STI Prophylaxis and Emergence of Antimicrobial Resistance
Conditions: Sexually Transmitted Infection (STI) Prevention, Antibiotic Prophylaxis, Antibiotic Resistance, Bacterial, Microbiome, Doxycycline
Sponsor: University College, London

SPEAR, EDGE (Sponsor) number 174194, IRAS 330315, Protocol, 1.1, 16/DEC/2024  
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n  
 
 
 
 
 
 
 
 
FULL TITLE OF THE STUDY 
STI Prophylaxis and Emergence of Antimicrobial Resistance 
SHORT TITLE/ACRONYM 
SPEAR 
PROTOCOL VERSION AND 
DATE 
V1.1 [16/DEC/2024] 
SPONSOR 
University College London (UCL) 
SPONSOR REFERENCE 
NUMBER (EDGE) 
174194 
FUNDER(S) 
British Infection Association (BIA), British HIV Association 
(BHIVA), National Institute for Health and Care Research 
(NIHR)  
IRAS NUMBER 
330315 
CHIEF INVESTIGATOR 
Dr Manik Kohli MBChB MSc MRCP 
Doctoral Research Fellow, Institute for Global Health, UCL 
CO-INVESTIGATORS 
Prof Nigel Field, Institute for Global Health, UCL 
Dr John Saunders, Institute for Global Health, UCL  
Dr Oliver Stirrup, Institute for Global Health, UCL  
Prof Samuel Sheppard, Dept of Biology, University of Oxford 
Dr Odile Harrison, Nuffield Dept of Population Health, 
University of Oxford 
 
 
 
 

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PROTOCOL VERSION HISTORY 
 
Version 
Stage 
Versions 
Number 
Version Date 
Protocol updated 
& finalised by; 
Reasons for Update 
 
1.0 
21/NOV/2024 Dr Manik Kohli 
 
Current 
1.1 
16/DEC/2024 
Dr Manik Kohli 
Response to REC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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DECLARATIONS 
The undersigned confirm that the following protocol has been agreed and accepted and that 
the investigator agrees to conduct the study in compliance with the approved protocol and 
will adhere to the U.K. Policy Framework for Health and Social Care Research 2017 (3rd 
edition) (as amended thereafter), the EU General Data Protection Regulation (2016/679) 
and the UK Data Protection Act (2018), Sponsor SOPs and applicable Trust policies and legal 
frameworks. 
 
I (investigator) agree to ensure that the confidential information contained in this document 
will not be used for any other purposes other than the evaluation or conduct of the research 
investigation without the prior written consent of the Sponsor. 
 
I (investigator) agree to ensure that no research activity or recruitment will commence at 
participating research sites until the appropriate regulatory approvals and NHS 
confirmations of Capacity and Capability have been issued, and Sponsor green light 
confirmed. 
 
I (investigator) 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.  Any deviations from 
the study as planned in this protocol will be explained and reported accordingly. 
 
Chief Investigator:  
 
Signature: ....................................................................................      Date: 21/NOV/2024 
Print Name (in full): ........Manik Kohli........... 
Position: ...........Doctoral Research Fellow...................................... 
 
On behalf of the Study Sponsor: 
 
 
Signature:  
Date: 07/11/2024 
Print Name (in full): PUSHPSEN JOSHI 
Position: RM&G MANAGER- UCLH& UCL JRO 
 
 
 
 
 
 
 
 
 

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STUDY SUMMARY 
 
IDENTIFIERS 
IRAS Number 
330315  
REC Reference No. 
24/EM/0282 
Sponsor Reference No. 
174194 
Other research 
reference number(s)  
UCL Data Protection: Z6364106/2023/09/15 
ClinicalTrials.gov registration *insert*  
Full (Scientific) title 
STI Prophylaxis and Emergence of Antimicrobial Resistance 
Health condition(s) or 
problem(s) studied 
Antibiotic prophylaxis for bacterial sexually transmitted 
infections; antimicrobial resistance; gut and throat 
microbiomes 
Study Type 
Observational 
Target sample size 
108 
STUDY TIMELINES 
Study Duration/length 
28 months 
Expected Start Date 
January 2025 
End of Study date 
April 2027 
Key Study milestones 
 
03/2023 Funding awarded (British Infection Association) 
08/2023 Funding awarded (British HIV Association) 
05/2024 Funding awarded (NIHR) 
01/2025 Aim for REC approval; Study site setup 
01/2025 Recruit first participant 
07/2025 Recruit final participant 
07/2026 Final participant final follow-up visit  
04/2027 NIHR funding ends; Complete study 
FUNDING & OTHER 
Funding 
National Institute for Health and Care Research (NIHR) 
Doctoral Fellowship £589,590 (NIHR303717); British Infection 
Association (BIA) £10,000 (2023/Manik Kohli); British HIV 
Association (BHIVA) £9,979.96 (BHIVA/5020/2023/Kohli) 
STORAGE of SAMPLES / DATA (if applicable) 
Human tissue samples 
Stool samples and oropharyngeal swabs. Collected and 
temporarily stored at the study site (Central and North West 
London NHS Foundation Trust). Study samples transferred to 
collaborating institution for processing and storage 
(Department of Biology, University of Oxford, South Parks 
Road, Oxford, OX1 3RB). Samples and extracted bacterial DNA 
will be stored at the Department of Biology, University of 
Oxford) for the duration of the study. 
Data collected / Storage 
Pseudonymised questionnaire responses will be stored at UCL 
KEY STUDY CONTACTS 
Chief Investigator / 
Principal Investigator 
Dr Manik Kohli 
Email: m.kohli@ucl.ac.uk, manik.kohli@nhs.net  
Telephone: 07837837096 
Clinical Project Manager 
Dr Emmi Suonpera 

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Email: e.suonpera@ucl.ac.uk 
Telephone: 0203 108 2081 
Other relevant study 
personnel 
Prof Nigel Field – Co-investigator; Primary Supervisor 
Dr Odile Harrison – Co-investigator; Supervisor 
Dr John Saunders – Co-investigator; Supervisor 
Dr Oliver Stirrup – Co-investigator; Statistician; Supervisor   
Prof Samuel Sheppard – Co-investigator; Supervisor 
Prof Richard Gilson – Head of Research Centre 
Prof Magnus Unemo – Collaborator  
 
 
KEY ROLES AND RESPONSIBILITIES 
 
SPONSOR: The sponsor is responsible for ensuring before a study begins that arrangements 
are in place for the research team to access resources and support to deliver the research as 
proposed and allocate responsibilities for the management, monitoring and reporting of the 
research. The Sponsor also must be satisfied there is agreement on appropriate 
arrangements to record, report and review significant developments as the research 
proceeds, and approve any modifications to the design. 
 
FUNDER: The funder is the entity that will provide the funds (financial support) for the 
conduction of the study. Funders are expected to provide assistance to any enquiry, audit or 
investigation related to the funded work. 
 
CHIEF INVESTIGATOR (CI): The person who takes overall responsibility for the design, 
conduct and reporting of a study. If the study involves researchers at more than once site, 
the CI takes on the primary responsibility whether he/she is an investigator at any particular 
site. 
 
The CI role is to complete and to ensure that all relevant regulatory approvals and 
confirmations of NHS Capacity and Capability are in place before the study begins. Ensure 
arrangements are in place for good study conduct, robust monitoring and reporting, 
including prompt reporting of incidents, this includes putting in place adequate training for 
study staff to conduct the study as per the protocol and relevant standards. 
 
The Chief Investigator is responsible for submission of annual reports as required. 
The Chief Investigator will notify the REC and JRO of the end of the study (including 
the reasons for premature termination, where applicable). Within one year after the 
end of study, the Chief Investigator will submit a final report with the results, 
including any publications/abstracts to the REC and JRO. 
 
