Lamivudine (3TC) Plus Dolutegravir (DTG) Dual Therapy: a Study on Patients' Experiences and Perceptions
Conditions: HIV Infections
Sponsor: University of Sussex

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Qualitative Protocol Development Tool 
 
 
 
 
 

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FULL/LONG TITLE OF THE STUDY 
 
Lamivudine (3TC) plus dolutegravir (DTG) dual therapy: a study on patients’ experiences and perceptions  
 
SHORT STUDY TITLE / ACRONYM 
 
Patients’ experiences and perceptions of 3TC/DTG dual therapy (the PEDAL Study) 
 
PROTOCOL VERSION NUMBER AND DATE 
 
Version 2.0 03/12/2020 
 
RESEARCH REFERENCE NUMBERS 
 
IRAS Number: 
286277 
 
SPONSORS Number: 
 
 076 VIL/ 286277 
 
FUNDERS Number: 
214249 
 
 

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SIGNATURE PAGE 
 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to the 
principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used for any other 
purpose other than the evaluation or conduct of the investigation without the prior written consent of the 
Sponsor 
I also confirm that I will make the findings of the study publicly available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent account of the 
study will be given; and that any discrepancies from the study as planned in this protocol will be explained. 
 
For and on behalf of the Study Sponsor: 
Signature:  
...................................................................................................... 
 
Date: 
....../....../...... 
Name (please print): 
...................................................................................................... 
 
 
Position: 
...................................................................................................... 
 
 
 
Chief Investigator: 
Signature: 
...................................................................................................... 
 
Date: 04/06/2021 
Name: (please print): 
Giovanni Villa 
 
 
 
 
 

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LIST of CONTENTS 
 
GENERAL INFORMATION 
Page No. 
HRA PROTOCOL COMPLIANCE DECLARATION  
i 
TITLE PAGE 
 
ii 
RESEARCH REFERENCE NUMBERS 
 
ii 
SIGNATURE PAGE 
iii 
LIST OF CONTENTS 
 
iv 
KEY STUDY CONTACTS 
v 
STUDY SUMMARY 
vi 
FUNDING 
 
vii 
ROLE OF SPONSOR AND FUNDER 
vii 
ROLES & RESPONSIBILITIES OF STUDY STEERING GROUPS AND INDIVIDUALS  
 
vii 
PROTOCOL CONTRIBUTORS 
 
viii 
STUDY FLOW CHART 
ix 
PATIENT ACTIVITY PATHWAY 
x 
TIMELINE 
xi 
SECTION  
1. BACKGROUND 
 
1 
2. RATIONALE  
4 
3. THEORETICAL FRAMEWORK 
4 
4. RESEARCH QUESTION/AIM(S)  
8 
5. STUDY DESIGN/METHODS 
8 
6. STUDY SETTING 
15 
7. SAMPLE AND RECRUITMENT 
15 
8. ETHICAL AND REGULATORY COMPLIANCE 
20 
9. DISSEMINATION POLICY 
23 
10. REFERENCES 
23 
11. APPENDICES 
26 
 
 

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KEY STUDY CONTACTS 
 
Chief Investigator 
Dr Giovanni Villa 
Email: G.Villa@bsms.ac.uk 
Phone: +44 7760685755 
Address: Ground Floor, BSMS Medical Research Building, University of 
Sussex, Falmer, Brighton, BN1 9PX 
Study Co-ordinator 
Dr Caroline Ackley 
Email: c.ackley@bsms.ac.uk 
Phone: +44 7511470390 
Address: Ground Floor, BSMS Medical Research Building, University of 
Sussex, Falmer, Brighton, BN1 9PX 
Research Assistant 
Dr Diego Garcia 
Email: d.garcia@bsms.ac.uk 
Phone: +44 7923232006 
Address: Ground Floor, BSMS Medical Research Building, University of 
Sussex, Falmer, Brighton, BN1 9PX 
Sponsor 
University of Sussex 
Email: researchsponsorship@sussex.ac.uk 
Phone: +44(0)1273 872748 
Address: Falmer House, University of Sussex, Falmer, Brighton, BN1 9QF 
Joint-sponsor(s)/co-sponsor(s)  
Not applicable  
Funder(s) 
ViiV Healthcare 
Dr Gill Hilton-Smith 
Email: gill.d.hilton-smith@viivheathcare.com 
Key Protocol Contributors 
Dr Caroline Ackley 
Email: c.ackley@bsms.ac.uk 
 
Dr Giovanni Villa 
Email: g.villa@bsms.ac.uk 
 
Dr Amanda Clarke 
Email: amanda.clarke16@nhs.net 
Consultant in HIV/GUM & Clinical Trials 
Joint Lead HIV/GUM 
Joint CRN Lead for Infection for Kent, Surrey & Sussex 
Honorary Senior Clinical Lecturer, Brighton & Sussex Medical School 
Royal Sussex County Hospital Brighton, UK 
Direct line: 01273 523085 (=ext 3085) 
Secretary: Ms Tania Knights 01273 664731 
Address: 1 Abbey Rd, Kemptown, Brighton BN2 1DH 
 
Mr David Fray 
Service User Forum Chair, Sussex Beacon 
Email: patientrep@icloud.com 
Address: 10 Bevendean Road , Brighton, BN2 4DE 
Committees 
Not applicable 
 
 

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STUDY SUMMARY 
 
Study Title 
Lamivudine (3TC) plus dolutegravir (DTG) dual therapy: a study on 
patients’ experiences and perceptions  
Internal ref. no. (or short title) 
Patients’ experiences and perceptions of DTG/3TC dual therapy (the 
PEDAL Study) 
Study Design 
Qualitative study 
Study Participants 
People living with HIV receiving HIV care at the Lawson Unit and the 
Clinical Research Facility at the University Hospitals Sussex NHS 
Foundation Trust, Brighton, United Kingdom;  
Target population: patients on DTG/3TC 
Control population: patients on other dual and triple therapy 
regimens 
Planned Size of Sample (if applicable) 
• 
Cultural Domain Analysis: at least 80 and up to a maximum 
of 120 participants 
• 
Focus Group Discussions: at least 18 and up to a maximum 
of 60 participants 
• 
In-depth Interviews: at least 18 and up to a maximum of 36 
participants 
TOTAL: 116-216 participants 
Follow up duration (if applicable) 
Not applicable  
Planned Study Period 
April 2021 - September 2022 
Research Question/Aim(s) 
 
Research 
questions: 
What 
are 
patients’ 
experiences 
and 
perceptions of the safety, effectiveness, and tolerability of the 2-
drug regimen DTG/3TC?  What are the unmet needs of patients 
undergoing the 2-drug regimen?  
Aim: To explore patients’ perceptions and experiences of the 2-drug 
treatment regimen DTG/3TC, including potentially unmet treatment 
needs. 
Objectives:  
• 
To investigate patients’ perceptions and experiences on the 
safety, effectiveness, tolerability, and unmet needs of the 
DTG/3TC 2-drug regimen 
• 
To conduct comparative analysis of the safety, effectiveness, 
tolerability, and unmet needs between patients on the DTG/3TC 
2-drug regimen and patients on other two-drug and three-drug 
combinations 
• 
To provide recommendations that improve doctor-patient 
communication, knowledge and understanding of treatment 
plan, and additional care that ought to be considered in patient-
centred, holistic care plans 
 

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FUNDING AND SUPPORT IN KIND 
The research described in the protocol is being funded by ViiV Healthcare.  
 
ROLE OF STUDY SPONSOR AND FUNDER 
The role of the study sponsor is to provide institutional approval to guarantee the study is aligned with research 
ethics.  The study sponsor was not involved in the development of the study. 
The sponsor is the employer of Dr Giovanni Villa, Chief Investigator. The sponsor has had and will have no input 
or influence in study design, conduct, data analysis and interpretation, manuscript writing and dissemination of 
results.  
The Funder is ViiV Healthcare. Quarterly reports will be provided to the funder. The funder will review all material 
for publication or presentation concerning the research activities of the award.  The funder’s role in the study 
design is limited to providing reviewer comments and suggestions.  They have no role or responsibility in 
conducting the study, data analysis and interpretation, manuscript writing, and dissemination of results.  The 
funder does not control the final decision regarding any of these aspects of the study. 
 
ROLES AND RESPONSIBILITIES OF STUDY MANAGEMENT COMMITEES/GROUPS & INDIVIDUALS 
 
The study includes one patient representative whose roles are described according to the INVO Patient and 
Public Involvement briefing.  The patient representative helped adapt in-person methods to online by taking part 
in a User Acceptance Study and providing feedback.  They reviewed and commented on the study protocol.  They 
will help recruit participants from their professional networks.  They will facilitate and support public 
engagement activities at the end of the study.  Their role will be independent from the Sponsor and Investigators 
as they represent patients and the Sussex Beacon. 
 
 

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PROTOCOL CONTRIBUTORS 
- 
Ackley, Villa, Clarke (Authors) 
- 
ViiV Healthcare (Funder) 
- 
University of Sussex (Sponsor) 
- 
Joint Clinical Research Office (JCRO) – University of Sussex 
- 
Patient representatives and co-author: David Fray 
External reviewers:  
• 
Dr Aaron Parkhurst  
UCL, Medical Anthropology 
Areas of expertise: Biosocial Anthropology; Anthropology of the Body; Culture, Ethics and Religion in the 
Clinical Encounter; Anthropology and Psychiatry  
 
• 
Dr Rayner Tan  
National University of Singapore, Public Health 
Areas of expertise: Public Health; Sociology; HIV; Sexually Transmitted Infections; Substance Use 
 
Internal reviewers:  
• 
Professor Melanie Newport  
BSMS, Global Health and Infection 
Areas of expertise: Infectious Diseases; Genetic Susceptibility to Infection and to Tropical Diseases; 
Genetics of African Populations 
 
Patient representatives participated in the User Acceptance Study conducted prior to the submission of this 
protocol to inform how to adapt Cultural Domain Analysis from in-person to online.  Therefore, patient 
representatives have been involved in determining appropriate methods for the study.  They will also participate 
in the dissemination of results through community gatherings in Brighton and at the Brighton and Sussex Medical 
School. 
 
