
Background 
Defined HCPs as healthcare 
providers 
Clarification 
Section 2.3 
Benefit/Risk 
Assessment 
Clarification that the United States 
Prescribing Information (USPI) 
contains both the expected benefits 
and the risks of CABENUVA  
New section added 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 3 Objectives 
and Endpoints 
Additional secondary objectives 
and endpoints were added.  For 
clarity with the additional 
secondary objectives, most 
objectives and endpoints were re-
written and combined.  
The tertiary objective “To evaluate 
feasibility of CABENUVA 
administration at infusion centers 
from participants with HIV-1” was 
moved to a secondary objective. 
The tertiary objective “To further 
evaluate trends in feasibility of 
CABENUVA administration at 
infusion centers (via score from 
HIV care providers, participants, 
and IC staff)” was incorporated 
into a secondary endpoint 
 
 
 
 
 
The tertiary endpoint for semi-
structured interviews (SSIs) was 
moved and modified to a secondary 
endpoint.  
 
 
 
 
 
 
Objectives and endpoints added to reflect 
data which will impact feasibility and 
acceptability.  Clarifying text was added 
regarding the other quantitative 
questionnaires and the qualitative 
interview. 
 
 
 
 
 
 
 
 
 
 
 
 
Removed the mention of injection site 
reaction (ISRs) and post-injection 
reactions as those are already being 
captured under CABENUVA related 
events 
Section 4.1 Study 
Design 
Revised Schema to incorporate 
potential interviews with IC staff at 
Month 2 and added 2 footnotes 
The number of participants 
changed from 106 to 120. 
Updated based on change in this 
amendment and clarifications provided 
within the footnotes 
Correction on the sample size   
Section 4.2 Study 
Population 
Text removed: This number will be 
given sequentially in chronological 
order of participant presentation 
according to a numeric roster 
provided by GlaxoSmithKline 
(GSK). 
Text removed as there is no 
randomization in this study 
Section 4.2.1.1 
Inclusion Criteria 
Clarification that “within one 
month” is defined as 28 days 
Clarification to align with the USPI 
Section 4.2.1.2 
Exclusion Criteria 
Added 3 exclusion criteria based 
on information from the 
CABENUVA USPI: 
Contraindications, new health 
condition/prohibited medications 
and Other reasons 
Added to aid the IC staff in making 
exclusionary decisions 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 4.3.2 HIV 
Care Providers  
Change in number of IC sites from 
23 to 24 
Text added to include participants 
who are already receiving 
CABENUVA 
Additional clarification that the 
HIV care provider will manage all 
adverse events (AEs) and will be 
requested to make AE/serious 
adverse event (SAE) causality 
assessments 
Text added through-out this section 
regarding the oral lead-in and for 
missed injections during the study 
An additional IC location was added 
 
Clarification of study populations 
 
 
Clarifications on the expected HIV care 
provider oversight of AE/SAEs 
 
 
 
Clarifications 
Section 4.3.3 
Infusion Center Staff 
Updated text to align with changes 
made in Section 10 
Removed 2 bullets on serious post 
injection reactions and ISRs as 
these are captured under AEs 
related to CABENUVA 
Added a reference to Section 
10.3.10 Reporting of AEs and 
Timelines  
Revised to align with the updated 
information in Section 10 
Removal of redundant text  
Removed specific references to 
Section 10 to reduce potential 
inconsistencies between sections 
Alignment with the revised safety 
Section 10 
Section 5.1.2 
Implementation 
Assessments 
Implementation Assessments table 
updated to reflect changes made in 
Objectives and Endpoints. 
Alignment with Section 3 
Section 5.1.3 
Timepoint 
Definitions for 
Completion of 
Questionnaires and 
Interviews  
Added text to define when the 
potential Month 2 interviews would 
be conducted with IC staff 
Added text to align with the potential 
Month 2 interviews  
Section 5.1.5 
Blueprint and Plan of 
Treatment 
Added text to specify medical 
management of AEs and SAEs  
Clarification 
Section 5.1.6 Scale-
Up 
Added text that the blueprint will 
be used to help other alternate 
administration facilities set up 
similar models of care and service 
delivery.   
Clarification of the use for the study 
blueprint 
Section 6 Statistical 
Considerations 
Text modified to state that the 
statistical analysis plan will be 
finalized prior to database release 
(DBR) and not prior to FPFV 
Text added to clarify the time of 
interim analysis (Month 3 and/or 
Month 6) and the number of 
Clarification on when the statistical 
analysis plan will be finalized 
 
 
Clarification of planned interim analysis 
and a reduction from 50 – 60 participants 
to at least 25 participants  
 

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Name 
Description of Change 
Brief Rationale 
participants (~25) at which these 
will occur. 
Text added to explain the 
possibility of a small number of 
interviews with IC staff at Month 2 
Added text about interview 
procedures and how the interview 
analysis will take place 
 
Additional interviews added to gain an 
understanding of what is occurring at ICs 
during early implementation.   
 