PRINCIPLE INVESTIGATOR (PI):  Individually or as leader of the researchers at a site; 
ensuring that the study is conducted as per the approved study protocol, and report/notify 
the relevant parties – this includes the CI of any breaches or incidents related to the study. 
 
 
 

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KEY WORDS 
Sexually transmitted infections; STI; antibiotic prophylaxis; antimicrobial resistance; 
microbiome. 
 
LIST OF ABBREVIATIONS 
 
 
AE 
Adverse Event 
AMR 
Antimicrobial Resistance 
AR 
Adverse Reaction 
BHIVA 
British HIV Association 
BIA 
British Infection Association 
CI 
Chief Investigator 
CNWL 
Central and North West London NHS Foundation Trust 
CRO 
Contract Research Organisation 
DMC 
Data Monitoring Committee 
DSH 
Data Safe Haven 
HCP 
Health Care Provider 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
MMC 
Mortimer Market Centre 
MSM 
Men who have sex with men 
MTA 
Material Transfer Agreement 
NHS 
National Health Service 
NIHR 
National Institute for Health and Care Research 
PI 
Principle Investigator 
PIS 
Participant Information Sheet 
PEP 
Post-exposure Prophylaxis 
PPI(E) 
Patient and Public Involvement (and Engagement) 
PrEP 
Pre-exposure Prophylaxis 
QA 
Quality Assurance 
QC 
Quality Control 
R&D 
Research and Development 
REC 
Research Ethics Committee 
SAR 
Serious Adverse Reaction 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SHS 
Sexual Health Service 
SOP 
Standard Operating Procedure 
SSI 
Site Specific Information 
STI 
Sexually Transmitted Infection 
TMF 
Trial Master File 
WS 
Workstream 
 
 

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CONTENTS 
STUDY SUMMARY ...................................................................................................................... 4 
1 
INTRODUCTION ............................................................................................................. 10 
2 
BACKGROUND AND RATIONALE ................................................................................... 10 
3 
AIM AND OBJECTIVES ................................................................................................... 13 
3.1 
Primary Objective .................................................................................................. 13 
3.2 
Secondary Objectives ............................................................................................ 13 
4 
STUDY DESIGN & METHODS OF DATA COLLECTION..................................................... 14 
4.1 
Study Design .......................................................................................................... 14 
4.2 
Study Timeline ....................................................................................................... 14 
4.3 
Sample Size ............................................................................................................ 14 
4.4 
Visit Activities and Samples ................................................................................... 15 
5 
STUDY SCHEDULE .......................................................................................................... 18 
6 
ELIGIBILITY CRITERIA ..................................................................................................... 18 
6.1 
Inclusion Criteria .................................................................................................... 18 
6.2 
Exclusion Criteria ................................................................................................... 18 
7 
RECRUITMENT ............................................................................................................... 18 
7.1 
Clinic-based: Patients attending CNWL SHS .......................................................... 18 
7.2 
Community-based online ...................................................................................... 19 
8 
CONSENT ....................................................................................................................... 20 
9 
DATA ANALYSIS ............................................................................................................. 21 
9.1 
Statistical Analysis ................................................................................................. 21 
9.2 
Bioinformatic Analysis ........................................................................................... 21 
10 
PATIENT AND PUBLIC INVOLVEMENT (PPI) .................................................................. 22 
10.1 
PPI for Funding Proposals and Study Design ......................................................... 22 
10.2 
Community Advisory Group .................................................................................. 23 
10.3 
Collaboration with The Love Tank ......................................................................... 23 
11 
FUNDING AND SUPPLY OF EQUIPMENT ....................................................................... 23 
12 
DATA HANDLING AND MANAGEMENT ......................................................................... 23 
13 
MATERIAL/SAMPLE TRANSPORT AND STORAGE .......................................................... 26 
14 
PEER AND REGULATORY REVIEW ................................................................................. 26 
15 
ASSESSMENT AND MANAGEMENT OF RISK ................................................................. 27 
16 
RECORDING AND REPORTING OF EVENTS AND INCIDENTS ......................................... 28 
16.1 
Personal Data Breaches ......................................................................................... 28 
16.2 
Adverse Events and Serious Adverse Events Sponsor Reporting Requirements .. 28 
16.3 
Incidental Findings in Research ............................................................................. 29 
16.4 
Protocol deviations and notification of protocol violations .................................. 29 
16.5 
NHS Serious Incidents and near misses ................................................................. 29 
16.6 
Complaints from research participants ................................................................. 29 
17 
MONITORING AND AUDITING ...................................................................................... 30 
18 
TRAINING ...................................................................................................................... 30 
19 
INTELLECTUAL PROPERTY ............................................................................................. 30 
20 
INDEMNITY ARRANGEMENTS ....................................................................................... 31 
21 
ARCHIVING .................................................................................................................... 31 
22 
PUBLICATION AND DISSEMINATION ............................................................................. 31 
23 
REFERENCES .................................................................................................................. 32 

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24 
APPENDICES .................................................................................................................. 33 
24.1 
Associated Documents .......................................................................................... 33 
 
 
Ensure to click ‘update table’ prior to finalising the Protocol 
 
 
 

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1 INTRODUCTION 
 
STI prophylaxis is the use of antibiotics before sex (pre-exposure-prophylaxis, or PrEP) or 
after sex (post-exposure prophylaxis, or PEP) to prevent acquisition of bacterial sexually 
transmitted infections (STIs). There is growing evidence that men who have sex with men 
(MSM), particularly MSM using HIV-PrEP or living with HIV, are buying antibiotics online to 
take as STI prophylaxis.[1,2] This is not currently endorsed by the British Association for 
Sexual Health and HIV (BASHH) or UK Health Security Agency (UKHSA), citing concerns about 
antimicrobial resistance (AMR) although new guidelines are in preparation and will likely 
recommend STI prophylaxis for some patient groups.[1] Recent trials demonstrated efficacy 
of doxycycline-PEP (commonly called ‘DoxyPEP’) in preventing chlamydia, syphilis, and 
gonorrhoea.[3,4] There is a need to understand the AMR risks to inform UK clinical guidance 
and STI prophylaxis implementation. Among MSM, high incidence of antibiotic resistant 
infections, altered microbiomes linked to sexual behaviours and living with HIV, and dense 
overlapping sexual networks, raise concerns about the possible impact of long-term 
antibiotic use. This study will develop the methodology needed to evaluate AMR emergence 
and microbiome changes in MSM who are using STI prophylaxis through bacterial genomics. 
These data will also inform further research on STI prophylaxis, AMR epidemiology, and 
microbiomes and subsequently clinical and public health decisions on STI prophylaxis. 
2 BACKGROUND AND RATIONALE 
 
Rates of bacterial STIs have been rising for the last decade and MSM are disproportionately 
impacted by STIs, particularly antibiotic resistant STIs. [5,6] This poses a serious public 
health threat and represents an increased burden on NHS sexual health services (SHS). 
Novel approaches are needed to halt and reverse these trends. HIV-PrEP provides an 
established, safe, and effective model for biomedical interventions to prevent STIs. There is 
growing interest in STI prophylaxis with small but significant numbers self-sourcing 
antibiotics, and very high levels of acceptability (up to 84%) among MSM if shown to be safe 
and effective.[7,8,9] There are concerns about the risk of AMR development in commensal 
and bystander organisms, as well as the impact on gut and other microbiomes. A debate is 
ongoing in the UK and elsewhere on the introduction of doxycycline-PEP for populations 
with high STI incidence where evidence of efficacy exists.[10,11]  As MSM continue to self-
source antibiotics for STI prophylaxis, and implementation by the NHS in the UK is planned – 
robust AMR and microbiome outcome data will be necessary to understand the risks and 
inform surveillance. 
 
