Pilot Implementation of HIV Self-testing Delivery in Private Pharmacies Combined to a Respondent Driven Sampling Method to Improve HIV Testing for MSM and TGW in Phnom Penh - ANRS 0100s
Conditions: HIV Infections
Sponsor: ANRS, Emerging Infectious Diseases

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 1/52 
 Pilot implementation of HIV self-testing delivery in 
private pharmacies combined to a Respondent Driven 
Sampling method to improve HIV testing for MSM and 
TGW in Phnom Penh – ANRS 0100s 
 
 
Protocol version 1.1 – Date: 18th April 2022 
 
 
 
Ethics committee approvals 
Cambodia:   
Name of the committee:  National Ethic Committee for Health Research (NECHR) 
 
 
Date of approval:   
 
Sponsor: 
 
Institut national de la santé et de la recherche médicale-ANRS Maladies Infectieuses Emergentes (Inserm - 
ANRS) 
2 rue Oradour-sur-Glane – 75015 Paris, France Tél. : 01 53 94 60 00 - Fax : 01 53 94 60 01 
 
Coordinating investigators: 
 
Cambodian coordinator  
French coordinator  
Pr. SAPHONN Vonthanak  
Pr. Bruno SPIRE 
 
MONITORING AND DATA MANAGEMENT CENTER (MDMC): 
 
Prof. Mam Sovatha 
University of Health Sciences 
73 blvd Monivong, Sras Chak, Daun Penh, Phnom Penh Cambodia Phnom Penh, Cambodia  
 
 
 
 
 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 2/52 
 
PAGE DE SIGNATURES 
Pilot implementation of HIV self-testing delivery in private 
pharmacies combined to a Respondent Driven Sampling method to 
improve HIV testing for MSM and TGW in Phnom Penh   
Protocol version 1.1 – Date 18th April 2022 
Clinicaltrial.gov registration number N/A 
Ethics committee approvals 
Cambodia:   
Name of the committee:  National Ethic Committee for Health Research (NECHR) 
 
 
Date of approval:   
 
Sponsor signature 
 
Inserm-ANRS Maladies infectieuses Emergentes  
Director: Prof. Yazdan Yazdanpanah 
2 rue Oradour-sur-Glane  
 75015 Paris, France Tel:   +33 153 94 60 46 / 60 00 
Fax : +33 153 94 60 01 
Paris, Date :  
Name :  
Signature 
Coordinating investigators signature 
Pr SAPHONN Vonthanak 
University of Health Sciences (UHS) 
73 Preah Monivong Bvd 
Phnom Penh, Cambodia 
Email: vonthanak@uhs.edu.kh  
 