Clarification on interview process 
Section 6.1 Study 
Size 
Updated the number of ICs from 23 
to 24 
Text added to clarify the number of 
HIV care providers, IC staff and 
participants completing interviews 
Update 
 
Clarification 
Section 6.2 Essential 
analysis 
Due to moving some of the 
tertiary/other endpoints regarding 
FIM to secondary, text was updated 
to reflect this in several places. 
New text was added on the 
evaluation of the contextual factors 
on the variability of responses 
Updated text  
 
 
 
New text 
Section 6.3 
Secondary Analysis 
Added the additional secondary 
outcomes 
Added how the qualitative 
interview data will be summarized 
and details of this analysis will be 
included within a separate analysis 
plan 
New text 
Section 6.4 
Other/Tertiary 
Endpoints 
Other/Tertiary endpoints updated to 
reflect changes made in Objectives and 
Endpoints 
 
Clarification 
Section 7.1 Ethical 
Approval and 
Participant Consent  
Subject changed to Participant in 
the header 
Update 
Section 7.4 Quality 
Control / Study 
Monitoring 
The IC Investigator has been 
changed to IC staff. 
Updated for clarity 
Section 8.2 
Treatment of an 
Overdose 
Added the Medical Monitor must 
be contacted, and that signs and 
symptoms related to the overdose 
be recorded in the electronic case 
report form (eCRF) 
Clarification 
Section 10 
Management and 
Reporting of Adverse 
Section 10 was revised, edited and 
sections were added or moved to 
Revisions to the safety section: New and 
revised sections added for additional 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Events and Safety 
Assessments 
improve the information flow 
throughout this section 
Added within the Section Header 
text that this section also has 
information for safety assessments 
and reporting requirements 
Added text that the definitions of 
AEs, SAEs and cardiovascular 
(CV) events were added to 
Annex 3 AE and SAE Definitions 
Added text that the grading of all 
AEs, SAEs and lab abnormalities 
should be graded by Division of 
acquired immune deficiency 
syndrome (DAIDS) 
clarifications and to ensure understanding 
of the information  
Clarification  
 
 
 
New Annex 
 
 
 
 
New grading information included 
 
Original Protocol 
Section 10 
Management and 
Reporting of Adverse 
Events to new 
Section 10.3.4 
Follow-up of AEs 
and SAEs 
Text from original protocol 
Section 10 was moved to new 
Section 10.3.4 to ensure the follow-
up of AEs and SAEs is clear 
Revisions to the safety sections 
Original Protocol 
Section 10.1 Safety 
Assessments and 
Section 10.2.3 
Reporting of AEs and 
timelines and moved 
to new Section 10.3.2 
Time Period and 
Frequency for 
Collecting AE and 
SAE Information 
Heading name and number revised  
Added Pharmaceutical Product 
Development Inc (PPD) 
Pharmacovigilance (PVG) to 
collect all SAEs 
Text added for the HIV care 
provider to provide causality for 
safety events 
Clarified reporting AE/SAEs after 
study conclusions 
Revisions to the safety sections 
Clarified where all SAEs will be reported 
 
Clarification of HIV care provider 
responsibilities 
 
Clarification of safety reporting 
Original Protocol 
Section 10.1.1 moved 
to new Section 10.1 
Clinical safety 
laboratory 
assessments  
Heading number change 
New text added regarding causality 
assessment for lab abnormalities 
Added text to clarify how abnormal 
labs should be recorded in the 
eCRF. 
Revisions to safety section and 
Clarifications  
New text added 
Original Protocol 
Section 10.1.2 moved 
to new Section 10.2 
Liver Chemistry 
Monitoring 
Heading number change 
Added text for the completion of 
liver event eCRF pages  
Added a reference to Annex 4 for 
PPD safety contact information 
Revisions to safety section 
New text added 
 