Efficacy of doxycycline prophylaxis 
In 2022, the DOXYPEP randomised controlled trial (RCT) from the USA provided strong 
evidence for the efficacy of doxycycline-PEP to reduce bacterial STI incidence when taken 
within 72 hours of condomless sexual contact.[4] The study found a 65% reduction in STI 
incidence per quarter (RR0.35 (95%CI 0.27-0.46)), with significant reductions in gonorrhoea 
(Neisseria gonorrhoeae), chlamydia (Chlamydia trachomatis) and syphilis (Treponema 
pallidum) incidence among MSM and transgender women (TGW) on HIV-PrEP or living with 
HIV.[4] At study baseline tetracycline resistance among N.gonorrhoeae isolates was 20%, 
which limits generalisability to the UK where it is significantly higher (62%).[12] The French 

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DOXYVAC study of doxycycline-PEP and meningococcal B vaccine found significant 
reductions in chlamydia or syphilis (aHR0.17 (0.12-0.26)) and gonorrhoea (aHR0.67 (0.52-
0.87)) with doxycycline-PEP.[4] Smaller RCTs from the USA, France and Canada also 
demonstrated efficacy of doxycycline-PEP and daily doxycycline-PrEP in reducing incidence 
of chlamydia and syphilis in MSM.[13-15] In 2023, a modelling study examined different 
doxycycline-PEP strategies, such as targeting all MSM/TGW, HIV-PrEP users, or only people 
with multiple STIs diagnosed.[16] Use of doxycycline-PEP in individuals with concurrent or 
repeated STIs could substantially reduce subsequent STIs.[16] However, an RCT in Kenya in 
cisgender women found doxycycline-PEP did not reduce incident bacterial STIs, which the 
study investigators believed to be adherence related.[17] 
 
Use and acceptability 
Surveys from the UK, Netherlands, and Australia estimate STI prophylaxis use among MSM 
using HIV-PrEP or living with HIV to be 3%-10%.[2,7,18] There was also very high levels of 
acceptability of STI prophylaxis among MSM (up to 84%).[8,9] Of concern is that up to 40% 
of STI prophylaxis users report using non-doxycycline antibiotics, such as azithromycin.[2] In 
recent survey by CNWL and UCL, we found that STI prophylaxis users continued to use non-
doxycycline antibiotics, despite increased awareness and discussion about ‘doxycycline-PEP’ 
(Saunders, Kohli and Suonpera, unpublished). 80% of respondents (n=440) in this survey 
were ‘somewhat’ or ‘very likely’ to use doxycycline-PEP/PrEP if deemed safe and effective. 
 
AMR 
There are concerns about further development of AMR in MSM sexual networks that 
already have high rates of STIs with AMR.[12] Unregulated use of self-sourced antibiotics is 
a particular concern. Doxycycline (a tetracycline antibiotic) is needed as first-line treatment 
for STIs such as chlamydia, syphilis, and Mycoplasma genitalium, as well as respiratory, skin, 
and other infections. Overall, data on AMR associated with doxycycline prophylaxis from 
trials remains very limited, or focuses on specific organisms (Staphylococcus aureus, 
Escherichia coli, and Neisseria species); with no clear conclusions on AMR or the impact 
long-term doxycycline-PEP has on human microbiomes, although further analyses are 
expected.[3,4,15] In DOXYPEP, tetracycline resistant N.gonorrhoeae was higher in the 
doxycycline-PEP arm (38%) than at baseline (27%) and in the standard of care (SOC) arm 
(12%).[3] Additionally, although S. aureus carriage was lower in the doxycycline-PEP arm, a 
higher proportion had doxycycline resistance (16%) compared to SOC (8%).[3] In DOXYVAC, 
there was more high-level tetracycline resistance among incident gonorrhoea infections 
with resistance in the doxycycline-PEP arm (33.3%) compared to SOC (18.9%).[4] 
 
Beyond standard microbiological approaches, including in the doxycycline-PEP/PrEP RCTs, 
there are limited data on genetic determinants of AMR in MSM. A study using residual rectal 
swab samples from MSM attending SHS in London estimated prevalence of the mphA gene 
(conferring azithromycin resistance) at 32.5%, and higher still (41.3%) among MSM with a 
diagnosed bacterial STI in the preceding 12 months.[19]  
 
Microbiomes 
The impact of sexual behaviour and HIV on the gastrointestinal and oropharyngeal 
microbiota is of increasing interest.[20-22] Several studies identified differences in the gut 
microbiota between MSM and men who exclusively have sex with women, and sexual 

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behaviour and antibiotic exposure (given differences in STI risk, testing, and treatment) are 
important potential confounders when studying microbiomes in MSM and people living 
with HIV.[18] It has also been suggested that both macrolides and tetracyclines have greater 
impacts on gastrointestinal microbiota compared to other antibiotics.[19] Moreover, 
alterations in gastrointestinal microbiome have been associated with metabolic, mental 
health and autoimmune diseases.[23,24] An oropharyngeal microbiome study noted that 
prevalence of select AMR genes (‘resistome’) was lower in the general population compared 
to MSM (ratio 0.41(0.26-0.65)), but found no difference when comparing MSM with and 
without recent antibiotic exposure.[25] This small cross-sectional study did not assess 
antibiotic STI prophylaxis and was limited by the lack of data on sexual behaviour including 
oral sex and ano-oral sexual contact.[25] Microbiome disturbances are multifactorial and 
differences in the gastrointestinal and oropharyngeal microbiota require careful 
interpretation as findings may be confounded by sexual behaviour and living with 
HIV.[22,27] Despite this, a systematic review of human gut resistome studies included no 
discussion on the potential impact of sexual behaviour or HIV. [26] 
 
 
While the evidence of STI prophylaxis efficacy in MSM is compelling, given the lack of data 
on AMR, global differences in baseline AMR, and the potential addition of long-term 
antibiotic prophylaxis as a recommended STI prevention strategy in MSM, further research 
is required in the UK on the risks associated with STI prophylaxis and methods for 
monitoring and mitigation, such as enhanced surveillance. This research will provide data to 
fill important evidence gaps and develop the methodologies for further AMR research and 
optimised surveillance. 
 
 

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3 AIM AND OBJECTIVES 
 
Research Question 
What are the risks of AMR and microbiome impacts of antibiotic prophylaxis for sexually 
transmitted infections (STI prophylaxis) in MSM, and how can we evaluate and mitigate 
these risks? 
 
Aim 
To evaluate AMR and microbiome changes through bacterial genomics, and generate UK-
based evidence to inform clinical and public health decisions on STI prophylaxis, future AMR 
research, and AMR surveillance. 
 
3.1 Primary Objective 
To assess feasibility and acceptability of detecting AMR emergence and microbiome changes 
in the gastrointestinal tract and oropharynx of MSM who use antibiotic STI prophylaxis 
through bacterial genomics. 
 
3.2 Secondary Objectives 
A) To assess feasibility and acceptability of recruiting STI prophylaxis users via sexual 
health clinics versus online and obtaining appropriate samples. 
B) To evaluate the use of shotgun metagenomic sequencing to identify AMR genes or gene 
mutations conferring resistance to tetracycline and other relevant antibiotic classes. 
C) To evaluate the use of shotgun metagenomic sequencing to identify bacteria present in 
the gastrointestinal tract and oropharynx of MSM. 
D) To estimate the prevalence of AMR genes/gene mutations of interest and describe 
changes over time in the gastrointestinal tract and oropharynx of MSM using and not 
using STI prophylaxis. 
E) To characterise the gastrointestinal and oropharyngeal microbiomes and describe 
changes over time in MSM using and not using STI prophylaxis.  
F) To develop the methodology for future AMR research and surveillance in MSM and 
other relevant population groups. 
 
 

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4 STUDY DESIGN & METHODS OF DATA COLLECTION 
4.1 Study Design 
 
Study design: Molecular epidemiology cohort study 
 
Study site: Central and North West London (CNWL) NHS Foundation Trust Sexual Health 
Services (SHS). CNWL is one of the largest SHS in London, providing HIV PrEP to ~300 MSM 
each month, and routine care for ~3,000 MSM living with HIV. 
 