Date:  
Name : Pr SAPHONN Vonthanak 
Signature 
Pr Bruno SPIRE 
Sciences économiques et sociales de la santé et traitement de 
l'information médicale (SESSTIM) 
Faculté de Médecine 27 Bd Jean Moulin 13385 Marseille Cedex 5, 
France 
Email: bruno.spire@inserm.fr 
Date : April, 8th, 2022 
Name : Pr Bruno SPIRE 
Signature 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 3/52 
Table of Contents 
STUDY PROTOCOL VERSIONS 1.1 ..................................................................................................... 5 
1. 
STUDY TEAM MEMBERS ............................................................................................................. 7 
1 
STUDY SUMMARY ......................................................................................................................... 9 
2 
STUDY SYNOPSIS......................................................................................................................... 12 
3 
SCIENTIFIC RATIONALE ........................................................................................................... 12 
Study main hypothesis .....................................................................................................................................14 
4 
OBJECTIVES OF THE STUDY ................................................................................................... 15 
5 
METHODOLOGY .......................................................................................................................... 15 
Study design ......................................................................................................................................................15 
Study overview ..................................................................................................................................................15 
Tentative study agenda ....................................................................................................................................16 
6 
STUDY POPULATION .................................................................................................................. 16 
7 
STUDY ENDPOINTS..................................................................................................................... 17 
Primary endpoint ..............................................................................................................................................17 
Secondary endpoints ........................................................................................................................................17 
8 
STRATEGIES AND TREATMENTS ............................................................................................ 17 
Strategies and Treatments used in the study .................................................................................................17 
9 
STUDY IMPLEMENTATION ....................................................................................................... 18 
Patients participation in the study ..................................................................................................................18 
Information .......................................................................................................................................................18 
Consent ..............................................................................................................................................................18 
Withdrawal of consent and loss to follow-up .................................................................................................20 
Consent withdrawal ..........................................................................................................................................20 
Loss to follow-up ...............................................................................................................................................21 
10 LABORATORY EVALUATIONS .................................................................................................. 21 
Samples collection and tests .............................................................................................................................21 
Biobank ..............................................................................................................................................................21 
11 ADVERSE EVENTS AND IN UTERO EXPOSURE ................................................................... 21 
12 SCIENTIFiC BOARDS AND COMMITTEES ............................................................................. 21 
a) 
Scientific Advisory Board (SAB) .........................................................................................................21 
13 COORDINATION, MONITORING, DATA MANAGEMENT .................................................... 22 
Data management .............................................................................................................................................23 
Data collection ...................................................................................................................................................24 
Data entry and checking ..................................................................................................................................24 
Data storage ......................................................................................................................................................24 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 4/52 
Data protection .................................................................................................................................................24 
Data Tracking ...................................................................................................................................................25 
Data Export .......................................................................................................................................................25 
Data Security .....................................................................................................................................................25 
Monitoring.........................................................................................................................................................26 
14 STATISTICAL ANALYSEs ........................................................................................................... 26 
Calculation of number of participants needed ...............................................................................................26 
Analysis plan .....................................................................................................................................................27 
15 SCIENTIFIC COMMUNICATION .............................................................................................. 28 
16 Ethics and legal considerations ...................................................................................................... 28 
17 ACCESS TO DATA AND SPECIMENS ....................................................................................... 30 
18 DUTIES OF INVESTIGATORS ................................................................................................... 31 
19 REFERENCES ............................................................................................................................... 31 
20 ANNEXES ....................................................................................................................................... 34 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 5/52 
STUDY PROTOCOL VERSIONS 1.1 
 
 Version # 
Date 
 Amendment 
# 
Main modifications 
1.0 
15/03/2021 
N/A 
Initial protocol (submitted for grant approval) 
1.1 
18/04/2022 
1 
-Two main modifications have been made into the initial 
protocol version 1.0: external website (in place of 
smartphone application) and salivary HIV self-test (in 
place of fingerstick whole blood, venipuncture whole 
blood or serum/plasma). 
 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 6/52 
LIST OF ABBREVIATIONS 
 
AIDS 
Acquired immunodeficiency syndrome  
ANRS|MIE 
ANRS Maladie Infectieuses Emergentes 
ART  
Antiretroviral therapy 
CBO 
Community-based organisation 
CEPED 
Centre Population et Développement 
CNIL 
Commission nationale de l'informatique et des libertés 
CRA 
Clinical Research Assistant 
e-CRF 
Electronic case report form 
DSMB 
Data safety & monitoring board 
FG 
Focus Groups 
GCP 
Good clinical practice 
GMO 
Grant Management Office  
HIV   
Human immunodeficiency virus  
HIVST 
HIV Self-Test  
MSM 
Men who have sex with men  
NCHADS  
National Center for HIV/AIDS, Dermatology and STD 
NECHR 
National Ethics Committee for Health Research 
RDS 
Respondent-driven sampling 
SAB 
Scientific Advisory Board  
SOPs    
Standardized operating procedures 
TGW 
Transgender women  
TMF 
Trial Master File 
TWG 
Technical Working Group 
WHO  
World health organization 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 7/52 
1. STUDY TEAM MEMBERS 
 
SPONSOR 
Inserm / ANRS | MIE 
2 rue Oradour-sur-Glane – 75015 Paris, France.  
Phone: +33 1 53 94 60 00 
 
COORDINATING INVESTIGATORS 
Pr SAPHONN Vonthanak 
University of Health Sciences (UHS) 
73 Preah Monivong Bvd 
Phnom Penh, Cambodia  
Email: vonthanak@uhs.edu.kh  
 