KEY WORDS: 
Qualitative 
Research; 
Perceptions 
and 
Experiences; 
dolutegravir/lamivudine; Tolerability; Safety; Efficacy; Unmet 
Patient Needs 
 
 

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STUDY FLOW CHART 
 
 
Phase IV (July 2022 - Sep 2022)
Analysis of all data sets
Drafting of papers for journal 
submission and conferences
Public Engagement
Phase III (May 2022 - June 2022)
Recruit addition IDI participants if 
needed
Conduct IDIs: 18-36 participants
Preliminary analysis of IDIs
Phase II (Feb 2021 - April 2022)
Recruit additional 
participants as needed
Conduct FGDs: 18-60 
participants
Preliminary analysis of FGDs
Refine In-Depth Interview 
(IDI) tool based on previous 
data analysis
Phase I (June 2021 - Jan 2021)
Recruit study participants:
116-216 participants in total
Conduct Cultural Domain 
Analysis (CDA): 80-120 
participants
Preliminary analysis of CDA 
data
Refine FGD tool based on 
preliminary analysis
Pre-award (Apr - May 2020)
Finalise protocol
Sponsorship by 
University of Sussex
Ethical approval from 
HRA
Finalise materials and 
logistics
Recruit and train 
Research Assistant and 
Research Officer

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PATIENT ACTIVITY PATHWAY 
 
 
 
Eligibility check
•A member of the study team will review the clinic list of the patients attending the HIV clinic one week in advance to identify potential 
candidates
•This activity will be aided by the site personnel. Patients' notes will be reviewed and the site personnel consulted to verify whether the 
candidate should be approached
•Patients will be free to contact the research team after reading the advertising flyers and posters from the waiting area. Their eligibility 
will be subsequently checked and a first study visit planned
Recruitment
•A member of the research team will approach the patient on the day of their clinical appointment. The potential participant will be 
invited to join the study and receive all the patient information material
•If the potential participant gives consent, a written informed consent will be subsequently signed and the date and modality of the first 
study (CDA) visit will be agreed
•Participations to all phases of the study will be offered (FGDs; IDIs)
Cultural Domain 
Analysis
•As detailed below, the participant will choose between in-person or online methods
•In-person visits will be agreed prior arrangement of a suitable environment at the Clinical Research Facility at the University Hospitals 
Sussex NHS Foundation Trust
•At the end of the CDA, participation to the FGDs and IDIs will be confirmed if they had already agreed at the recruitment stage
Recruitment
•In the event of a insufficient number of participants for the FGDs, recruitment will restart as detailed above
Focus Groups 
Discussions
•As detailed below, the participant will choose between in-person or online methods
•In-person visits will be agreed prior arrangement of a suitable environment at the Clinical Research Facility at the University Hospitals 
Sussex NHS Foundation Trust
•At the end of the FGD, participation to the IDIs will be confirmed if they had already agreed at the recruitment stage
Recruitment
•In the event of a insufficient number of participants for the IDIs, recruitment will restart as detailed above
In-depth 
Interviews
•As detailed below, the participant will choose between in-person or online methods
•In-person visits will be agreed prior arrangement of a suitable environment at the Clinical Research Facility at the University Hospitals 
Sussex NHS Foundation Trust

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STUDY TIMELINE 
 
 
Apr-20 May-20
Jun-20
Jul-20 Aug-20 Sep-20
Oct-20 Nov-20 Dec-20
Jan-21 Feb-21 Mar-21
Apr-21 May-21
Jun-21
Jul-21 Aug-21 Sep-21
Oct-21 Nov-21 Dec-21
Jan-22 Feb-22 Mar-22
Apr-22 May-22
Jun-22
Jul-22 Aug-22 Sep-22
Finalise protocol
Sponsor approval
Recruit and train RA & RO
 HA & Ethical approval
Finalise materials & 
logistics
Publish protocol & User 
Acceptance Study
Recruit Participants
Conduct CDA
Preliminary analysis of 
CDA
Refine FGD tool based on 
preliminary CDA
Recruit additional FDG 
participants (if needed)
Conduct FDG
Preliminary analysis of 
FGDs
Refine IDI tool based on 
previous data
Recruit additional IDI 
participants (if needed)
Conduct IDIs
Preliminary analysis of IDIs
Analysis of all data sets
Submitting paper abstracts 
to conferences
Write paper 1
Write paper 2
Public engagement
RA=research assistant; FDG=focus group discussion; IDI=in-depth interviews; BSMS=Brighton and Sussex Medical School
2020
2021
2022

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STUDY PROTOCOL 
Lamivudine (3TC) plus dolutegravir (DTG) dual therapy: a study on patients’ experiences and perceptions 
 
1 
BACKGROUND 
Literature review 
Dolutegravir (DTG), an integrase strand inhibitor (InSTI), is currently recommended for both treatment initiation 
and second/third line therapy for HIV-positive individuals, in combination with either tenofovir disoproxil 
fumarate/emtricitabine (TDF/FTC), tenofovir alafenamide (TAF)/FTC or abacavir/lamivudine (ABC/3TC). 1–3 The 
dual-drug combination DTG/3TC has proven non-inferior to the triple-drug combination TDF/FTC/DTG in the 
GEMINI-1 and GEMINI-2 trials for the treatment of antiretroviral treatment (ART) naïve individuals,4 and the 
European guidelines have introduced this option among recommended first-line regimens.2   Based on the results 
of the ASPIRE,5 LAMIDOL,6 and, ultimately, TANGO studies,7 the dual combination DTG/3TC has also proven to 
be a safe and effective option for treatment simplification of HIV-experienced suppressed individuals on triple 
therapy. 
Dual-drug combinations offer the advantage of a reduced exposure to antiretroviral agents, hence a potential 
reduction in drug-associated side effects in the long-term.8  In addition to DTG/3TC, the SWORD-1 and SWORD-
2 trials have demonstrated the non-inferiority of the dual-drug combination DTG/rilpivirine (RPV) for treatment 
simplification,9 and a novel, long-acting, molecule of the InSTI class, cabotegravir, has proven non-inferior, when 
co-administered with RPV intramuscularly every four weeks, to triple class regimens, in both the FLAIR and ATLAS 
trials.10  Regimens using fewer drugs are undoubtedly destined to represent a larger share of the treatment 
options for people living with HIV in the near future, hence research on their effectiveness and tolerability is 
crucial. 
Although there is clinical evidence of the safety, effectiveness, and tolerability of dual-therapy regimens,8 there 
is limited insight into patient experiences and perceptions of dual-drug combinations, including the DTG/3TC 
regimen.  In our study, we intend to conduct a comparative qualitative analysis to explore patients’ experiences 
and perceptions of dual-therapy regimens, including potentially unmet treatment needs and reported outcomes 
for those already on this drug combination.  This study would be the first of its kind to provide patient-centred 
insight into this specific treatment combination and to provide recommendations for improved clinical care. 
Study description 
We propose a three-phase comparative study with a control population (i.e., HIV-positive individuals on other 
dual therapy regimens and triple ART) and the target population (i.e., HIV-positive individuals on dual DTG/3TC 
regimen) (Figure 1).  The control population will include a group on dual regimens other than DTG/3TC and a 
group on triple therapy.  In the control group of patients receiving dual therapies, we will include patients (i) on 
Juluca (DTG/rilpivirine[RPV]), (ii) on boosted darunavir plus lamivudine (DRV/r or DRV/c + 3TC), and (iii) on 
boosted darunavir plus raltegravir (DRV/r or DRV/c + RAL).  The target population will include patients on 
DTG/3TC.  The addition of the control group of patients on other dual therapies will allow us to tease out the 
particular characteristics of the dual DTG/3TC beyond the mere reduction of molecules employed for the 
treatment. 
 
 
 

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Figure 1. Target and control populations. The arrows indicate that the comparative analysis will take place 
between the target population and the two control groups separately. 
 
We suggest that a comparative study including the target and control populations will allow us to better 
understand patient perceptions and needs as related to the variables of (i) safety, (ii) effectiveness, (iii) 
tolerability, and (iv) unmet needs.  This is because DTG/3TC will not be experienced and perceived in isolation 
from patient’s previous drug regimens or from other patients on different drug regimens.  When a participant 
on DTG/3TC describes their experiences and perceptions, they will be making a comparison to a ‘time before’ or 
to ‘an other’.  For example, we anticipate patients to describe current experiences of DTG/3TC effectiveness in 
comparison to a time they were on another drug regimen or in comparison to a friend/known person on another 
drug regimen (e.g. ‘DTG/3TC is more effective than my previous treatment’ or ‘DTG/3TC seems to be less 
tolerable because my friend is on a different regimen and has fewer side-effects’). This supports the need to 
explore other drug regimens through a control group so that comparisons that arise in the data will have a 
reference point rooted in data.  In short, if a patient says ‘DTG/3TC is safer than my previous treatment’ we can 
understand not only experiences on DTG/3TC, but also how it compares to other treatments. 
Additionally, the subjective nature of these variables means that each person will have a different understanding, 
meaning, perception, and experience of the study variables.  ViiV Healthcare, the researchers, and health care 
providers will have one, or more, way of defining the variables, but there is added value in exploring what they 
mean to patients.  By widening our participant population to not just include the target population, but to also 
include the control groups we will gain a more in-depth understanding of what these variables mean to patients.  
DTG/3TC 
Target Population 
2 NRTIs + 1 NNRTI 
2NRTIs + 1 INSTI 
2 NRTIs + 1 PI/b 
 
Control population on triple therapy 
DTG/RPV 
DRV/b + 3TC 
DRV/b + RAL 
 
Control population on dual 
regimens 

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This will ensure conceptual and operational alignment of the variables between patients and researchers.  So, 
when we report findings from the study on safety or tolerability, there is conceptual and linguistic alignment. 
The ‘phases’ refer to the order in which specific methods will be deployed and findings preliminarily analysed.  
In Phase I we will deploy Cultural Domain Analysis (CDA), a type of structured interview aimed at understanding 
how people in a group think about lists of things that somehow go together. CDA will help us to better understand 
patient unmet needs.  After data collection we will conduct preliminary analysis to refine and improve our Focus 
Group Discussion (FGD) questions and approach.  In Phase II we will conduct FGDs to gain deeper knowledge of 
patient unmet needs and to begin exploring the variables safety, efficacy, and tolerability.  We will conduct 
preliminary analysis of the FGDs to refine the questions and approach we take in In-Depth Interviews (IDI).  In 
Phase III we will conduct IDIs to gain expert knowledge and understanding of the variables safety, efficacy, and 
tolerability.  We will conduct preliminary analysis of the data.  Finally, we will analyse all data sets, prepare journal 
articles, conference papers, and share findings through public engagement with both the Brighton and Sussex 
Medical School and the Sussex Beacon. 
We will ask the control population to draw on their knowledge of the DTG/3TC regimen, and the target 
population to share their experiences on DTG/3TC; both in relation to the above-mentioned variables.  By asking 
the control population about the DTG/3TC regimen (as opposed to their current care plan) we will illuminate 
potential gaps in knowledge and understanding about the DTG/3TC regimen, as well as potential misconceptions 
among HIV patients in treatment about the 2-drug therapy. 
We will also ask the control population about their current dual and triple therapy regimens and the target 
population about their previous experiences on triple therapy or alternative dual therapy combinations before 
switching to the DTG/3TC regimen; both in relation to the above-mentioned variables.  By including exploration 
of different treatments, we will gain understanding of whether patients perceive the new regimen to be safer, 
effective, and more tolerable, as well as if they feel previously unmet needs are now met on the new treatment 
plan.  We can also gauge the potential interest and/or concern/worry/fear that patients on triple and alternative 
dual therapies may feel about the future direction of HIV treatment.   
This data will enable us to provide recommendations for improved doctor-patient communication and health 
education about the 2-drug and DTG/3TC regimen. It may also allow us to identify psycho-social concerns that 
support teams should be aware of or anticipate as patient treatment plans change. 
Study population 
The Lawson Unit and the Clinical Research Facility at the University Hospitals Sussex NHS Foundation Trust 
provide HIV care for a population of around 2,500 individuals living with HIV.  The HIV cohort is composed 
predominantly by men (~85%).  In 2018, prevalence of HIV infection in the general population in Brighton and 
Hove exceeded 5 per 1,000 in the population aged 15 to 59 years in some areas, representing one of the highest 
figure of the United Kingdom; 50% of PLWHIV in Brighton and Hove are over 50 years old, so the prevalence may 
not include under 59’s.11,12  Brighton and Hove was the first city in the UK to achieve “Fast Track City” status in 
2016; the most recent data from Brighton show that 93% of people living with HIV know their status, 99% of 
those are on treatment and 98% of those on treatment have an undetectable viral load.13  
People living with HIV still experience stigma and we acknowledge that members of the study population may 
experience it themselves.  Stigma may be experienced in the forms of self-stigma, perceived and/or anticipated 
stigmas. Self-stigma is ‘a stigmatized group member’s own adoption of negative societal beliefs and feelings, as 
well as the social devaluation, associated with their stigmatized status’.14 Perceived stigma is the ‘perceptions 
about how stigmatized groups are treated in a given context’ and anticipated stigma is the ‘expectations of bias 