Study population: MSM aged ≥ 18 years. Target of 108 participants, with minimum 40 
participants living with HIV1, distributed evenly across three antibiotic exposure groups at 
enrolment: 
- 
Group A (n=36): recent2 and recurrent3 doxycycline STI prophylaxis use.  
- 
Group B (n=36): recent2 history of STI treatment with doxycycline. 
- 
Group C (n=36): no recent2 use of any antibiotic for any indication. 
1 40 study places will be ring-fenced for MSM living with HIV, split evenly across the three 
groups (12-13 per group). 
2 recent is defined as within last 3 months. 
3 recurrent is defined as 2 or more doses taken. 
 
Eligible individuals meeting the criteria for group A and B, will be allocated to group A. 
 
4.2 Study Timeline 
See Section 5 Study Schedule for more information on study visits. 
 
End of study: The end of the study is defined as once all study visits for every participant 
have been completed, all study samples processed and undergone bacterial genomic 
sequencing, and data has been checked and locked. Data analysis will be ongoing at the end 
of the study. 
 
4.3 Sample Size 
Target sample size 108. This assumes an overall prevalence of AMR in the gut of 32.5%.[19] 
Under this assumption, the proposed sample size for this study will allow the prevalence of 
Aim for REC Approval  
Jan 2025 
Study site R&D approval and site setup 
Jan 2025 
Recruitment (Visit 1) window 
Jan 2025 – Jul 2025 
Sample processing starts 
Oct 2024 
Follow-up visit 2 window 
Apr 2025 – Jan 2026 
Visit 1 samples bacterial genomic sequencing & analysis 
Jul 2025 – Sep 2025 
Follow-up Visit 3 window  
Oct 2025 – Jul 2026 
Last participant last study visit   
Jul 2026 
Sample processing end  
Jul 2026 
Visits 2 & 3 sample sequencing & complete analysis 
Jul 2026 – Apr 2027 

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AMR genes of interest across all study participants to be estimated with 95% confidence 
intervals (CI) +/- 8.85%. The prevalence within the groups of 36 will be possible to estimate 
with 95%CI +/- 15.5%. This precision will be sufficient to inform the feasibility of larger AMR 
surveillance research and programmes in the same patient population. In each group of 36 
participants, it is expected to observe 11 cases of AMR, with 99% probability of observing at 
least six cases in each subgroup. This will allow piloting all aspects of specimen processing, 
genome sequencing, data processing and transfer workflows. 
4.4 Visit Activities and Samples 
There are 3 planned visits for this study (see Section 5 Study Schedule). All data and samples 
will be pseudonymised. A unique identifier (participant ID) will be assigned to each 
participant enrolled in the study. The participant ID will be used for sample labelling and 
questionnaire completion. All study activities and procedures will be undertaken after 
eligibility has been confirmed and informed consent has been given (see Sections 6 Eligibility 
Criteria and 8 Consent for more details).  
 
At each of the study visits the following three steps will be undertaken: 
 
Step 1: Questionnaire 
Participants will self-complete an electronic questionnaire. This will be pseudonymised using 
the participant ID number, and obtain information on demographics, medical history, sexual 
activity, STI prophylaxis use, any other antibiotic use, and travel. This will be completed on a 
tablet or computer in a private clinic room with a member of the research team on hand in 
case of difficulty or queries. Where possible, the questionnaire incorporates validated 
questions from other research surveys. It will take approximately 15 minutes to complete. 
 
Step 2: Oropharyngeal Swab 
An oropharyngeal swab will be collected from participants by the member of the research 
team conducting the study visit. Prior to collecting each sample, the researcher will ask the 
participant for consent to proceed. All samples will be taken in a private clinic room. The 
swabs will be labelled with the date of collection, the participant ID, and a sample ID 
number.  
 
Step 3: Stool Sample  
Participants will be provided with a stool sample collection kit. For Visit 1, the kit will be 
provided during the study visit or posted to the participant prior to the visit if they have 
completed e-consent (see Section 8 Consent). Kits will include instructions on how to collect 
a stool sample and gloves for the collection. The researcher will explain the process of stool 
sample collection to the participant at the study visit or by telephone if collecting prior to 
the visit.  
 
Participants will be offered a range of options for collecting stool samples: 
• In clinic at study visit: participants providing stool samples during the study visit will 
be directed to a toilet to collect their own sample.  
• At home after study visit: participants will be able to provide a stool sample 
collected at home within 7 days of the study visit and return the sample to the study 
site within 48 hours of collection.  

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• At home before study visit: 
o Visit 1: participants completing e-consent and opting to be posted a stool 
sample collection kit will collect the sample at home less than 48 hours 
before the study visit and to bring it with them.  
o Visits 2 and 3: At Visit 1, participants will be given kits for follow-up visits to 
take home and return when they attend for Visits 2 and 3. Participants will be 
asked to collect the sample at home less than 48 hours before the visit.  
 
Stool samples will be labelled with the date of collection, the participant ID, and a sample ID 
number. 
 
Sample Storage and Transport 
Samples will be labelled with the date of collection, unique participant ID, and a sample ID 
number. Samples will be stored at the study site at -80C for a maximum of 28 days, before 
being couriered in an appropriate container for microbiology samples to the University of 
Oxford laboratory (Department of Biology, University of Oxford, South Parks Road, Oxford, 
OX1 3RB) for processing and storage until the end of the study (see Figure 1 and Section 13 
Material/Sample Storage and Storage). No study samples will be stored beyond the end of 
the expected study completion of April 2027. 
 
Sample Processing and Sequencing 
Sample specific microbial DNA extraction kits will be used. Extracted bacterial DNA will be 
stored at the Department of Biology, University of Oxford at -80C prior to metagenomic 
sequencing. Library preparation and metagenomic sequencing will be undertaken at UCL 
Genomics (20 Guildford Street, London, WC1N 1DZ).  
 
Participants will remain in the study for a maximum of 13 months (360 +/ 30 days) (see 
Section 5 Study Schedule)  
 
 

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5 STUDY SCHEDULE 
 
All study visit activities will be conducted by a member of the clinical research team 
(research doctor, research nurse, or research assistant). For information on identification of 
potential participants and informed consent please see sections 7 Recruitment and 8 
Consent. Participants receive a £30 voucher for each study visit. This will be given to 
participants at the end of each study visit. Participants will be able to withdraw from the 
study at any time. All data and samples collected prior to this will be retained by the 
research team.  
 
Visit 
Schedule 
(days) 
Activities 
Length 
(minutes) 
1 
0 
Informed consent; questionnaire; oropharyngeal 
swab; stool sample 
60 
2 
180 +/- 30 
Questionnaire; oropharyngeal swab; stool sample 
30-60 
3 
360 +/- 30 
Questionnaire; oropharyngeal swab; stool sample 
30-60 
6 ELIGIBILITY CRITERIA 
6.1 Inclusion Criteria 
- 
Aged ≥ 18 years. 
- 
Identifies as a man (cis or trans). 
- 
Has sex with men. 
- 
Able to provide informed consent. 
6.2 Exclusion Criteria 
- 
Use of an antibiotic other than doxycycline in the 3 months prior to enrolment 
- 
Currently being treated for an STI with doxycycline 
- 
Use of doxycycline within the prior 3 months for an indication other than STI 
treatment or STI prevention.  
7 RECRUITMENT 
 
Participant identification and recruitment will be through two distinct methods: clinic-based 
and community-based. The recruitment strategy has been co-developed with the SPEAR 
study community advisory group (see Section 10 PPI). The study includes online community-
based recruitment through targeted adverts on social media and MSM-focused geospatial 
networking (‘dating’) apps to ensure the recruitment target for MSM using STI prophylaxis 
(group A) is met and allow recruitment of MSM not regularly attending in-person SHS or 
living outside London. Enrolment will be monitored in real-time to ensure targets for each 
antibiotic exposure group and MSM living with HIV are achieved.  
 