Pr Bruno SPIRE 
Sciences économiques et sociales de la santé 
et traitement de l'information médicale 
(SESSTIM)  
Faculté de Médecine 27 Bd Jean Moulin 
13385 Marseille Cedex 5, France 
Email: bruno.spire@inserm.fr 
STUDY COORDINATOR  
Dr. DARY Chhavarath  
University of Health Sciences 
Phone : +85517676953 
Email : dr_chhavarath@uhs.edu.kh 
 
 
CO-INVESTIGATOR AND CLINICAL 
COORDINATOR 
 
 
Dr. Emilie Mosnier   
University of Health Sciences 
Phone : +85512479313 
Email : oliseg@hotmail.com 
 
MONITORING AND DATA MANAGEMENT CENTER  
Monitoring / statistical analysis  
Methodology/Biostatistics 
 
 
Dr. DARY Chhavarath  
Public Healht Unit, University of Health 
Sciences, Phnom Penh, Cambodia, 73 Preah 
Monivong Blvd, Phnom Penh, Cambodia  
System development and data managing: 
 
Mr. MAN Manith 
Head of IT Department, University of Health 
Sciences, Cambodia, 73 Preah Monivong Bvd 
Phnom Penh, Cambodia 
Mr. Un Vireak,  
Deput Head of IT Department, University of 
Health 
Sciences, 
Cambodia, 
73 
Preah 
Monivong Bvd 
Phnom Penh, Cambodia 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 8/52 
COLLABORATIVE RESEARCH TEAMS 
Dr. OUK Vichea 
National Center for HIV/AIDS, Dermatology and 
STD (NCHADS) 
#245H, Sreet 6A, Phum Kean Khlang,12100 
Phnom Penh, Cambodia.  
 
Dr. Joseph LAMARANGE 
Institut de Recherche pour le 
Développement - UMR 196 IRD 
Centre Population et Développement 
(Ceped, UMR 196, Université Paris Cité, IRD, 
Inserm) 
45 rue des Saints Pères 75006 Paris 
FRANCE 
 
PARTNERS 
U-Care Pharmacy  
29 Mao Tse Toung Blvd (245), Phnom Penh 
12302, Cambodia.  
 
 
Chhouk Sor Clinic 
Oknha Kleang Moeung St. (70), Phnom 
Penh, Cambodia. 
 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 9/52 
  
1 STUDY SUMMARY 
Clinicaltrial Id: 
 
Title of Study: Pilot implementation of HIV self-testing delivery in private pharmacies combined 
to a Respondent Driven Sampling method to improve HIV testing for MSM and TGW in Phnom 
Penh 
Short title – Sponsor N°: -ANRS 0100s 
 
Sponsor: Institut national de la santé et de la recherche médicale - ANRS Emerging Infectious 
diseases (Inserm-ANRS| MIE) 
 
Coordinating Investigator(s):  
Pr. SAPHONN Vonthanak, University of Health Sciences, Cambodia 
Pr. Bruno SPIRE, SESSTIM, France 
 
Participating countries: CAMBODIA AND FRANCE 
_______________________________________________________________________________________________________________ 
Primary objective:  
Evaluate the feasibility of HIV self-testing (HIVST) delivery by a private pharmacy network among 
men who have sex with men (MSM) and transgender women (TGW) recruited through a classic 
and digital Respondent Driven Sampling method to improve HIV testing in Phnom Penh, 
Cambodia 
Secondary objectives: 
• 
Evaluate the acceptability and appropriateness of the strategy 
• 
Identify barriers and facilitators 
• 
Estimate the linkage to confirmatory testing for those with a reactive test and linkage to 
HIV care and ART for those with a positive confirmatory HIV test  
• 
Estimate linkage to pre-exposure prophylaxis (PrEP) services for negative participants  
• 
Estimate the characteristics of participants and compare to those reported in Integrated 
Biological and Behavioral Survey (IBBS 2019) for MSM and TGW in Cambodia 
• 
Evaluate the adherence of participants to a 6-monthly repeated HIV testing 
 
Methodology:  
 
An interventional pilot study using a mixed qualitative and quantitative approach will be carried 
out in order to evaluate the feasibility, acceptability and appropriateness of the strategy and to 
identify barriers and facilitators. 
 