New Annex added 
 
Original Protocol 
Section 10.2 moved 
to new Section 10.3 
Adverse Events 
Deleted the definition of AEs as 
now included within new Annex 3 
Text from original Protocol Section 
10.2.1 Definition of Adverse 
Revisions to safety section  
 
 

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Section # and 
Name 
Description of Change 
Brief Rationale 
(AEs), Pregnancy 
Exposure and 
Incident Reports 
Events was added and revised in 
new Section 10.3 (collection and 
storage of AEs in source 
documentation and detecting, 
documenting and reporting events) 
Removed text on causality and 
moved and revised this text in new 
Section 10.3.7 Causality 
Assessments 
Added a reference to Annex 4 for 
PPD safety contact information 
 
 
 
 
 
 
 
 
 
New Annex 4 reference 
Original Protocol 
Section 10.2.1 
Definition of 
Adverse Events 
moved to Section 
10.3 Adverse Events 
(AEs), Pregnancy 
Exposure and 
Incident Reports, 
Section 10.3.6 
Adverse Event 
Follow-up with the 
HIV Care Provider 
and Annex 3 AE and 
SAE Definitions 
Text from original Protocol Section 
10.2.1 added and revised into new 
Section 10.3 (collection and 
storage of safety events in source 
documentation and detecting, 
documenting and reporting events) 
Sentence was moved to Section 
10.3.6 to ensure the appropriate 
follow-up by the IC staff to the 
HIV care providers 
Removed the text about defining 
AEs as this was moved and revised 
in Annex 3 
Revisions to safety sections 
 
 
 
 
 
 
 
 
New Annex 3 added 
Original Protocol 
Section 10.2.2 
Adverse Events to be 
Documented in this 
Study moved to new 
Section 10.3.1 
Specific Adverse 
Events to be 
Documented in this 
study 
Heading number change and text 
revised to include the word 
“Specific” 
Added all CV events and COVID-
19 related AEs are to be 
documented 
Added a paragraph regarding non 
serious AEs that are considered not 
related to CABENUVA or do not 
lead to withdrawal, these AEs 
should be documented and stored 
in the source documentation but 
will not be documented in the 
eCRF, as this information has been 
extensively collected in treatment 
clinical trials, no further 
information is needed to 
characterize these events. 
Deleted paragraph regarding 
AE/SAE follow-up as duplicative 
with other safety sections 
Revisions to safety sections 
 
 
New text added 
 
 
Revisions to safety sections 
Original Protocol 
Section 10.2.2.1 
Adverse Drug 
Section deleted and the definition 
of adverse drug reactions (ADRs) 
was added to Section 10.3.1 
Revisions to safety sections 

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CONFIDENTIAL 
 
 
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Protocol Amendment 06 
 
88 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Reaction moved to 
new Section 10.3.1 
Specific Adverse 
Events to be 
Documented in this 
Study 
Original Protocol 
Section 10.2.2.2 
moved to Section 
10.3.8 Serious Post-
Injection Reactions 
Heading number change 
Added text for serious post-
injection reactions reporting 
requirement to PPD PVG 
Revisions to the safety sections  
Clarification of reporting requirements 
Original Protocol 
Section 10.2.2.3 
moved to Section 
10.3.9 Injection site 
reactions 
Heading number change 
Text added for safety reporting 
requirements 
Revisions to the safety sections 
Clarification that all ISRs should be 
recorded in the eCRF, however only 
serious ISRs or those leading to 
withdrawal need to be reported to PPD 
PVG 
Original Protocol 
Section 10.2.2.4 
Serious Adverse 
Events moved to 
Section 10.3.5 
Regulatory Reporting 
Requirements for 
SAEs and Annex 3 
AE and SAE 
definitions 
New Section added and contains 
text from original Protocol 10.2.2.4 
Removed the text about defining 
SAEs as this was moved and 
revised in Annex 3 
Revisions to safety sections  
 
New Annex 3 added 
Original Protocol 
Section 10.2.3 
Reporting of AEs and 
timelines moved to 
Section 10.3.2 Time 
Period and 
Frequency for 
Collecting AE and 
SAE Information and 
Section 10.3.10 
Reporting of AEs and 
Timelines 
Heading number and name change 
One sentence was moved to 
Section 10.3.2 (obligations of the 
IC staff to collect and report AEs) 
New text and a table were added to 
Section 10.3.10 regarding the 
specific safety events and the 
timelines for reporting these events 
to PPD PVG  
Revisions to the safety sections  
 