7.1 Clinic-based: Patients attending CNWL SHS 
Clinician referral 

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Clinicians seeing potentially eligible patients will refer them to the research team. The 
patient will be given the leaflet and PIS to read. If they wish to proceed and are eligible, they 
will be asked to provide informed consent (see Section 8 Consent) and booked for Visit 1 
(see Section 5 Study Schedule). 
 
Direct approach by the research team 
Clinic appointment lists will be screened in advance by a member of the research team for 
potentially eligible participants. Members of the research team are also members of the 
clinical team involved in routine sexual health and HIV care alongside research. Patients will 
be contacted in advance of their appointment or approached in the waiting room. They will 
be given a copy of the PIS to read. If they wish to proceed and are eligible, they will be asked 
to provide informed consent (see Section 8 Consent) and booked for Visit 1 (see Section 5 
Study Schedule). 
 
Participant self-referral 
Posters and leaflets describing the study will be available in clinical areas. These will include 
details of the study specific UCL webpage and contact details for the research team. Patients 
will be able to directly contact the research team by email. They will be sent the PIS to read. 
If they wish to proceed and are eligible, they will be asked to provide informed consent (see 
Section 8 Consent) and booked for Visit 1 (see Section 5 Study Schedule). 
 
These recruitment strategies are used successfully for other studies within CNWL. 
Participation in the study does not impact the routine NHS sexual health or HIV care being 
provided to the participant by CNWL. Study visits and study sample collection are conducted 
independently of routine NHS care provided. The poster/leaflet have been co-designed by 
the community advisory group (see Section 10 PPI). 
 
A log will be kept of potential participants approached in clinic but who decline to 
participate, alongside a reason for declining if given.  
 
7.2 Community-based online 
Social Media 
Social media posts promoting the study will be shared on social media. This will include 
approved images/graphics and recruitment video. A study specific X™ account (formerly 
Twitter™) will be created to promote the study. Posts will also be shared on existing social 
media accounts (e.g. X™, Instagram™) associated with the UCL research team and CNWL. 
The research team have established links with professional organisations (e.g. BASHH) and is 
collaborating with the LGBTQ+ health focused community group The Love Tank who will 
promote the study.  
 
MSM-focused geospatial networking (‘dating’) apps 
Paid adverts will be placed on MSM-focused dating apps (e.g. Grindr, Scruff). This 
recruitment strategy is used successfully for cross-sectional surveys of MSM conducted by 
UCL. 
 

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Online posts/adverts will include a brief overview of the study, information on 
reimbursement for participation, and details of how to contact the research team. Online 
posts/adverts have been co-designed by the community advisory group (see Section 10 PPI). 
Individuals who contact the research team will be sent the PIS and then receive a phone call 
to discuss the study further and assess eligibility. If they wish to proceed and are eligible, 
they will be asked to provide informed consent (see Section 8 Consent) and booked in for 
Visit 1 (see Section 5 Study Schedule). 
 
8 CONSENT 
 
Informed consent will be gained from participants before any study activities are 
undertaken. Participants will be given and/or emailed the PIS to read prior to being asked to 
give informed consent. Participants will have three options for providing informed consent 
using the latest approved informed consent form (ICF): 
1. E-consent prior to the first study visit. 
2. E-consent at the start of the first study visit. 
3. Written consent on paper ICF at the start of the first study visit. 
 
E-consent will be provided using an online REDCap form. Completed e-consent forms will be 
stored in a study specific REDCap database within the UCL Data Safe Haven (see Section 12 
Data Handling and Management) 12.[28] Participants opting for e-consent prior to the first 
study visit will receive a telephone call from a member of the research team (research 
doctor, research nurse, research assistant) to explain the study, confirm eligibility, and 
answer any questions. They will then be emailed a link to the e-consent form to complete 
and sign. The e-consent form will be signed by the member of the research team taking 
consent. 
 
Participants opting to provide informed consent at the start of the first study visit will be 
offered to complete an e-consent or a written consent form. During the informed consent 
process, the study will be explained, participants will be given time to read the PIS again, 
and all questions will be answered. Participants opting for e-consent will complete the form 
online. The e-consent form will be signed by the member of the research team taking 
consent. Participants opting for written paper consent will sign two paper copies of the ICF.  
The person taking consent (research doctor, research nurse, research assistant) will also sign 
both ICFs. One signed ICF copy will be given to the participant and the second copy will be 
retained and stored securely at the study site (CNWL). A scanned copy of the written or e-
consent form will be uploaded to the participant’s CNWL-held medical records. 
 
It will be clearly stated that the participant is free to withdraw from the study at any time 
for any reason without prejudice to current or future care, without affecting their legal 
rights, and with no obligation to give the reason for withdrawal. Participants will be 
informed that if they withdraw from the study, any study samples and data already 
collected will be retained and used in the final analysis. Participants will be asked for specific 
consent to review their study site medical records. 

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9 DATA ANALYSIS 
 
9.1 Statistical Analysis  
The planned statistical analysis is summarised here. The statistical analysis will be fully 
outlined in a statistical analysis plan (SAP). The SAP will be written by Dr Manik Kohli (Chief 
Investigator) and Dr Oliver Stirrup (Co-Investigator & Statistician). The SAP will be finalised 
before any analysis takes place. An analysis of baseline samples will be undertaken once all 
participants have completed Visit 1.  
 
Sample characteristics, STI prophylaxis use, and questionnaire responses will be described 
using absolute numbers and proportions. A pooled prevalence estimate with 95% CI for 
AMR genes/gene mutations of interest will be produced. Chi-square tests will be used to 
evaluate evidence of differences in prevalence between subgroups, although findings will be 
presented with caution given the relatively small sample size. The association between 
detection of AMR genes/gene mutations of interest with demographic and sexual history 
variables will be described and investigated in exploratory univariable analyses.  
 
Descriptive analyses of AMR detection over time within each group will be conducted. If 
adequate variation within individuals over time, then generalised estimating equations 
logistic regression will explore trends over time and consistency of AMR detection within 
each group.  
 
Statistical analyses will be undertaken on the statistical programmes STATA and R.  
9.2 Bioinformatic Analysis 
The bioinformatic methodology and analysis is summarised here. The bioinformatic analysis 
will be fully outlined in a bioinformatic analysis plan (BAP). The BAP will be written by Dr 
Manik Kohli (Chief Investigator) and Prof Samuel Sheppard (Co-Investigator & 
Bioinformatician). 
 
Bacterial taxonomic profiling will use both de novo assembly and read-mapping approaches. 
De novo assembly tools (e.g., MEGAHIT, metaSPAdes) will allow evaluation of taxonomy and 
AMR genetic diversity. Supervised binning methods will group assembled contigs (DNA 
sequences) by species using tools such as metaBAT, and the PubMLST/metaMLST reference 
databases which hosts assembled whole genome sequence data from over 480,000 
bacterial isolates. Antibiotic resistance databases (e.g., Comprehensive Antibiotic Resistance 
Database) will be used to identify genes conferring resistance to tetracyclines (e.g., tet(M), 
tet(W), tet(Q)) and other important antibiotic classes (e.g., Macrolides mphA, ermF).  
 
To mitigate potential assembly problems from low-abundance organisms, read mapping 
approaches will be undertaken using the pipeline CCMetagen which uses the National 
Centre for Biotechnology Information (NCBI) database as reference. Computationally 
intensive analyses will be carried out in a single in silico system that archives and integrates 
bacterial metagenomes and AMR genes with other rich metadata, and can organise and 
share genomes to allow integrated analyses and modelling.  
 

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Genome-wide association study analyses incorporating machine learning will identify core 
and accessory genome AMR elements (including plasmids) from complex samples. Genomic 
variation identified will include gene presence and absence; gene orthologs/alleles; 
insertions/deletions and single nucleotide polymorphisms (SNPs). These will be linked to 
AMR and other metadata. 
 