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being perpetrated by others if their health condition becomes known’.14 The drivers of stigma might be rooted 
in fear, judgement, blame, stereotypes and prejudice while the facilitators might be social and gender norms, 
health policy, and the legal environment. Additionally, experiences of stigma can vary from demographic and 
length of time since diagnosis. We acknowledge that participants in this study as well as those who do not 
participate may experience HIV-related stigma, therefore we have included a patient representative, Mr. David 
Fray, and several independent organisations to support participants who may want to talk about any questions 
or issues that arise before the study, while taking part in the study, and upon completion of the study.  We will 
also hold a public engagement event in partnerships with the Sussex Beacon in Brighton so that the findings of 
the study can be disseminated and discussed amongst the HIV community with the hope of improving patient 
care and experiences. 
 
2 
RATIONALE  
In this qualitative study we propose to investigate if patients perceive and experience the DTG/3TC 2-drug 
regimen as beneficial according to the variables of safety, effectiveness, tolerability, and unmet needs, including 
comparison with other 2 and 3-drug regimens.  In other words, rather than measuring viral load to determine 
‘benefit’ we are asking patients to tell us of their experiences and perceptions of DTG/3TC to determine ‘benefit’.  
It is possible some patients might not perceive their experiences as positive and thus feel they have not 
benefitted from the drug regime, regardless of their viral load or side effects.   
We argue that this is valuable information for ViiV Healthcare and the future of HIV treatment more generally 
because patients not only need their viral loads to be managed and ideally supressed, but they also need to feel 
that they are benefiting from whatever drug regime they are on.  The risk is that if patients do not feel they are 
benefitting, then they might not adhere to treatment regimens or they might request healthcare providers to 
administer different treatment regimes, ones they perceive more positively.   
We suggest the primary objective is to investigate patients’ perceptions and experiences on the safety, 
effectiveness, tolerability, and unmet needs of the DTG/3TC 2-drug regimen.  The secondary objective is to 
conduct comparative analysis of the safety, effectiveness, tolerability, and unmet needs between patients on the 
DTG/3TC 2-drug regimen and patients on other two-drug and three-drug combinations.  The study aims to 
analyse and disseminate the data collected, and to provide recommendations that improve doctor-patient 
communication, knowledge and understanding of treatment plan, and additional care that ought to be 
considered in patient-centred, holistic care plans.   
 
3 
THEORETICAL FRAMEWORK 
The theoretical framework that informs this study is rooted in the branch of medical anthropology called Critical 
Medical Anthropology (CMA).  We apply this theoretical approach to the micro-social and individual levels of 
analysis in the health care system 15 by studying patients’ experiences and perceptions of the DTG/3TC regimen 
(see Figure 1).  Through this approach we can better understand the human psychobiological system 
(psychological and biological connection), patient’s experiential responses to illness and their personal support 
networks, and physician patient interactions all in relation to the DTG/3TC treatment regimen and future 
direction of 2-drug HIV treatment.  Patients understand, perceive, and experience the DTG/3TC regimen within 
the social, political, and economic systems that structure our world.  Although this study does not focus on the 
political and economic world order, we feel it is important to contextualise the study of health and illness in such 
a theoretical framework.  In what follows we justify CMA as a guiding theoretical framework and describe how 
CMA has been integral to the study of HIV/AIDS.  We describe ‘the social’ part of this study by focusing on the 

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‘social’ lives of medicines where medicines are objects that have the power to influence social and 
biopsychological relations at the individual and micro-social levels. We take the DTG/3TC drug regimen to be 
more than a series of tablets consumed to control viral load.  We take the tablets to also be social objects that 
we follow through the treatment process in an effort to understand the individual and inter-personal interactions 
that comprise the ways that patients perceive and experience tolerability, effectiveness, and safety of the 
DTG/3TC regimen. 
Critical Medical Anthropology 
Critical medical anthropology (CMA) is a branch of medical anthropology that was coined in 1982 by Baer and 
Singer in a paper presented at the American Anthropological Association meeting16. CMA is a theoretical 
perspective that understands health issues within the political and economic contexts that ‘pattern human 
relationships, shape social behaviours, condition collective experiences, reorder local ecologies, and situate 
cultural meanings’ (ibid. pg. 43).  Central to the CMA approach to the study of health and disease is (1) close 
Figure 1: Levels of health care systems  

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attention to ‘ecological, biological and cultural factors;’ (2) consideration of the ‘political and economic forces 
that influence disease patterns and affect access to health care resources;’ and (3) the ‘opportunity for health-
promoting interventions’ (pgs. 10-11).17  CMA can provide crucial information on environments of risk that 
contribute to individual diseases as well as syndemics (sets of interactive problems) and it can provide insight 
into networks of communication and trust that connect people.18 
CMA differs from the popular public health theory social determinants of health (SDH).  In 2004, the WHO 
Commission on Macroeconomics and Health created the Commission on Social Determinants of Health, however 
the SDH approach tends to ignore the political economy of health, which is central to CMA.  Factors often 
identified as SDH include poverty, (un)employment, stress, inequalities in housing, education, social inclusion, 
nutrition, and lifestyle factors like ethnicity and sexual behaviour.16 In contrast, CMA not only identifies such 
factors, but also attempts to understand the broader context and causes of inequality, poverty, unemployment, 
etc.  CMA reaches beyond identifying factors like sexual behaviour as a determinant of health to understanding 
what shapes those behaviours in the first place.  The social determinants of health approach fails to consider the 
capitalist world system in which the political, economic, and social processes that shape the quality of 
determinants are located.19  We take the social systems in which patients and medicines move to be embedded 
with and in interaction with the political and economic structures that order our world.  Medicines are social 
objects that this study follows to reveal individual perceptions and experiences of treatment, as well as support 
networks and patient-provider relationships all located within a complex world order. 
CMA draws on the theoretical assumptions of critical theory, a social theory oriented toward critiquing and 
changing society as a whole while ‘decreasing domination and increasing freedom in all their forms’.20  It is built 
on the scientific method (namely empiricism and objectivity), while recognising that reality is conditioned by 
social circumstance and open to critical examination and debate.  Science emerged and operates within a given 
set of cultural circumstances that are influenced by the worldview and values particular to those circumstances.16  
The scientific method demands open and constant critique and self-examination (ibid.), which drives the way we 
apply CMA in the study design (as an iterative process). 
 
Critical Medical Anthropology and HIV/AIDS 
The anthropological study of HIV/AIDS drastically shifted in the mid-1990s when Merrill Singer applied the 
theoretical framework of CMA16,21 to the study of HIV/AIDS.  In his article ‘AIDS and the Health Crisis of the U.S. 
Urban Poor; The Perspective of Critical Medical Anthropology,’ Singer suggests that the social identity of 
HIV/AIDS in the US has been shaped by social relations across class, race, gender, and sexual orientation, as well 
as by public health categories of disease.  To study the social identity of AIDS is to study the human biocultural 
experience, and how the disease affects the ways we live and organize society.22–24 The disciplines we deploy to 
study this new reality are also affected and anthropologists and social scientists should ‘be professionally 
suspicious of our categories and models; we should be aware of their historical and cultural contingencies’.24  
Thus, there was a shift in anthropological and social scientific approaches to HIV/AIDS where the disease was re-
situated in a broader perspective that included the health and social conditions that structure it.22 
Singer does not examine HIV/AIDS ‘in isolation as a new epidemic with unique features,’ (pg. 993)22 rather he 
examines it in terms of a broader health crisis.  His early work on HIV is still relevant today due to the concept of 
syndemics as a tool to understand the ‘set of synergistic or intertwined and mutual enhancing health and social 
problems facing the urban poor’ (ibid.).  Syndemics examines co-deleterious disease interactions and the 
political, economic, and social contexts in which they are situated.  He argues that urban minority populations 

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suffer disproportionately from underlying conditions (hypertension, cirrhosis, diabetes), preventable diseases 
(STDs, HIV TB), and substance abuse.  The diseases and conditions that comprise an urban syndemic are 
interconnected.  For example, ‘poverty contributes to poor nutrition and susceptibility to infection’; ‘poor 
nutrition, chronic stress, and prior disease’ result in a weakened ‘immune system thus increasing susceptibility 
to new infection’; and, many ‘socio-economic problems and stressors increase the likelihood of substance abuse 
and exposure to HIV’ (ibid).  In applying sydemics Singer challenges (at the time) taken for granted conceptual 
categories that wondered if there was something biological or in the social behaviour of gay or bisexual men and 
IV drug users that was causing this new disease.  However, providing clearly defined and bounded descriptors of 
homosexuality or IV drug use to identify people at special risk or in need of special prevention efforts proved 
complicated and to have many unintended consequences.  These consequences include the perpetuation of 
misunderstandings of who is at risk and how, mistargeting health education, stigmatization, dividing 
communities and reinforcing social divisions, spreading the disease, and concentrating public health resources 
only on AIDS while ignoring the social and syndemic nature of AIDS 22.  Singer illustrates that understanding the 
social construction of AIDS is critical to ‘fighting’ it (ibid.).  This approached, coined by Singer, has shaped much 
of medical anthropology and is taking hold in public and global health.   
The CMA perspective argues that HIV need not be seen as having an existence independent from human activity 
and culture, including political economy, even if it is assumed to be a ‘part of nature’ because ‘nature need not 
be understood from an ahistoric naturalistic perspective’ 22.  Singer has shown us that the study of disease must 
include a wider exploration of the systemic structures in which it is located, the co-deleterious conditions with 
which it interacts, and the social worlds it creates and moves within.  This perspective has now been widely 
adopted and applied to not only the study of HIV/AIDS, but within entire disciplines like anthropology, the social 
sciences, and public health.  We use this theoretical perspective to inform how we study HIV/AIDS more broadly, 
and to how we explore patients’ perceptions and experiences on and of DTG/3TC.  We do this by suggesting that 
not only does disease have a social life, but so do the medicines used to treat them. 
 