The participant recruitment method will be designed as a Respondent Driven Sampling (RDS) by 
recruiting initial seeds both at hotspots and on social networks. Prior to seed recruitment, a 
consultative meeting will be conducted in order to optimise the selection criteria of the seeds. The 
seeds will then distribute electronic and paper coupons to their networks physically and via social 
media, messaging and calling applications such as Twitter, Whatapp and Telegram (e-coupons). 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 10/52 
Each recruited participant will bring the coupon to be scanned at partner pharmacies to receive 
direct and free access to one HIVST kit. Partner pharmacies with a proper dedicated room/space 
securing privacy and secrecy in Phnom Penh are the study sites. There, trained community 
workers who get notified by partner at each visit of participant will do the study visit including 
information/consent (annexe 1 and 2), e-CRF filling (annexe 3) and give a link of an external 
website to send the HIV test results and receive information or advices. These recruited 
individuals will be considered as wave 1 of recruitment and will each receive 10 additional 
coupons to recruit the members of their networks. The next round of individuals recruited and 
enrolled will be considered as wave 2, and so on. 
 
After 6 months, a qualitative assessment via focus groups will be conducted among MSM, TGW 
and pharmacists to evaluate feasibility, acceptability and appropriateness of the intervention and 
to identify barriers and facilitators.  
 
Several ART sites/HIV clinics particularly in charge of key populations will be specifically selected 
as participating centers in order to collect information on linkage to care or prevention services 
for positive and negative participants, respectively. 
 
Each participant will be followed during 18 months and encouraged to perform a 6-monthly HIV 
testing during this period. 
 
 
Expected enrolment  
 
 
A pragmatic approach is carried out in which the enrolment will be stopped at the end of the 
inclusion period or if the number of participants reaches a maximum of 1500. 
 
Outcomes 
 
With regard to the novel intervention, the outcomes will focus on its feasibility, adoption, 
acceptability and appropriateness.  
 
The primary outcomes will be the HIV self-testing uptake defined as the number of HIV self-tests 
delivered / total number of coupons distributed 
 
The secondary outcomes will be:  
• 
Proportion of HIVST result’s recorded / total number of HIVST delivered 
• 
Proportion of paper and electronic coupons delivered and recorded 
• 
Number of HIV tests realized / number of HIV tests results non recorded   
• 
Proportion of MSM/TGW with positive HIV self-tests linked to an ART site   
• 
Proportion of negative MSM/TGW linked to PrEP services  
• 
Characteristics of participants recruited (sociodemographic, sexual behavior, utilization 
of dating application, substance use) in comparison with IBBS 2019 report 
• 
Proportion of participants with 6-monthly repeated HIV testing during 18 months  
   
Outcomes of acceptability and appropriateness will be explored during focus groups: comfort, 
usefulness, suitability, confidentiality, credibility, advantages and barriers.   

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 11/52 
 
  
Eligibility 
 
 
Inclusion criteria 
• 
To be aged from 18 years old (legal age in Cambodia) 
• 
For MSM, to have at least one oral or anal intercourse with another man in the past 12 
months 
• 
For TGW, to be biologically a male at birth and self-identified as a woman or third gender 
and have at least one oral, anal or vaginal intercourse with another man in the past 12 
months 
 
Non-inclusion criteria 
• 
Known HIV positive status 
 
Statistical methods 
 
We want to evaluate the feasibility of the intervention to improve HIV testing among MSM and 
TGW in Phnom Penh. We will use a pragmatic approach with the objective to recruit the maximum 
of MSM and TGW. According to the IBBS 2019, the estimated number of MSM in Phnom Penh is 
6300 and the estimated number of TGW is 1400. 
With 1500 participants (1000 MSM and 500 TGW), we will be able to estimate an HIV self-test 
uptake of 70% to within a 95% confidence interval of +/- 2 – 2.5% (width of the confidence 
interval (in %) = 1.96 x √( p x (1-p) / n)). 
 