Bacterial genera diversity (microbiome profiles) and AMR genes/gene mutations of interest 
(‘resistome' profiles) will be compared between baseline study groups, and over time by use 
of doxycycline prophylaxis. Exploratory analysis of microbiome profiles by other 
characteristics including HIV status and sexual history will be undertaken.  
 
This study does not analyse human DNA. 
10 PATIENT AND PUBLIC INVOLVEMENT (PPI) 
 
10.1 PPI for Funding Proposals and Study Design 
Input was sought from: 
- 
The Love Tank, who undertake advocacy work on LGBTQ+ health issues and provide 
information on STI/HIV prevention through their PrEPster and queerhealth.info 
programmes. 
- 
The Terrence Higgins Trust and BASHH lay research panel. 
- 
NIHR Research Design Service lay reviewers.  
- 
Gay and bisexual men, through two workshops with six community members, 
funded by an NIHR PPI grant. 
 
Overall, feedback was extremely supportive of the research and participants were clear that 
this was an important topic.  
 
Changes made to the study on the advice of the PPI groups included: 
- 
Revision of the research objectives to include changes in microbiome over time. 
- 
Mechanisms to ensure ongoing PPI involvement in the study.  
- 
Recruitment: dual strategy from sexual health clinics (to increase likelihood of 
participating) and online (to ensure inclusion opportunities for participants not 
attending clinics and from a wider geographical area).  
- 
Study documents, promotional materials, and dissemination: to include clear 
understandable information about AMR, to use sensitive language to avoid 
contributing to stigma, and for information on STI prophylaxis should be balanced 
discussing both benefits and risks 
- 
Co-production and collaboration: inclusion of co-production group and collaboration 
with trusted community organisations (see below). 
- 
Stool samples: Collection of stool samples in clinic was acceptable, with provision 
options for participants to collect samples at home if they unable to provide a 
sample in clinic. 
 

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10.2 Community Advisory Group 
The study includes a community advisory group. The group will meet regularly throughout 
study (online and/or in-person); and includes patients and community members. To date, 
the group have given input on the PIS and questionnaire; co-designed the online 
adverts/poster; and co-developed the recruitment strategies (see Section 7 Recruitment). 
Throughout the study, the group will monitor enrolment and advise on recruitment 
strategies as needed; co-analyse questionnaire data; co-develop dissemination plans; review 
the overall study findings; and co-produce community-focused outputs. 
 
10.3 Collaboration with The Love Tank 
The Love Tank is an LGBTQ+ and sexual health focused community organisation which runs 
the community programmes PrEPster and queerhealth.info. The Love Tank will be involved 
with online study promotion for community-based recruitment and community 
dissemination of the study findings. 
 
11 FUNDING AND SUPPLY OF EQUIPMENT 
The study funding has been reviewed by the UCLH/UCL Joint Research Office and deemed 
sufficient to cover the requirements of the study.  
 
The research costs for the study have been supported by the National Institute for Health 
and Care Research (NIHR) Doctoral Fellowship £589,590 (NIHR303717), the British Infection 
Association (BIA) £10,000 (2023/Manik Kohli), and the British HIV Association (BHIVA) 
£9,979.96 (BHIVA/5020/2023/Kohli). 
 
12 DATA HANDLING AND MANAGEMENT 
The study is compliant with the requirements of General Data Protection Regulation 
(2016/679) and the UK Data Protection Act (2018). All investigators and study site staff will 
comply with the requirements of the General Data Protection Regulation (2016/679) with 
regards to the collection, storage, processing and disclosure of personal information, and 
will uphold the Act’s core principles. UCL is the data controller; the UCL Data Protection 
Officer is data-protection@ucl.ac.uk. The data processors are Central and North West 
London NHS Foundation Trust.  
 
The project will collect data on age, gender, ethnicity, sexual orientation, sexual history, and 
medical history as part of the research. Data will be collected through participant 
questionnaires and medical records.  Figure 2 below summarises the study team 
organisation and data flow.  
 
All participants will be assigned a unique pseudonymised identifier (participant ID). 
Questionnaire responses and all study samples will be pseudonymised using this participant 
ID. Questionnaire responses will be collected via a secure REDCap form and all data will be 
stored in a REDCap database within the UCL Data Safe Haven.(28) The UCL Data Safe Haven 

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is a secure and protected environment for storing, handling, and analysing sensitive or 
identifiable data.(28) The collection of medical and sexual history information is necessary 
for the aims of the research. Only members of the research team will have access to the 
database. Participants opting for e-consent, this will be completed using a REDCap form and 
stored with the study specific REDCap database within the UCL Data Safe Haven.  
 
This research is a collaboration between UCL and the University of Oxford. Study samples 
collected at the study site will be labelled with the participant ID, sample ID number, and 
date of collection. No identifiable information will be shared outside the study site (Central 
and North West London NHS Foundation Trust, CNWL). A collaboration agreement covering 
material and data transfers will be in place between UCL and the University of Oxford. 
Bacterial genomic sequencing will take place at UCL Genomics. If additional metagenomic 
sequencing of bacterial DNA samples occurs at a third-party organisation (not UCL or 
University of Oxford), a separate MTA will be instituted for the transfer. 
 
Genomic data will be stored at the University of Oxford in line with their data protection 
and data management policies. Pseudonymised questionnaire responses with only 
participant ID numbers will be securely transferred to the University of Oxford for analysis 
alongside the bacterial genomic data. A data flow diagram is included below (Figure 2). 
 
A site agreement will be in place between UCL and the study site (CNWL). For participants 
opting for written paper consent, signed paper consent forms will be stored the study site. A 
copy of the consent form (paper or e-consent) will be uploaded to the participant’s CNWL-
held medical records. A secure password protected log will be kept at the study site which 
will include participant ID numbers alongside identifiable information: name, date of birth, 
medical records number, and contact information (phone number and/or email). This will be 
stored separately to the questionnaire responses at the study site on NHS computers. 
Contact information will be needed to arrange follow-up visits and to invite participants to 
dissemination events at the end of the study. 
 
Data will be retained until the end of study and for up to 20 years (see Section 21 Archiving). 
 

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13 MATERIAL/SAMPLE TRANSPORT AND STORAGE 
 
Stool samples and oropharyngeal swabs will be collected from patients in accordance with 
the patient consent form and patient information sheet and shall include all tissue samples 
or other biological materials and any derivatives, portions, progeny or improvements as well 
as all patient information and documentation supplied in relation to them.  Samples will be 
processed, stored and disposed in accordance with all applicable legal and regulatory 
requirements, including the Human Tissue Act 2004 and any amendments thereafter, and 
the applicable HTA Codes of Practice Departmental SOPs will be followed to facilitate 
regulatory compliance. 
 
Samples will be labelled with the unique participant ID, a sample ID number, and date of 
collection. Study site sample collection, storage and storage SOPs will be written by Dr 
Manik Kohli (CI/PI). Samples will be stored at the study site in a freezer (lowest temperature 
-80C) for a maximum of 28 days, before being couriered in an appropriate container for 
microbiology samples to the University of Oxford laboratory (Department of Biology, 
University of Oxford, South Parks Road, Oxford, OX1 3RB) for processing and storage at -80C 
until the end of the study. Samples will be processed as quickly as possible after collection 
and courier. An MTA will be in place prior to any sample collection and transfer. A study 
specific laboratory SOP, adapted from existing local SOPs and DNA extraction kit protocols, 
will be written by Dr Manik Kohli (Chief Investigator) and Dr Odile Harrison (Co-Investigator 
and Microbiologist) prior to any sample processing. No study samples will be stored beyond 
the end of the expected study completion of April 2027 and will be destroyed in line with 
local health and safety protocols. 
 