Social lives of medicines 
In this research we take medicines to be material things that have ‘biographies’ or social lives as they move 
through different settings and are attributed value as individual things or as commodities for exchange 25.  
Following 26 we are concerned with the social uses and consequences of medicines, specifically DTG/3TC.  
Medicines have relationships ‘with people and between people’ (ibid. 14) and are the ‘most personal of material 
objects’ (ibid. 3) with the power ‘to transform bodies’ (ibid. 5). They ‘can be simultaneously noxious and 
beneficial’ (ibid. 6).  This does not mean that we overlook or ignore the therapeutic functions medicines have 
but building on 27 we intend to draw attention to the aspects of medicines that tend to be overlooked.  This study 
allows us to pay attention to the non-medical meanings and effects of medicines by understanding how DTG/3TC 
means different things and serves different interests to different people in different situations (ibid. 4). 
In undertaking a study of patient perceptions and experiences of DTG/3TC we will explore patients’ own 
rationalities for use of medicines; for example, patients might skip prescribed doses at the weekend when they 
intend to take ‘club drugs’ that negatively interact with their medicine.  This might impact how patients perceive 
or experience the tolerability of a drug- not just in terms of tolerability of side-effects but also tolerability in 
regard to lifestyle.  We will also attempt to understand how patients perceive and experience the efficacy of 
DTG/3TC while accounting for local and individual contingencies that influence efficacy.  What works for one 
person might not work for the next, and different dosages, timings, and ways of taking medicines are tinkered 
with by health care professionals and patients on a case by case basis 28.  Additionally, safety of DTG/3TC must 

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be understood in relation to patient vulnerability, particularly in relation to their own situation.  What we hope 
to show is that to truly explore the study variables (tolerability, efficacy, and safety) we must take medicines to 
be social objects while also locating the study of HIV in broader structures that guide our daily lives. 
In conclusion, we suggest that in adopting this theoretical framework we can best understand the tolerability, 
safety, efficacy, and unmet needs of DTG/3TC not only as defined by biomedical science, but also through an 
understanding of patients’ perceptions and experiences.  Critical Medical Anthropology allows us to factor in 
broader structural issues that might impact patient circumstances and thus influence their perceptions and 
experiences of or on DTG/3TC.  While simultaneously taking medicines to have social lives allows us better to 
understand the relationship individual patients have with DTG/3TC and the ways that patients speak between 
themselves about it.  This will help us to not only provide evidence of patients’ biomedical experiences of 
DTG/3TC, but also the ways they feel and speak about it, and the stories patients’ share with each other about 
it.  Having first-hand patient knowledge of DTG/3TC means ViiV Healthcare can improve their communication of 
the drug and that health care providers and support networks (e.g. Sussex Beacon, Terrence Higgins Trust) can 
improve communication with patients about their treatment and the future of HIV treatment. 
 
4 
RESEARCH QUESTION/AIM(S) 
We have identified two primary research questions: What are patients’ experiences and perceptions of the safety, 
effectiveness, and tolerability of the 2-drug regimen DTG/3TC?  What are the unmet needs of patients undergoing 
the 2-drug regimen?  
To explore patients’ perceptions and experiences of the 2-drug treatment regimen DTG/3TC, including 
potentially unmet treatment needs. 
 
4.1 
Objectives 
 
▪ 
To investigate patients’ perceptions and experiences on the safety, effectiveness, tolerability, and unmet 
needs of the DTG/3TC 2-drug regimen 
▪ 
To conduct comparative analysis of the safety, effectiveness, tolerability, and unmet needs between 
patients on the DTG/3TC 2-drug regimen and patients on other two-drug and three-drug combinations 
▪ 
To provide recommendations 
that improve doctor-patient communication, 
knowledge 
and 
understanding of treatment plan, and additional care that ought to be considered in patient-centred, 
holistic care plans 
 
4.2 
Outcome 
1. To identify patients’ perceptions and experiences on the safety, effectiveness, tolerability, and unmet 
needs of the DTG/3TC 2-drug regimen 
2. To share findings through published articles, at international conferences, and through public 
engagement  
3. To inform the future direction of HIV treatment by providing evidence of patients’ perceptions and 
experiences of 2-drug regimens 
4. To improve doctor and patient communication by identifying patient fears, worries, misconceptions, and 
general concerns of their drug regimen and by providing specific recommendations to improve 
communication during public engagement 
 

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5 
STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYSIS 
 
We will employ a qualitative study design with in-built processes for data analysis so that the study follows an 
iterative process and can be refined after each method.  To generate a robust data set we will utilise three 
methods: cultural domain analysis (CDA), focus group discussions (FGDs), and in-depth interviews.11  
Triangulation of methods will ensure we have a valid and reliable data set that provides nuanced understanding 
of patient perception and experience.  We will conduct all or some of the methods digitally or in person, 
depending on COVID-19 guidance from the UK Government and the University of Sussex; therefore the protocol 
will include a description of both in-person and digital methods and ethics, security and study limitations. 
Digital Research and Platform 
Isolation measures to contain the spread of COVID-19 means that our methods need to be adapted for the 
possibility that in-person interactions must be avoided.  It is also possible that as lockdown measures ease in the 
UK and in-person meetings become allowed that participants prefer to take part in the study remotely and 
online.  Social research has been conducted online for many years and we referred to Lupton (2020) or a 
comprehensive set of resources on how to ‘do’ fieldwork in a pandemic.  
Although interviews and focus group discussions have long been adapted to be conducted online and via 
telephone, to our knowledge, cultural domain analysis has never been conducted from a distance or online.  To 
inform how to adapt this method to online we consulted with the Brighton and Sussex Medical School (BSMS) 
Research Ethics Committee and BSMS Technology Enhanced Learning for guidance on ethics, platform, and 
method.  We conducted a User Acceptance Study of the research methods to ensure they were adaptable and 
could still produce valid and reliable data.  Results of the Study indicate cultural domain analysis can be adapted 
for online implementation and we are currently writing-up findings and recommendations for publication. 
We followed the University of Sussex guidance published by the Research Ethics and Integrity Committee (REIC) 
on the use of video conferencing platforms in research (April 2020).  In the guidance the REIC suggests 
researchers use Microsoft Teams, Microsoft Skype for Business, or Zoom for Education for video conferencing.  
The research for this project is considered ‘highly confidential’ thus we will seek to employ Microsoft Teams or 
Microsoft Skype for Business.  However, when it is not possible or the research participants requests, we will use 
Zoom for Education.   
We will also offer participants the option for us to call them by telephone for participation in CDA and IDIs.  We 
feel this is a viable option to offer based on guidance from David Fray, protocol contributor, and his experiences 
with the HIV community at the Sussex Beacon.  For CDA we will offer to telephone participants while we 
simultaneously log into the shared Padlet page to maintain the visual component of the method. 
To maintain digital security, we will follow the REIC guidance and when possible avoid using the functionality 
built into Teams and Skype for Business to record interviews.  Instead we will use a separate device, like an audio-
recorder, that has a secure password.  When it is not possible to audio-record or the participant prefers to use 
built-in recording functionality we will identify the default location where recordings are stored so they can be 
retrieved and stored securely.  In Microsoft Teams recordings are stored in Microsoft Stream cloud upon which 
we will retrieve the recording and delete it from the cloud.  Zoom for Education and Skype for Business allow for 
recordings to be saved locally on the computer.  Files saved to the computer will be removed and deleted from 
our devices or file location and stored securely in University approved research storage, namely OneDrive.  Files 
will be password protected within a specific folder.  Recordings will be deleted once transcription and note-taking 
are complete. 
Participants will be informed that interviews and focus group discussions will be recorded in the participant 
information sheet shared before the interview.  They will be given the option for the researcher to record using 
built-in recording functionality or audio-recorded using a separate device.  CDA, FDGs and in-depth interviews 
will be audio-recorded, checked for quality, and transcribed verbatim.  Participants will also have the option of 

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whether they could like their camera on or off during CDA, IDIs, and FGDs.  They will be informed of this option 
in the PIS and the RA will confirm their preference in email communication (see 11.12 Appendix 12- Participant 
Email Communication: draft script).   
The research team has consulted with both BSMS ethics and Technology Enhanced Learning (TEL) for advice on 
security, ethics, ease of use, and accessibility.  As a result, specific components of the study like text size and 
colour have been considered for improved accessibility and data outputs. 
Study Design 
This is a qualitative study design with emphasis on an iterative approach.  Each phase of data collection and 
subsequent analysis is iterative, and key to developing insight and meaning into participant experiences and 
perceptions of the variables under study.  30 suggests that qualitative analysis is “a loop-like pattern of multiple 
rounds of revisiting the data as additional questions emerge, new connections are unearthed, and more complex 
formulations develop along with a deepening understanding of the material. Qualitative analysis is 
fundamentally an iterative set of processes”.  Our study design allows for an iterative process where CDA data is 
collected and analysed to identify patterns, themes, and categories.  From these we will refine our interview and 
FGD questions to accommodate what has emerged from the data, rather than imposing frameworks onto 
participants.  
This iterative process allows us to gain deeper insight into the variables under study and to, in turn, make more 
actionable recommendations.  For example, cultural domain analysis will allow us to understand patients’ 
knowledge frameworks regarding tolerability.  We might begin to see a multiplicity in the meaning of tolerability, 
namely that it includes not just the management of drug side-effects, but also the management of treatment 
adherence/the commitment it takes to adhere to a specific regimen.  Tolerability could thus have several levels 
of analysis - tolerability of the drug and tolerability of overall regimen.  This has actionable implications for the 
funder, patient groups, and HIV treatment units because we now have conceptual understanding of what the 
variable tolerability means to patients in certain demographics and how it compares to the meaning prescribed 
by health care providers and pharmaceutical companies.  Thus, when a health care provider asks patients how 
they are coping with the drug the patient may respond that they have minimal side effects.  However, our study 
can provide suggestions for health care providers to probe deeper and perhaps ask how patients are coping with 
adhering to the treatment regimen.  We anticipate we will uncover many linguistic and conceptual misalignments 
that will be actionable for the study stakeholders.  Such insights could allow for better alignment in 
communication and treatment plans, and thus better health outcomes for patients.   
Methods  
Cultural Domain Analysis 
First, Villa, Ackley, and the Research Assistant will conduct cultural domain analysis with 80-120 people (see 
section 7.2.1 for more on how sample size was determined).  Cultural domain analysis is ‘the study of how people 
in a group think about lists of things that somehow go together.  The goal is to understand how people in different 
cultures (or subcultures) interpret the content of domains differently’.12  In this study, cultural domain analysis 
will explore how people living with HIV and on dual or triple therapy treatments think about and interpret of the 
safety, effectiveness, tolerability, and unmet needs of DTG/3TC as compared to their current or previous 
treatments.   
Cultural domain analysis is a type of structured interviewing method that is very productive because it is known 
to be enjoyable to administer, and it is an easy way to collect and analyse data from a large number of people.  
CDA will enable us to understand how participants perceive the factors that influence their treatments.  The 
researchers will analyse the data according to the study variables to gain insight into what needs they have in 
treatment that are currently unmet by analysing for factors that positively or negatively impact unmet needs, as 
well as safety, effectiveness, and tolerability of treatment more generally, and DTG/3TC specifically.  The primary 
variable we intend to explore with CDA is patient unmet need.  Asking respondents to discuss the positive and 