 
 
New text to clarify reporting 
requirements 
Original Protocol 
Section 10.2.4 
Pregnancy moved to 
Section 10.3.11 
Pregnancy  
Heading number change 
Added text that participants of 
child-bearing potential (POCBP) 
should be asked their pregnancy 
status at each visit and date of last 
menses period (LMP) 
Removed text regarding the 
pregnancy specific addendum 
 
 
Revisions to the Safety sections 
Clarification and added text to the 
schedule of activities (SOA) to further 
support  
 
The protocol is being conducted in 
accordance to the currently approved 
USPI, which does not contraindicate or 
have a warning and precaution against 
the use of CABENUVA during 
pregnancy.  It is a HIV care providers 

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Protocol Amendment 06 
 
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Section # and 
Name 
Description of Change 
Brief Rationale 
 
 
 
 
 
Added text that pregnancies will be 
followed and will include the 
reporting of any post-study SAEs 
Deleted text that the Sponsor needs 
to provide written approval 
decision, after considering whether the 
expected benefit justifies the potential 
risk to the fetus to prescribe or have a 
patient remain on CABENUVA while 
pregnant. 
 
Clarification of reporting requirements 
 
Not required in this study 
 
Original Protocol 
Section 10.2.5 Death 
Events moved to new 
Section 10.3.12 
Cardiovascular and 
Death Events 
Heading name and number change 
Text added that all deaths will be 
recorded and reported as a SAE 
Added new text about 
cardiovascular events and the 
recording and reporting 
requirements 
Added reference to Annex 3 AE 
and SAE Definitions 
Revisions to the Safety sections 
Clarification 
 
New text added 
 
 
 
New Annex added 
Section 10.3.3 
Methods of Detecting 
AEs and SAEs 
New Section on how to reduce bias 
with the collection of AEs and 
SAEs 
Revisions to the safety sections 
Section 10.3.7 
Causality 
Assessments 
New Section added to clarify the 
requirement for the relatedness of 
any safety event to CABENUVA 
Revisions to the safety sections 
Section 10.3.13 
Medical Devise 
Deficiency 
New Section added for the Food 
and Drug Administration (FDA) 
regulatory reporting requirements 
for a medical device incident 
Added the FDA spontaneous incident 
reporting requirement 
Section 11 
References 
New reference added 
Added reference for the DAIDS grading 
scale that was added to Section 10 
Management and Reporting of Adverse 
Events and Safety Assessments 
Annex 1 Schedule of 
Activities 
Added a check for pregnancy status 
at each monthly visit 
Additional labs at the Month 12 
visit have been added 
Added that fasting is not required 
unless otherwise required for a 
specific lab test 
If the early discontinuation (ED) 
visit is not at a scheduled study 
visit, participants would not receive 
CABENUVA injections.  If the ED 
visit is at a scheduled study visit, 
injections would be captured there 
New text added 
 
Updated  
 
 
Clarification 
 
 
 
Clarification by removing the X for 
injections at the ED visit  
 
 

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CONFIDENTIAL 
 
 
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Protocol Amendment 06 
 
90 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
AEs and SAEs comments: added 
links to the relevant Safety sections 
Removed the row for the collection 
of ISRs or post-injection reactions 
as these are included within AEs or 
SAEs. 
Added the potential Month 2 IC 
staff interviews and defined the 
timepoint this could be completed 
 
Revised to ensure consistency in 
information 
Deleted row for clarification on the 
collection of AEs related to 
CABENUVA 
 
Month 2 potential interviews added 
Annex 2.  List of 
Stand-Alone 
documents 
Added Study Blueprint  
Study Specific Pharmacovigilance 
Plan (sPVP) is removed. 
Blueprint is shared with the IC ‘ 
sPVP Document was no longer required 
since this is an interventional study 
Annex 3 AE and 
SAE Definitions 
New Annex added 
Moved the AE and SAE definitions from 
the SRM into the protocol and added in 
the CV definitions 
Annex 4: Contact 
Information for 
Reporting of AEs and 
SAEs and 
Pregnancies 
New Annex Added 
Added PPD PVG and Safety contact 
information  
Through-out 
Minor editorial and document 
formatting revisions 
Minor and therefore have not been 
summarized 
 

Signature Page for  214747 TMF-15719318 v2.0
Signature Page for TMF-15719318 v2.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 29-Mar-2023 08:39:17 GMT+0000
PPD