Samples will be processed at the University of Oxford, Department of Biology laboratory. 
Samples will undergo bacterial DNA extraction. Extracted bacterial DNA will be stored at the 
University of Oxford Department of Biology at -80C prior to metagenomic sequencing. 
Metagenomic sequencing will be undertaken at UCL Genomics (20 Guildford Street, London, 
WC1N 1DZ).   
 
14 PEER AND REGULATORY REVIEW 
 
The study has been peer reviewed in accordance with the requirements outlined by UCL.  
 
Choose either (having discussed with the UCLH/UCL Joint Research Office): 
 
The Sponsor considers the procedure for obtaining funding from National Institute for 
Health and Care Research, NIHR to be of sufficient rigour and independence to be 
considered an adequate peer review. 
 
The study was deemed to require regulatory approval from the following bodies REC 
Favourable Opinion and HRA Approval). Before any site can enrol patients into the study, 

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the Chief Investigator/Principal Investigator or designee will ensure that the appropriate 
regulatory approvals have been issued, and NHS Confirmations of Capacity and Capability 
and Sponsor green lights are in place. 
 
For any amendments 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 sites (R&D 
departments as well as the study delivery team) to confirm ongoing Capacity and Capability 
for the study. 
 
All correspondence with the Sponsor, REC and HRA will be retained.  The Chief Investigator 
will notify the Sponsor and REC of the end of the study. 
 
It is the Chief Investigator’s responsibility to produce the annual progress reports when 
required; an annual progress report (APR) will be submitted to the Sponsor and REC within 
30 days of the anniversary date on which the favourable opinion was issued, and annually 
until the study is declared ended. 
 
If the study is ended prematurely, the Chief Investigator will notify the Sponsor and 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 Sponsor and to the REC and HRA. 
 
15 ASSESSMENT AND MANAGEMENT OF RISK 
This is a minimal risk observational study. The following potential risks have been identified 
and strategies to mitigate these potential risks are outlines below.  
 
Potential risk 
Emotional distress related to questionnaire completion.  
Plan to minimise this risk 
To minimise this risk, questions have been adapted from validated sources such as the 
National Survey of Sexual Attitudes and Lifestyles (Natsal) and other UCL-sponsored surveys, 
which have been developed with extensive user feedback to be acceptable and easily 
understood. PPI input and feedback has been sought on the questionnaire to ensure 
questions are appropriate and inclusive. If any participants are distressed on questionnaire 
completion, they will be signposted to appropriate support. 
 
Potential risk 
Loss of confidentiality. 
Plan to minimise this risk 
All data will be pseudonymised, with each participant being assigned a unique identifier to 
be recorded on all questionnaires and samples. Study-specific data will be captured 
electronically using a computer or tablet. The data management system for these will be 
based on a mature, secure web application REDcap. All data will be stored in the UCL Data 
Safe Haven. A study log linking the participant ID with the clinic medical records number will 

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be kept securely on NHS computers at the study site (CNWL). Only members of the study 
site research team will have access to the password protected study log and patient 
identifiable information. These will be stored separately on NHS computers and can only be 
accessed by the relevant person(s) on the study research team. All email correspondence 
with potential and enrolled participants will be via NHS email. 
 
Potential risk 
Contamination of clean surroundings when collecting a stool sample. 
Plan to minimise the risk 
Participants will be provided stool sample collection kits. Kits will include how to collect a 
stool sample safely and correctly. Kits will also include gloves for collection of the sample.  
 
Potential risk 
Discomfort from oropharyngeal swabbing 
Plan to minimise the risk 
All member of the research team will undertake training on oropharyngeal swab collection 
to minimise discomfort. 
16 RECORDING AND REPORTING OF EVENTS AND INCIDENTS 
All events and incidents (and near misses) that occur to participants and/ or staff that are 
unexpected and directly related to the research study will be reported to the Sponsor via 
research-incidents@ucl.ac.uk or UCL REDCAP incident reporting form) and host sites via 
their Trust reporting systems, and documented in the Trial Master File/Investigator Site File 
via study-specific incident logs (and related correspondence). This will be completed by the 
CI or PI. The Sponsor will be responsible for investigating, reviewing, or escalating to a 
serious breach if required. 
 
16.1 Personal Data Breaches 
Any personal data breaches will be immediately reported to the UCL Information Security 
Group (ISG) and the UCL Data Protection Officer [data-proection@ucl.ac.uk], (as per form 
and guidance: https://www.ucl.ac.uk/data-protection/guidance-staff-students-and-
researchers/practical-data-protection-guidance-notices/report-breach ), and to the Sponsor 
via the UCL REDCAP incident reporting form 
(https://redcap.slms.ucl.ac.uk/surveys/?s=NE5dypTdFo). The following information will be 
provided: full details as to the nature of the breach, an indication as to the volume of 
material involved, and the sensitivity of the breach (and any timeframes that apply). Sites 
will additionally follow their Trust incident reporting mechanisms and will document this 
within their TMF/ISFs. 
 
16.2 Adverse Events and Serious Adverse Events Sponsor Reporting Requirements  
Adverse events are any untoward medical occurrence in a patient or study participant, 
which does not necessarily have a causal relationship with any study activities. These do not 
require reporting to the Sponsor, but the severity, causality and expectedness will be 

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recorded in the participant’s medical records, REDCap entry, and AE log, with a description 
of clinical symptoms and the event, including dates as appropriate.  
 
In some instances, unexpected and related SAEs may occur in observational research. All 
reportable SAEs will be recorded in the medical records and CRF, and reported to the 
Sponsor via the JRO REDCAP research incident reporting form or research-
incidents@ucl.ac.uk, within 5 working days of becoming aware of the event. The CI/PI will 
respond to any SAE queries raised by the Sponsor as soon as possible. 
 
16.3 Incidental Findings in Research 
All research staff will follow participating sites’ incidental findings policies, and training on 
this will be provided as part of initiation to the research study. 
 
16.4 Protocol deviations and notification of protocol violations 
Protocol deviations are usually an unintended departure from the expected conduct of the 
study protocol/SOPs, which does not need to be reported to the Sponsor. The CI will 
monitor protocol deviations, and if found to frequently recur, will discuss in the first 
instance with the Sponsor to determine re-classification and reporting requirements. 
 
A protocol violation is a breach which is likely to effect to a significant degree: – 
(a) the safety or physical or mental integrity of the participants of the study; or 
(b) the scientific value of the study 
The CI and Sponsor will be notified immediately of any case where the above definition 
applies via research-incidents@ucl.ac.uk or UCL REDCap incident reporting form. 
 
16.5 NHS Serious Incidents and near misses  
A serious incident or near miss is any unintended or unexpected event that could have or 
did lead to harm, loss or damage that contains one or more of the following components: 
a. It is an accident or other incident which results in injury or ill health. 
b. It is contrary to specified or expected standard of patient care or service. 
c. It places patients, staff members, visitors, contractors or members of the public at 
unnecessary risk. 
d. It puts the Trust in an adverse position with potential loss of reputation. 
e. It puts Trust property or assets in an adverse position or at risk. 
Serious Incidents and near misses will be reported to the Sponsor and Trust Quality & Safety 
department as soon as the study team becomes aware of them. 
 
16.6 Complaints from research participants 
In the first instance, research participant complaints will be reported to the CI/PI to 
investigate, as documented in the patient information sheet(s), and to the Sponsor [via 
research-incidents@ucl.ac.uk, following the UCL Complaints from Research Subjects about 
UCL Sponsored Studies and Trials policy]. For participants who are NHS patients, complaints 
will be reported to the NHS Complaints Manager at the Trust where the recruitment and 
study procedures was undertaken. Complaints from NHS patients are handled under NHS 

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complaints policies and procedures, with involvement from PALS and the Sponsor where 
necessary. 
 
17 MONITORING AND AUDITING 
The CI will ensure there are adequate quality and number of monitoring activities conducted 
by the study team. This will include adherence to the protocol, procedures for consenting 
and ensure adequate data quality. 
 