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negative factors related to their treatment will allow us to analyse findings according to unmet need (see 11.4 
Appendix 4 – Sample Cultural Domain Analysis questions and probes).  We feel that analysing the data to 
understand this variable is a better approach than their directly asking patients to list unmet needs.  ‘Unmet 
need’ is an analytical concept that many participants may not directly understand or may depend on the duration 
of their current treatment.  Findings from a User Acceptance Study (UAS) conducted to inform how we adapt 
CDA from in-person to online support this.  In the UAS we asked participants to list the unmet needs they have 
in either their kitchen, bathroom, or workspace.  We found that unmet need was difficult to articulate, 
particularly in comparison to when we asked people to list the positive and negative factors in those spaces.  We 
also found that unmet need was something that could only be realised over time.  This led us to believe that 
patients newly diagnosed and just starting treatment, as well as patients who have recently switched drug-
regimens might not know what their unmet needs are yet.  They might only discover what needs are lacking after 
some time, thus indicating that analysing according to positive and negative factors will better illuminate any 
unmet needs.  Findings from CDA will be further explored in IDIs and FGDs to ensure our analysis is consistent 
with patient experiences and perceptions expressed in other methods. 
Within CDA the researchers will utilise the tools of free listing, pile-sorts, and ranking. When this method is 
conducted in-person we will ask participants to write their answers on notecards.  When this method is 
conducted online, we will utilise Padlet, an application to create an online bulletin board that can be used to 
display information for any topic and if often used in digital learning.  
Free listing is a simple method where participants are asked to list all they know about ‘x,’ and the goal is to get 
informants to list as many items as they can in a domain.  We will first ask the target population to list the most 
important factors that positively/negatively impact their experience on DTG/3TC.  We will ask the control 
population to list what they perceive to be the most positive/negative components of a DTG/3TC regimen (if 
they are unfamiliar with this particular combination then, with dual therapy more generally).  Then, we will ask 
the target population to list the most important factors that positively/negatively impacted their experiences on 
triple therapy or alternative dual therapy combinations before switching to the DTG/3TC regimen.  If the 
participant has only ever been on DTG/3TC, then we will ask them the most important factors that 
positively/negatively impact their current regimen.  We will ask the control population to list the most important 
factors that positively/negatively impact their current dual or triple therapy regimens.  Probing and prompting is 
essential in free listing and will be used carefully as to not guide respondent answers (e.g. ‘are there any more 
you can think of?’).  The discussion will be audio-recorded using a hand-held audio recorder and the free list will 
be either photographed (if conducted in person) or saved as an image (if conducted online).  
Upon completing the free listing, we will ask participants to pile sort, or to ‘put the terms together which they 
feel belong together’.12  This is a simple and compelling method for collecting data about ‘what goes with what’.11  
We will ask participants to put positive/negative factors together according to what they feel belongs together.  
Participants will be asked to describe the rationale for each of the piles created.  The discussion will be audio-
recorded using a hand-held audio recorder and the pile sort will be either photographed (if conducted in person) 
or saved as an image (if conducted online).   
The final part of our cultural domain analysis is to ask participants to rank order their lists.  We will have 
participants rank in order the positive/negative factors that most/least meet their treatment needs and support 
their quality of life while undergoing treatment.  Participants will be asked to describe their rationale for their 
rank ordering.  The discussion will be audio-recorded using a hand-held audio recorder and the rank list will be 
either photographed (if conducted in person) or saved as an image (if conducted online). 
We will use the online tool Padlet to conduct the cultural domain analysis. At the start of the interview each 
participant will be sent a unique and confidential link to a new Padlet page via the chat function in Teams, Skype, 
or Zoom.  The page will be linked to the researcher’s personal data and no personal data will be linked to the 
participant.  Both the researcher and the participant will log into the same Padlet page at the same time.  This 
will allow the researcher to observe the participant list, sort, and rank their domains in real time.  The researcher 

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will export each Padlet board to an image and saved as data for the research team.  At the end of the interview 
the research team will archive the Padlet session so that the board is taken off-line, and data is more secure. 
Focus Group Discussions 
Upon completion of cultural domain analysis Villa, Ackley, Clarke, and the Research Assistant will conduct 
preliminary analysis as part of an iterative approach to data collection and analysis.  We will use initial insights 
gained from this first method to better inform the questions and probes Villa, Ackley, and the Research Assistant 
will ask in 3-6 FGDs with a total of 18-60 people, with 9-10 people per in-person FGD (or fewer depending on UK 
Government Guidance) and 6 people per online FGD (see section 7.2.1 for more on how sample size was 
determined). The difference in FGD group size for in-person versus online is because online FGDs tend to be 
more ‘clunky’ and ‘prone to technology issues, lagging, internet dropouts, and interruptions’ 29. For these reasons 
the literature suggests that it is optimal to cap online FGDs at 6 participants 31–33.  Whether the FGD is in-person 
or online each FGD will have a moderator and a facilitator.  The moderator will be responsible for the 
practicalities of the interview including; audio-recording and note-taking, supporting participants if there is a 
technical issue or if they need to leave the room, keeping track of the digital platform chat box, and letting 
participants into digital platform.  The facilitator is responsible for guiding the discussion, asking questions, 
ensuring participants respect each other, and encouraging all participants to contribute. 
Due to potential patient hesitancy to disclose their status to others in an FGD we are planning for a sample size 
that is variable in number (18-60 participants).  When FGDs are conducted online, participants will be able to 
choose if they want to have their video on or off and if they would like to use a pseudonym.  When FGDs are 
conducted in-person we will use The Sussex Beacon meeting room to facilitate a more comfortable environment. 
Focus group discussions will elicit patient perceptions and experiences of DTG/3TC and their current treatment 
regimen (see 11.5 Appendix 5 – Sample Focus Group Discussion questions and probes).  We will aim to conduct 
2 FGDs with each sample population, thus 2 FGDs with patients currently on DTG/3TC, 2 FGDs with patients on 
an alternative dual therapy regimen, and 2 FGDs with patients on a triple therapy regimen.  In the FGDs with 
patients on DTG/3TC we will elicit patient experiences on the treatment and their perceptions before switching 
to it.  In the FGDs with patients on other dual and triple therapy treatments we will elicit their perceptions of 
DTG/3TC and the future of HIV care and treatment more generally. 
In-depth Interviews 
Upon completion of the FGDs Villa, Ackley, Clarke, and the Research Assistant will, again, conduct a preliminary 
data analysis to refine our in-depth interview questions and probes.  Villa, Ackley, and the Research Assistant will 
conduct 6-12 in-depth interviews with participants on DTG/3TC to elicit patient narratives and treatment 
histories of the regimen (see section 7.2.1 for more on how sample size was determined).  In-depth interviews 
with the target population will allow participants to share specific experiences, fears, hopes, concerns, 
unexpected outcomes, etc. of the DTG/3TC therapy.  We will analyse the interview data according to the  
variables of safety, tolerability, effectiveness, and unmet needs to provide case studies of patient experience.  
We will also conduct 6-12 in-depth interviews with participants on alternative dual therapy treatments, and 6-
12 interviews with participants on triple therapy regimens.  Interviews with the control population will allow us 
to learn about potential misconceptions, misunderstandings, rumours, gossip, knowledge gaps, etc. about 
DTG/3TC from patients on alternative therapies (see 11.6 Appendix 6 – Sample In-depth Interview questions and 
probes).  This insight will help inform our recommendations to health care providers and ViiV Healthcare about 
unmet patient needs and the hopes/fears they may have about the future of HIV treatment; health educatio n 
for patients before they change regimens to DTG/3TC; improved patient care, including potential psycho-social 
support for patients before and during their transition to DTG/3TC. 

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Limitations and benefits of digital methods 
Social research has been conducted online for many years and there are many resources to support and examples 
of using online tools.  We acknowledge that adapting methods that were initially planned for face-to-face use to 
a more ‘hands-off’ mode presents potential limitations and benefits.   
The biggest limitation of adapting CDA to ‘hands-off’ mode is that there are no published resources or examples 
of doing this method online.  After consultation with BSMS Research Ethics Committee and BSMS Technology 
Enhanced Learning we conducted a methodological User Acceptance Study (UAS) to ‘test’ the feasibility of this 
method online.  In the pilot UAS had 21 participants who participated in CDA and provided feedback about their 
experiences and suggestions for improvement.  The pilot included experienced social scientists, clinicians, patient 
representatives, and individuals not familiar with academic research and potentially lacking digital confidence.  
We also invited people with visual impairments, of different generations, and various caring responsibilities to 
imitate potential challenges in conducting the study online. 
Online interviews are different from in-person interviews due to ‘the role of the technology in facilitating real-
time co-presence and interactivity’ and ‘the approach the interviewer takes to build rapport and curate the 
conversation’ 29.  A vast amount of scholarship on how to conduct online interviews 34–36 informed our approach 
to the method; including how to structure an online interview and how to build rapport from a distance.  
Potential limitations include difficulties in assessing body language and building rapport. 
FGDs are unique because of their focus on interpersonal interaction, however the dynamics change when 
conducting them online.  In some cases, online groups can be ‘particularly well-suited’ to deal with sensitive 
topics 37.   
Potential benefits of online research include increased anonymity due to the option to turn one’s camera off or 
use a pseudonym. Additionally, accessing the online venue might be less of a barrier to participation than finding 
time to travel to the research location (ibid.).   
Data Analysis 
Each phase of data collection and subsequent analysis is iterative, and key to developing insight and meaning 
into participant experiences and perceptions of the variables under study. Berkowitz suggests that qualitative 
analysis is “a loop-like pattern of multiple rounds of revisiting the data as additional questions emerge, new 
connections are unearthed, and more complex formulations develop along with a deepening understanding of 
the material.  Qualitative analysis is fundamentally an iterative set of processes”.30  Our study design allows for 
an iterative process where CDA data is collected and analysed to identify patterns, themes, and categories.  From 
these we will refine our interview and FGD questions to accommodate what has emerged from the data, rather 
than imposing frameworks onto participants. 
 
This iterative process allows us to gain deeper insight into the variables under study and to, in turn, make more 
actionable recommendations. For example, cultural domain analysis will allow us to understand patients’ 
knowledge frameworks regarding tolerability.  We might begin to see a multiplicity in the meaning of tolerability, 
namely that it includes not just the management of drug side-effects, but also the management of treatment 
adherence/the commitment it takes to adhere to a specific regimen.  Tolerability could thus have several levels 
of analysis- tolerability of the drug and tolerability of overall regimen.  This has actionable implications because 
we now have conceptual understanding of what the variable ‘tolerability’ means to patients in certain 
demographics and how it compares to the meaning prescribed by health care providers and pharmaceutical 
companies.  Thus, when a health care provider asks patients how they are coping with the drug the patient may 
respond that they have minimal side effects.  However, our study can provide suggestions for health care 
providers to probe deeper and perhaps ask how patients are coping with adhering to the treatment regimen. 
We anticipate we will uncover many linguistic and conceptual misalignments that will be actionable for the 
funder, clinicians, and community organisations.  Such insights could allow for better alignment in 
communication and treatment plans, and thus better health outcomes for patients. 

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Quantitative data from the free listing, pile sorts and ranking will be analysed by Villa, Ackley, and the Research 
Assistant through ANTHROPAC; a program for collecting and analysing data on cultural domains.  The program’s 
analytical tools include techniques that are unique to Anthropology, such as consensus analysis, as well as 
standard multivariate tools such as multiple regression, factor analysis, cluster analysis, multidimensional scaling 
and correspondence analysis.  In addition, the program provides a wide variety of data manipulation and 
transformation tools.  We will conduct proximity analyse to compute measures of similarity and difference 
between respondents on DTG/3TC vs dual therapy vs triple therapy.  We will also conduct consensus analysis to 
evaluate the extent and type of intracultural variability in the sample based on regimen and demographic 
variables. Villa, Ackley, Clarke, and the Research Assistant will summarise our findings from the cultural domain 
analysis by using standard descriptive statistics.  Audio-recordings from FGDs and interviews will be checked for 
quality and transcribed verbatim in English (the language of data collection).  Villa, Ackley, and the Research 
Assistant will code qualitative data in NVivo (version 12) according to standard qualitative analytical practices.12  
Data will then be analysed using applied thematic analysis to identify and describe both implicit and explicit ideas 
within the data.  Applied thematic analysis is a more specific form of thematic analysis, which can be described 
as’ a method for identifying, analysing and reporting patterns (themes) within data’.38 Thematic analysis 
minimally organizes and describes a data set in rich detail through the active role the researcher plays in 
identifying patterns/themes, selecting which are of interest, and reporting describing them in text.38 Applied 
thematic analysis (ATA) ‘is a type of inductive analysis of qualitative data that can involve multiple analytic 
techniques’.39 In ATA the researcher identifies key themes in the data that are transformed into codes (e.g. 
efficacy, tolerability, safety).  Themes can be identified through word searches and data reduction techniques.  
Ultimately, ATA can be used to build theoretical models or to find solutions to real world problems.  Such analysis 
may include comparing code frequencies, identifying code co-occurrence, and graphically displaying 
relationships between codes within the data set.13 
Data Validation 
We will employ several strategies suggested by40 to validate our data.  We will incorporate several 
methodological strategies to ensure the trustworthiness of our findings.  We will account for any personal biases 
which may influence findings through reflexivity in our methods and approach.  We will mitigate sampling bias 
through critical reflection of our recruitment methods at each stage of the research.  We will keep meticulous 
records of our methods, sampling, data, and analysis to demonstrate a clear decision train and ensure 
interpretations of data are consistent and transparent.  We have built in a control group to establish comparison 
cases to seek out similarities and differences across participant accounts.  We will include rich verbatim 
descriptions of patients accounts as data to support findings.  We will demonstrate clarity in terms of thought 
processes during data analysis and interpretations.  In an effort to reduce bias we have built a research team of 
4 people to ensure that variables, methods, and analysis are considered and discussed from several different 
perspectives.  We can incorporate improved methods of validation by inviting participants to comment on their 
interview transcripts and whether the final themes and concepts created adequately reflect the variables under 
investigation.  Finally, we have included data triangulation by including different methods to help produce a more 
comprehensive set of findings. 
Research Integrity 
The integrity of qualitative research can be defined by its trustworthiness, credibility, applicability, and 
consistency.13  All efforts are in place in the design of this study to guaranteed trustworthy results: there is a 
robust and transparent description of the different methods that will be used, and a detailed account of how the 
data will be generated and analysed is provided.  In order to ensure credibility of our findings, the researchers 
will adopt a neutral and non-judgemental approach in conducting the various phases of the study, not to 
influence patients’ reported perceptions; furthermore, all results will be triangulated by the different 
methodologies (i.e. cultural domain analysis, FGDs, in-depth interviews), to further reinforce the validity and 
reliability of the findings.  The rich sample size and the depth of some of the approaches are likely to generate a 

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robust data set.  The HIV cohort in Brighton is largely composed by white men who have sex with men, and 
women and patients of non-white ethnicities represent a minority.  All efforts will be put in place to ensure an 
adequate representation of these minority groups to ensure applicability of the findings in different contexts.  
We will target the Sunflower Clinic for an enriched recruitment of women: the Sunflower Clinic is a service 
available in Brighton dedicated to women living with HIV. 
 
6 
STUDY SETTING 
The study setting will either be online or in person depending on the COVID-19 pandemic, guidance from the UK 
Government and the study sponsor, and research participant preference.  The study will be conducted in person 
in Brighton, United Kingdom, at the Clinical Research Facility at the University Hospitals Sussex NHS Foundation 
Trust for the interviews and at The Sussex Beacon for the FGDs.  Online the study will be conducted via Microsoft 
Teams, Zoom for Education or Skype for business.  Data analysis and write-up will be carried out online with 
video conferencing when appropriate.  Public engagement will be carried out in-person or online, depending on 
the COVID-19 pandemic and guidance from the UK Government and the study sponsor. 
 
Participants accessed in-person will be at a pre-booked meeting room in the Clinical Research Facility at the 
University Hospitals Sussex NHS Foundation Trust or The Sussex Beacon at a time convenient for the participant.  
Participants accessed online will be able to join Team, Zoom, or Skype from a location of their choosing, although 
we will suggest participants have access to reliable internet, a laptop or tablet, and a private space.  Participants 
accessed online can choose whether they would like their device’s camera on or off and they can choose to use 
a pseudonym for anonymity (particularly during FGDs). 
 
The research settings (online and in-person) will provide a confidential and comfortable space for participants to 
take part, both key elements in building rapport.  Rapport is vital to the success of the project as participants 
need to feel safe and comfortable to share their experiences with the researchers.  In-person we will provide 
refreshments and allow the participant to take breaks at any time.  Online the participant can join from the 
comfort of their home, can opt to have the camera on or off, can use a pseudonym, and can take breaks at any 
time. 
 
The same ‘types’ of activities will be carried out at each site with slight variation in implementation.  For example, 
in CDA in-person participants will write answers on index cards and move them around.  Online CDA participants 
will use Padlet to write answers and move them around the screen. 
 
The only site-specific requirement to run the study online is that participants have access to the internet. 
 
7 
SAMPLE AND RECRUITMENT 
7.1  
Eligibility Criteria 
The study population includes participants that are over 18, currently a patient of the HIV Department of BSUH, 
and on one of the therapies from our control or target population.  We also aim to include participants that are 
from underrepresented populations including but not limited to women, minority ethnicity groups, trans-
genders. 
7.1.1 
Inclusion criteria  
Inclusion criteria includes that participants are  
1. adults (aged 18 years old or older),  
2. able to consent,  
3. receive HIV care at the HIV Department of the Brighton and Sussex University Hospital (Lawson Unit/ 
Clinical Research Facility at the University Hospitals Sussex NHS Foundation Trust), and  

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4. on one of the following therapies  
a. control population 
i. Juluca (DTG/rilpivirine[RPV]) 
ii. boosted darunavir plus lamivudine (DRV/r or DRV/c + 3TC) 
iii. boosted darunavir plus raltegravir (DRV/r or DRV/c + RAL) 
iv. a triple regimen (2 nucleos(t)ide reverse transcriptase inhibitors [NRTIs] + 1 InSTI; 2 
NRTIs + 1 non-nucleoside reverse transcriptase inhibitor [NNRTI]; 2 NRTIs + boosted 
protease inhibitor [PI/b]) 
b. target population  
i. DTG/3TC 
5. All genders, sexual orientations, and socio-economic groups are eligible for participation 
7.1.2 
Exclusion criteria  
Patients not fitting the inclusion criteria including those taking off-label drug combinations due to complex HIV 
resistance patterns; ART naïve or individuals declining ART will be excluded.  Patients without access to the 
technology to participate in the online study will be given the option to participate in person (following COVID-
19 guidance), and if this is not possible they will be excluded. 
7.2  
Sampling 
 
This study includes a target and control group through purposive sampling.  We suggest that the variables this study 
sets out to explore (i.e., safety, effectiveness, tolerability, and patient unmet needs) are best understood by including 
a control group. This is because DTG/3TC will not be experienced and perceived in isolation from patient’s previous 
drug regimens or from other patients on different drug regimens.  When a participant on DTG/3TC describes their 
experiences and perceptions they will be making a comparison to a ‘time before’ or to ‘an other’.  For example, we 
anticipate patients to describe current experiences of DTG/3TC effectiveness in comparison to a time they were on 
another drug regimen or in comparison to a friend/known person on another drug regimen (e.g. ‘DTG/3TC is more 
effective than my previous treatment’ or ‘DTG/3TC seems to be less tolerable because my friend is on a different 
regimen and has fewer side effects’). 
 
This indicates we need to explore other drug regimens through a control group so that comparisons that arise in the 
data will have a reference point rooted in data. In short, if a patient says ‘DTG/3TC is more safe than my previous 
treatment’ we can understand not only experiences on DTG/3TC, but also how it compares to other treatments. 
 
However, as the study design is iterative, we will first analyse the CDA data to identify if there is a justifiable 
distinction between initial findings within the control population, namely between the two and three drug regimens.  
If the CDA data reveals unique findings for the two and three drug regimens, then we will continue the study with a 
control group consisting of both two and three drug regimens. If the data does not reveals unique findings within 
the control  group, then the control population for the FGDs and IDIs will be modified to include only patients on 
three-drug regimens while those on alternative two-drug regimens will be excluded. 
 
Additionally, the subjective nature of these variables means that each person will have a different understanding, 
meaning, perception, and experience of the study variables.  The funder, the sponsor, the researchers, and health 
care providers will have one, or more, way of defining the variables, but there is added value in exploring what they 
mean to patients.  By widening our participant population to not just include the target population, but to also 
include the control groups we will gain a more in-depth understanding of what these variables mean to patients.  
This will ensure conceptual and operational alignment of the variables between patients and researchers.  So, when 
we report findings from the study on safety or tolerability, there is conceptual and linguistic alignment. 
 

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The addition of the control group of patients on other dual therapies will allow us to tease out the peculiar 
characteristics of the dual DTG/3TC beyond the mere reduction of molecules employed for the treatment. 
 