The CI will inform the Sponsor should he/she have concerns which have arisen from 
monitoring activities, and/or if there are problems with oversight/monitoring procedures. 
 
18 TRAINING 
The Chief Investigator will review and provide assurances of the training and experience of 
all staff working on this study.  Appropriate training records will be maintained in the study 
files. 
 
All staff working on this study will be required to have undertaken GCP training within the 
last two years. Study specific training with regards to the protocol and procedures will be 
undertaken by all staff. 
 
19 INTELLECTUAL PROPERTY 
All background intellectual property rights (including licences) and know-how used in 
connection with the study shall remain the property of the party introducing the same and 
the exercise of such rights for purposes of the study shall not infringe any third party’s 
rights. 
 
All intellectual property rights and know-how in the protocol, the study data and in the 
results arising directly from the study, but excluding all improvements thereto or clinical 
procedures developed or used independently of the study by each participating site, shall 
belong to UCL. All intellectual property rights deriving or arising from the material or any 
derivations of the material provided to UCL by the participating site shall belong to UCL. 
Each participating site agrees that by giving approval to conduct the study at its respective 
site, effectively assigns all such intellectual property rights (“IPR”) to UCL and discloses all 
such know-how to UCL. 
 
Nothing in this section shall be construed so as to prevent or hinder the participating sites 
from using its own know how or clinical data gained during the performance of the study, as 
its own risk, in the furtherance of its normal activities or providing clinical care to the extent 
that such use does not result in the disclosure or misuse of confidential information of the 
infringement of an intellectual property rights of UCL, or their funder. This section does not 

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permit the disclosure of any of the study data, all of which remain confidential until 
publication of the results of the study. 
 
20 INDEMNITY ARRANGEMENTS 
UCL holds insurance against claims from participants for harm caused by their participation 
in this clinical study. Participants may be able to claim compensation if they can prove that 
UCL has been negligent. However, as this clinical study is being carried out in a hospital, the 
hospital continues to have a duty of care to the participants of the clinical study. UCL does 
not accept liability for any breach in the hospital’s duty of care, or any negligence on the 
part of hospital employees. This applies whether the hospital is an NHS Trust or otherwise. 
 
Participants may also be able to claim compensation for injury caused by participation in 
this clinical study without the need to prove negligence on the part of UCL or another party. 
Participants who sustain injury and wish to make a claim for compensation should be 
advised to do so in writing in the first instance to the Chief Investigator, who will pass the 
claim to the Sponsor’s Insurers, via the Sponsor’s office. 
 
Hospitals selected to participate in this clinical study shall provide clinical negligence 
insurance cover for harm caused by their employees and a copy of the relevant insurance 
policy or summary shall be provided to UCL upon request. 
 
21 ARCHIVING 
UCL and each participating site recognise that there is an obligation to archive study-related 
documents at the end of the study (as such end is defined within this protocol). The Chief 
Investigator confirms that they will archive the study master file at UCL for the period 
stipulated in the protocol and in line with all relevant legal and statutory requirements.  
 
The Trial Master File will be archived at UCL, in accordance with the UCL Retentions 
Schedule and Policy. It will be archived for a minimum of 5 years from the study end, and no 
longer than 20 years from study end. 
 
22 PUBLICATION AND DISSEMINATION 
A dissemination plan will be co-produced with the community advisory group (see Section 
10.2 Community Advisory Group) covering academic and community dissemination. The 
strategy will include, but not be limited to: 
• Abstract submission for presentation at national and international conferences, such 
as those organised by BASHH, BHIVA, BIA, and the European Congress of Clinical 
Microbiology and Infectious Diseases (ECCMID). 
• Manuscript submission to key peer-reviewed academic journals.  
• Public and community focused lay summaries of the research, co-written with the 
community advisory group and community collaborator The Love Thank (see Section 

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10 PPI). These will be shared by on online. Lay summaries will be sent to all 
participants. 
• Dissemination event for clinicians, academics, community organisations, public 
health officials, policymakers. Participants will be invited to attend the event, and 
this will be promoted on social media.  
Individual level findings will not be reported back to participants.  
 
The investigators and academic collaborators will be involved in reviewing drafts of 
academic manuscripts, abstracts, press releases and any other publication arising from this 
study. Authorship will be determined in accordance with the ICMJE guidelines and other 
contributors will be acknowledged. All outputs will acknowledge that the research was 
funded by BIA, BHIVA, and NIHR. Community advisory group members will be acknowledged 
in all outputs (anonymously if preferred), and where appropriate included in authorship. 
  
23 REFERENCES 
 
1. Kohli M et al. Sex Transm Infect 2022; 98(3): 235-6. 
2. Kohli M et al. Sex Transm Infect 2022; 98(2): 158 
3. Luetkemeyer AF et al. New Engl J Med 2023; 388(14): 1296-306. 
4. Molina JM et al. Conference on Retroviruses and Opportunistic Infections 2024; Denver, 
USA. Abstract #124 
5. UKHSA. Sexually transmitted infections and screening for chlamydia in England: 2022 
report. 
6. UKHSA. Rise in extremely drug-resistant Shigella in gay and bisexual men. 2022 
7. O'Halloran C et al. Sex Transm Infect 2021; 97(6) 429-433 
8. Park JJ et al. Sex Transm Dis 2021; 48(9): 615-619 
9. Spinelli MA et al. Sex Transm Dis 2019; 46(4): e32-e4. 
10. Kong FYS, Kenyon C, Unemo M. J Antimicrob Chemother 2023. 
11. Unemo M, Kong FYS. Nat Rev Urol 2023; 20(9):522-523 
12. UKHSA. Gonococcal resistance antimicrobials surveillance programme report. GRASP 
report: data to June 2023.  
13. Molina JM et al. Lancet Infect Dis 2018; 18(3): 308-17. 
14. Bolan RK et al. Sex Transm Dis 2015; 42(2): 98-103. 
15. Grennan T HM et al. Conference on Retroviruses and Opportunistic Infections 2021; 
2021. Abstract #709 
16. Traeger ME et al. Clin Infect Dis 2023 [online ahead of print] 
17. Stewart J et al. N Engl K Med 2024; 389(24):2331-2340 
18. Chow EPF, Fairley CK. Lancet HIV 2019; 6(9): e568-e9. 
19. Mitchell HD et al. J Infect 2023; 86(1): 33-40. 
20. Vujkovic-Cvijin I, Somsouk M. Current HIV/AIDS Rep 2019; 16(3): 204-13. 
21.  Kenyon C, Osbak K. Med Hypotheses 2014; 83(2): 196-202. 
22. Li S et al. Front Cell Infect Microbiol 2021; 11: 695515. 
23. Vijay A, Valdes AM. Eur J of Clin Nutr 2022; 76(4): 489-501. 
24. Kong FYS, Kenyon C, Unemo M. J Antimicrob Chemother 2023. 
25. Van Dijck C et al. J Infect 2023; 86(4): 329-37. 

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26. Ho J et al. Gut Microbes 2020; 12(1): 1700755. 
27. Tuddenham S et al. Dig Dis Sci 2020; 65(3): 800-17. 
28. UCL Data Safe Haven. https://www.ucl.ac.uk/isd/services/file-storage-sharing/data-safe-
haven-dsh  
 
24 APPENDICES 
Include here a list of the supplementary information and documents that will support the 
protocol and information contained therein, e.g. PIS, ICF, schedule visit, assessment tools, 
delegation log, case report forms, questionnaires, scales, tables, charts, diagrams, 
manufacturer’s brochures. 
 
It is not advisable to insert copies of documents such as the PIS and ICF due to version 
control and document management issues. You may wish to list the document titles here or 
delete if unnecessary. 
 
24.1 Associated Documents 
Include here supplementary information and documents that will support the protocol and 
information contained therein. 
E.g. data dictionary 
 
Document Name 
Document Version 
Document Date