7.2.1  
Size of sample 
Out of a total HIV cohort composed by more than 2000 patients at BSUH, there are currently 40 patients on the 
2-drug regimen DTG/3TC.  We will approach all 40 patients on DTG/3TC to participate in the study; however, 
based on previous study recruitment at our centre we anticipate about 20% of those approached to consent.  In 
the cultural domain analysis, we will recruit a minimum of 8 and up to 40 participants from the target population 
and 80-116 participants from the control population for a sample range of 80-120 participants. We aim to 
conduct 1-2 FGDs with each sample group (i.e. DTG/3TC, other dual therapy, triple therapy), with each FGD 
consisting of 6-10 people; thus our FGD sample size will be 18-60 people.  We aim to conduct 6-12 in-depth 
interviews with patients on DTG/3TC, 6-12 interviews with patients on alternative dual therapies, and 6-12 
interviews with patients on triple therapy giving an in-depth interview sample size of 18-36 people.  We will 
approach the same participants for the CDA, FGDs, and in-depth interviews. 
The sample size used in qualitative research methods is often smaller than in quantitative research.  This is because 
qualitative research is most concerned with gaining an in-depth understanding of a phenomenon and is focused on 
meaning, which is centred on the how and why of a particular issue.  In-depth interviews are not necessarily 
concerned with making generalisations to a larger population and do not tend to rely on hypothesis testing but is 
rather a more inductive and emergent process.  As such, the aim of the in-depth interview and FGD data is to create 
analytical, demographic, and ethnographic categories from the data and then to analyse relationships between 
categories while attending to how the lived experience of participants can be understood 41,42. 
We acknowledge there is variability in what is suggested as a minimum sample size for qualitative research, and 
guidance in the literature can range anywhere from 5 to 50 participants 42.  Sample size depends on numerous factors 
including the quality of data, the scope of the study, the nature of the topic, the amount of useful information 
obtained from each participant, and the methods employed 43.   
We intend to follow the principle of data saturation, or when the data collection process no longer offers any new 
or relevant data.  In interviews Guest, et al. found that data saturation often occurs within the first twelve interviews 
while meta-themes might appear after six interviews.44  We apply their findings to the IDI sample size and expect to 
reach data saturation in a variable sample size of 6-12 participants for each sub-group.   In the data analysis process 
we will be transparent about our sample size sufficiency by noting when and by what metrics saturation was reached 
in each method 45.  If the researchers determine that saturation has not been achieved in any particular method, 
then the time period for participant recruitment will be extended to ensure that more data can be collected.   
We acknowledge that participation in all three methods is a large commitment from the participants.  We will 
encourage participants to take part in all three methods, but it is not required.  We aim to recruit all DTG/3TC patients 
in the Lawson Unit, and will target underserved populations from the control groups.  This should allow for a more 
representative sample amongst the entire participant sample. 
Finally, we suggest that through the study design and methods we can achieve validity and reliability in qualitative 
research.  The study design emphasises triangulation of methods (cultural domain analysis, in-depth interviews, 
FGDs), and each method collects different ‘types’ of data.  Cultural domain analysis is a structured interview where 
the same questions will be asked of each participant, while in-depth interviews allow for flexibility in interview 
question probes, while FGDs allow participants to engage with each other and build on group discussion.  Thus, one 
method is highly structured and requires a larger sample, one encourages flexibility and in-depth exploration of 
variables, and the other is based on dialectical processes in group settings.  It is with a combination of methods and 
approaches that we feel confident we will achieve data saturation. 
 
7.2.2  
Sampling technique 

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We will use purposive sampling11 to recruit a diverse population in terms of age, gender, socioeconomic group, 
ART, time on treatment, and number of previous ART regimes; particular attention will be placed on recruiting 
participants from underrepresented groups (i.e. older patients; women; people with history of challenges to 
adherence; people with co-morbidities).  If we struggle to recruit participants through purposive sampling, then 
we will use snowball sampling11 where existing study subjects recruit future subjects from among their networks 
(providing they meet inclusion criteria).   
In purposive sampling, the researchers decide the purpose they want participants (or communities) to serve, and 
they recruit them.  For this study the participants are on a specific drug regimen (DTG/3TC as well as alternative 
two and three drug regiments) and receiving treatment at a specific location (the Lawson Unit).  In purposive 
sampling there is no overall sampling design that determines how many of each type of informant is needed for 
a study, rather the researchers recruit who is available and eligible.  Purposive samples is used widely in (1) pilot 
studies, (2) intensive case studies, (3) critical case studies, and (4) studies of hard-to-find populations11. 
 
7.3 
 Recruitment 
Participants will be recruited through several methods.  The electronic clinical database will be screened and 
potential participants will be identified by members of the study team to be recruited during clinical sessions.  
Additionally, participants will be recruited through peer support groups; exercise, women’s, and online groups 
at the Sussex Beacon; a study flyer for doctors to email or handed directly to their patients and to be circulated 
amongst the aforementioned groups, as well as amongst consultant group, nurses, and by the Research Assistant 
in or around the clinic (see 11.7 Appendix 7 – Participant Recruitment Flyer).  Participants will be recruited 
through: 
• 
Presentations to the Lawson Unit nurses and doctors (in-person or remotely);  
• 
By sharing a digital version of the poster on the TV screen in the Lawson Unit;  
• 
By sharing the flyer with Terrence Higgins Trust in Brighton; 
• 
The Lawson Unit Brighton Sexual Health HIV research webpage; 
• 
Promotion of the project via media channels such as radio stations, online/offline LGBTIQ+ magazines 
and newspapers, websites (e.g. More to Me Than HIV website), and TV channels; 
• 
Attending the Lunch Positive Friday lunch club to share information and recruit participants (this is a 
lunch club offering subsidized meals for people living with HIV. It also offers a once a month dinner for 
PLWH who are over 50, and has just launched a befriending service for PLWH. They often invite guests, 
from charities and health sector, to be available to talk about their work to the meal attendees); 
• 
The Sussex Beacon (it has a Service Users Forum, a Day Service (funded by Social Services), and a Women 
and Families Service, all of which can have invited guests, which can be a useful platform to promote 
interest in PEDAL); 
• 
Peer Action (an organization run for, and by, PLWH; Peer Action organises health and social activities); 
• 
The creation of a PEDAL website; 
Clinical Research Nurses (CRN) will support participant identification and screening through the electronic clinical 
database search (2 hours a week for three months) and time dedicated to check patient eligibility. When 
approaching patients in the Lawson Unit waiting room, our patient representative David Fray will support us as 
a volunteer spending a day a week promoting and recruiting participants for PEDAL in the clinic. 
Participation in the study will either be in-person or digital depending on the COVID-19 guidance.  Participants 
will receive a patient information sheet (see 11.9 Appendix 9 – Participant Information Sheet) and will sign an 
informed consent form (see Appendix 11.10 Appendix 10 – Participant Informed Consent).  Additionally, a 
participant recruitment poster (see 11.8 Appendix 8 – Participant Recruitment Poster) will be on the check-in 
desk in the HIV Department of the BSUH with information on the study and on how to become involved.  If 
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conducted phone consultation.  If patients are interested in learning more about the study the clinician will 
obtain oral consent for the patient to be contacted by email with a digital participant information sheet and 
consent form. 
It is our hope that clinical members of the research team will draw on existing patient-doctor relationships to 
make potential participants feel safe and comfortable in their deliberations of whether to consent.  We have 
specific consent procedures in place that ensure there is no coercive element as patients may be in a dependent 
relationship with their doctors.  These include obtaining consent at several stages of the study (for each method); 
through different means (oral, written, and informally through emails to set up digital meetings); and with 
different members of the RT (the research assistant, CA or GV) in addition to the initial recruitment approaches 
through doctors, nurses, etc.  We also hope that positive patient-researcher interactions in the cultural domain 
analysis will help build rapport with potential FGD participants and make them feel comfortable to participate.   
For both in-person participation a member of the research team will contact the participant by phone or email 
to schedule a day and time at the participant’s convenience.  Participants based in Brighton will be reimbursed 
for any travel costs incurred in travel to and from BSUH.   
We also acknowledge that there are practical limitations to the study and we are hopeful that the study design will 
facilitate greater participant involvement for two reasons.  First, we are offering participants a £10 voucher for their 
participation in each of the three methods (up to £30 if they take part in all of them), and we will also reimburse 
them for their transport to/from the hospital for study participation.  Participants will be given a Love2Shop voucher 
card. Participants will also receive tea/coffee and will be able to suggest a time that works best for them.  These 
accommodations may make potential participants more likely to participate.  Additionally, the researchers have built 
rapport with patients in the Lawson Unit and the patient representative has built rapport with patients who are part 
of the Sussex Beacon network.  This existing trust will help facilitate higher participation rates.  Second, the methods 
selected allow participants to share experiences and feelings that they may not normally get the chance to express 
to health care professionals.  The research provides a different platform for dialogue than participants might be used 
to and we hope this will appeal to them. 
We will try to boost recruitment numbers for cultural domain analysis, and all methods, through the help of the HIV 
consultants and research nurses at the Lawson Unit and the Clinical Research Facility at the University Hospitals 
Sussex NHS Foundation Trust, patient representatives at the Sussex Beacon, information flyers posted and 
distributed at the Lawson Unit and the Clinical Research Facility at the University Hospitals Sussex NHS Foundation 
Trust, and on digital media.  The research nurses will have access to patient information upon check-in and can screen 
for study eligibility without violating patient confidentiality.  The research nurses will provide the patient with a study 
information sheet and a study researcher will approach the patient to obtain verbal consent that they would like to 
learn more and potentially participate (see 11.11 Appendix 11- Verbal Consent Checklist).  If they consent the 
researcher will take the patient to a separate area and describe the study more in-depth and take informed consent 
before organising a day/time to conduct the methods.  We hope that this approach will ensure we can reach data 
saturation. 
7.3.1 Sample identification 
Participants will be identified through purposive sampling by the research team with the help of several recruitment 
strategies.  The first way we will identify participants is through a database screening in the Lawson Unit to determine 
eligible patients that clinicians and nurses can contract.  Secondly, the patient’s existing clinical care team will have 
access to patient records without explicit consent in order to identify potential participants, and to check whether 
they meet the inclusion criteria or before making the initial approach to patients.  If the patient meets inclusion 
criteria the clinical care team will share recruitment materials and the participant information sheet. 
Participants will be recruited publicly through several methods: (1) David Fray will share recruitment materials with 
his network at the Sussex Beacon and researchers will determine if participants are eligible to participate, (2) 
recruitment materials will be shared in the Lawson Unit reception and website, Brighton LGBTQ+ magazines, and 
the Brighton Terrence Higgins Trust and researchers will determine if participants are eligible to participate.   

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If a patient is identified by the clinical care team or through the public methods the referral process involves patients 
contacting the research team directly via the contact information provided on the recruitment materials and the 
participant information sheet.  Additionally, the clinical care team can provide the contact information of the 
participant to the research team upon oral consent on behalf of the potential participant to be contacted. 
If patients attend interviews or FGDs in-person they will be compensated in the form of vouchers as explained before. 
 
7.3.2 Consent 
The study involves several stages consent, including oral and fully informed consent.  If participants are identified 
through a database screening by a member of the healthcare team, then they will seek oral consent via 
telephone, email, or in-person at the patient’s next appointment to contact them with further information about 
the study.  If participants are identified by the clinical care team during a clinic visit, then the clinical care team 
will obtain oral consent from the potential participants that we can contact them via telephone or email with 
further information about the study.  If participants contact the research team directly, then we will first obtain 
oral consent to follow up regarding eligibility to participate. 
Once participants have orally agreed to participate in an eligibility screening or for us to follow up with further 
information about the study we will begin the process of obtaining fully informed consent.  We will communicate 
with participants in person, via email or telephone to inform them that we will provide them with a participant 
information sheet and an informed consent form for them to read, consider, and to ask us any questions about.  
We will then give participants the participant information sheet and an informed consent form either in person 
or send it over email.  In the text of the email participants will be informed that they can ask any questions in 
email or we can phone them to answer any questions.  Participants will be expected to return the signed and 
dated consent form before proceeding to the next phase. 
Once the signed and dated consent form is received the research team will store it securely along with the 
participants preferences for the research to be in-person or online, for their preferred digital platform, whether 
they would like to have their video camera on or off, and whether they would like to use a pseudonym in any 
FGDs.  These preferences will be obtained through oral or written communication with the research team prior 
to participation, but after consent has been obtained.   
Prior to any CDA, FGDs, and IDIs the researcher conducting the interview or FGD will obtain oral consent to 
ensure the participant read and understood the participant information sheet and informed consent form.  The 
participant will also have an opportunity to ask any remaining questions before participation in the method.  The 
researcher will also conduct an assessment for capacity according to the guidelines that a capable person will: 
• 
understand the purpose and nature of the research  
• 
understand what the research involves, its benefits (or lack of benefits), risks and burdens  
• 
understand the alternatives to taking part  
• 
be able to retain the information long enough to make an effective decision. 
• 
be able to make a free choice  
• 
be capable of making this particular decision at the time it needs to be made (though their capacity may 
fluctuate, and they may be capable of making some decisions but not others depending on their 
complexity) 
• 
where participants are capable of consenting for themselves but are particularly susceptible to coercion, 
it is important to explain how their interests will be protected 
Participants will be invited to join all components of the research; however, they may choose to take part in only 
the first method, the first and second method, or all three methods. Both written (either in-person or by email) 
and oral consent (in-person or on the digital platform, both audio-recorded) will be obtained before participation 
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If participants take part in more than one method, then both informed written consent and oral consent will be 
taken prior to each method.  This means if a participant takes part in all three methods we will have a written 
and oral consent form for the CDA, a separate written and oral consent form for the FGD, and a separate written 
and oral consent form for the IDI. 
 
8 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
Ethical approval will be sought from the NHS REC ethical committee.  All documents will be approved by the 
University’s Sponsorship Sub-Committee (SSC). Patients will provide informed consent prior to enrolment either 
in person or through a document emailed to participants prior to each method.  Participants will be asked to 
provide verbal consent before the start of each method.  All members of the Research Team will complete 
training on Good Clinical Practice. 
There are also the added ethical considerations of conduct research during a pandemic and the ‘affective 
atmospheres’ created ‘when normal routines are disrupted and many people feel uncertain or worried, or are ill 
or caring for ill family members’ (pg. 20).29 However, people may be ‘more confined, feeling bored or restless but 
in good health’ and ‘may welcome the opportunity to be part of a research project’ (ibid.). 
Participants will be able to stop the interview or FGD at any time and they will be free to leave.  They will have 
the right to withdraw their consent or use of data collected at any time, upon which participant data will be 
destroyed (in the case of an FGD participant their responses will be deleted from audio recordings and 
transcripts).  If participants exhibit distress or become upset during data collection the researcher will ask if they 
would like to pause or stop the interview or FGD.  Participants will not have to answer any question they do not 
want.  All data will be stored on password-protected computers and will be encrypted.  
 
8.1 
Assessment and management of risk 
The research activities might illuminate several health-related issues; including the possibility that participants 
are not adhering to treatment regimens or that they are engaging in risky behaviour.  It is also possible that the 
research might reveal that participants are suffering from poor physical, mental or social well-being and that is 
manifested through physical symptoms, low mood or social insecurities.  In anticipation of these potential 
circumstances the research team will provide the name, contact information, and location of outreach services 
on the participant information sheet given to all participants at the time of consent.  Additionally, the research 
team will encourage participants to speak with their clinician.  Any potential risks to participants are 
communicated in the Participant Information Sheet. 
 
8.2  
 Research Ethics Committee (REC) and other Regulatory review & reports 
Before the start of the study a favourable opinion will be sought from the Health Research Authority (HRA) (NHS 
Research Ethics Committee - REC). The Ethics Committee will have reviewed the present protocol, the patient 
information sheet, the consent form, and the advertisement used.  All correspondence with the Research Ethics 
Committee will be retained and added as appendices to the study protocol. 
Substantial and non-substantial amendments will be presented to the HRA.  Only substantial amendments will 
be additionally considered by the NHS REC and will not be implemented until that review is in place and other 
mechanisms are in place to implement at site. 
The Chief Investigator will produce an annual report (APR) for the REC and HRA and will notify them at the end 
of the study.  The APR will be submitted to the REC within 30 days of the anniversary date on which the favourable 
opinion was given, and annually until the study is declared ended.  If the study is ended prematurely, the Chief 

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Investigator will notify the REC, including the reasons for the premature termination.  Within one year after the 
end of the study, the Chief Investigator will submit a final report with the results, including any 
publications/abstracts, to the REC. 
 
Regulatory Review & Compliance 
Before enrolment of patients into the study, the Chief Investigator/Principal Investigator or designee will ensure 
that appropriate approvals from participating organisations will be in place.  For any amendment to the study, 
the Chief Investigator or designee, in agreement with the sponsor will submit information to the appropriate 
body in order for them to issue approval for the amendment.  The Chief Investigator or designee will work with 
the site (R&D departments at NHS sites as well as the study delivery team) so they can put the necessary 
arrangements in place to implement the amendment to confirm their support for the study as amended. 
 
Amendments  
Amendments to the protocol will be submitted by the Chief Investigator to the University of Sussex Sponsorship Sub-
Committee for review and approval.  If deemed substantial by the Sponsor, the proposed amendment will be 
submitted to the Health Research Authority.  Once approved, the protocol will be updated with the amendments in 
a newer version. 
 
8.3  
Peer review 
The protocol will be reviewed internally by all members of the study team (G. Villa, C. Ackley, A. Clarke, D. Fray); 
by the Joint Clinical Research Office of the University of Sussex (D. Coton); by the Head of Department of Global 
Health and Infection of the Brighton and Sussex Medical School (M. Newport);  by the lead research nurse of the 
Clinical Research Facility at the University Hospitals Sussex NHS Foundation Trust (L. Barbour), and by ViiV 
Healthcare (G. Hilton-Smith).  External reviewers are A. Parkhurst (medical anthropologist at the University 
College London) and R Tan (social scientist at National University of Singapore). 
 
8.4  
Patient & Public Involvement 
The study includes one/two patient representative(s) whose roles are described according to the INVO Patient 
and Public Involvement briefing.46  Patient representatives have helped adapt in-person methods to online by 
taking part in a User Acceptance Study and providing feedback.  They have reviewed and commented on the 
study protocol.  They will help recruit participants from their professional networks.  They will facilitate and 
support public engagement activities at the end of the study.  Their role will be independent from the Sponsor 
and Investigators as they represent patients and the Sussex Beacon. 
 
8.5 
Protocol compliance 
Accidental protocol deviations will be documented in dedicated forms, filed, and reported to the Chief 
Investigators and the Sponsor. 
 
8.6 
Data protection and patient confidentiality  
All investigators and study site staff will comply with the requirements of the Data Protection Act (2018) with 
regards to the collection, storage, processing and disclosure of personal information and will uphold the Act’s 
core principles.  Participant’s identifying information will be replaced by an unrelated unique sequence of 

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characters (a combination of letters and numbers) to guarantee anonymisation.  A reconciliation list will be 
created and stored in a locked cabinet with the study protocol at the Clinical Research Facility at the University 
Hospitals Sussex NHS Foundation Trust, whereas the anonymised data collected via the audio-recording of the 
FGDs and the IDIs (recordings and transcripts), and the images from the CDA, will be saved in a folder in the 
University of Brighton OneDrive.  G. Villa, C. Ackley, A. Clarke and the Research Assistant will have access to the 
data.  The Chief Investigator will be the data custodian.  The data will be stored for the entire duration of the 
study until publication of the main findings and for a maximum duration of 12 months after its conclusion.  All 
data will be subsequently destroyed. 
 
8.7 
Indemnity 
The University of Sussex has indemnity insurance in place to cover its legal liabilities for this study. 
 
8.8 
Access to the final study dataset 
G. Villa, C. Ackley, the Research Assistant, and A. Clarke will have access to the complete dataset, including the 
recordings of the FGDs and the IDIs, and the images and notes from the CDAs.  Access to the appropriate sections 
of the dataset will be also granted to the MSc students engaging in some aspects of their research project for 
their MSc dissertation.  All audio-recordings, images, and notes will be saved in a password-protected electronic 
folder, saved in the University of Brighton OneDrive. 
 
 
9 
DISSEMINIATION POLICY 
 
9.1  
Dissemination policy 
The main findings of the study will be written up and submitted to a HIV journal (e.g., AIDS and Behavior).  A 
critical exploration of unmet patient needs and/or patient perceptions of the future direction of HIV research 
will be submitted to a journal at the intersection of anthropology and health (e.g., Social Science and Medicine).  
Both journals have the option to publish open access, which we have budgeted for appropriately.   The main 
findings of the study be also made available at international conferences and on university repositories.  Findings 
will be available to participants and the NHS Trust.  Findings will be also shared in public engagement through 
the Sussex Beacon and Brighton and Sussex Medical School.   
9.2  
Authorship eligibility guidelines and any intended use of professional writers 
Villa, Ackley, Clarke, Fray, and the Research Assistant will form the core of the research team and will be granted 
authorship in the publication of all the manuscripts arising from this research.  First authorship and senior 
authorship of the manuscripts reporting the main findings will be shared between Villa and Ackley according to 
the nature of the publication (clinical vs social science/anthropology).  Additional researchers will be granted 
authorship according to their role and input in keeping with the guidelines with the International Committee of 
Medical Journal Editors.  Master students from the MSc of Global Health at the Department of Global Health and 
Infection will be invited to engage in the research and explore themes of their interest emerging from the CDA, 
FGDs and/or IDIs, such as stigma, for their Master dissertation.  First authorship will be granted to the students 
if their results will lead to a separate publication. 
 

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