Estimated planning or study timetable  
 
• 
Protocol submission: December 2022 
• 
Study implementation: February 2023 – July 2023  
• 
Data collection: August 2023 – April 2025 (18 months) 
• 
Duration of the study: 24 months  
 
 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 12/52 
2 STUDY SYNOPSIS  
 
 
Figure 1: study flow and recruitment process by respondent-driven sampling  
 
3 SCIENTIFIC RATIONALE  
The sharp rise in the number of new HIV infections among MSM in Asia has continued, and sexual 
activity between men remains stigmatized and often hidden. HIV prevalence among MSM was 5% 
or higher in 10 of the 24 countries that reported these data to UNAIDS in 2019 (1). About 30% of 
all new infections in Asia are in MSM. In the region, HIV incidence is high among young (15-24 
years old) MSM; a recent publication reported an HIV incidence of 7.4 per 100 person-years in 
Bangkok in this population (2).  
 
Similar to MSM’s HIV infection, in Asia and the Pacific, it is widely reported that most new HIV 
infections will be among men who have sex with men and transgender people by the year 2020. 
Limited studies have been reported regarding HIV surveillance, HIV and STI prevalence, 
population size estimations, or behavior patterns for either transgender women or transgender 
men in the region. The most current data documenting HIV infection rates amongst transgender 
people only include transgender women in urban settings. Nevertheless, the data shows 
disturbing HIV infection rates throughout the region: Delhi 49%, Mumbai 42%, Phnom Penh 37%, 
Jakarta 34%, Surabaya 25%, Bandung 14%, Chaing Mai 18%, Phuket 12%, Bangkok 11%, Lahore 
0.5% (3).  
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 13/52 
Late diagnosis is a serious barrier to tackling HIV. Around 69% of people living with HIV in the 
Asia and the Pacific region were aware of their status in 2018, up from 58% in 2015. However, 
this means around 1.9 million people did not know they were HIV positive.  
 
Progress on testing varies greatly between countries. In Thailand, 94% of people living with HIV 
were aware of their status in 2018, as were 86% of people living with HIV in Malaysia and 82% in 
Cambodia. At the other end of the spectrum, only 37% of people living with HIV in Bangladesh 
and 14% of people in Pakistan were aware of their status.  
 
Stigma, discrimination and punitive legal environments prevent many people from key 
populations from accessing testing services (4). Indeed in Malaysia and Sri Lanka, the HIV testing 
and awarness among MSM account for 43.3% and 40.3%, respectively while the HIV testing and 
awarness for TG people are 43% and 36.9%, respectively (5).   
 
Despite Cambodia’s admirable achievements the 90-90-90 targets by 2020, the HIV epidemic 
among key populations and, as yet, unidentified priority populations is an abiding concern. The 
latest available key-population data show HIV prevalence is 2.3% among men who have sex with 
men (MSM) and 5.9% among transgender women (TGW) (6,7). Despite this high prevalence rate, 
remain low the uptake of HIV testing among men who have sex with men (MSM<50%) and 
transgender women (TGW=39%) and consistent condom use (69% in MSM during anal sex and 
38% for TGW with non-commercial sexual partners) (8). The IBBS 2019 report highlighted that 
about half of MSM and one third of TGW did not report any HIV testing or since more than 12 
months. This suggests that undiagnosed HIV infection may persist in hard-to-reach MSM and TGW 
and new modality of HIV-testing approaches are hence needed to improve the uptake of HIV 
testing among these key populations. In addition, of those who reported HIV testing, the majority 
of MSM and TGW were tested at Community-based organizations (CBO) facilities (23.5% for MSM 
and 36.2% for TGW) and by CBO outreach workers (53.4% for MSM and 53.8% for TGW) while 
private facilities are poorly used for HIV (9).  
 
From the perspectives of some users not only among general population but also “hidden” or 
“marginalized populations” such as MSM and TGW, results of HIV self-tests should be interpreted 
in private settings in order to guarantee complete anonymity. HIVST is a process in which an 
individual performs an HIV rapid diagnostic test (RDT) and interprets the result in private. Lay 
users can perform HIVST reliably and accurately and achieve performance comparable to that of 
trained health-care workers (10). HIV self-testing has the potential to increase the number of 
people living with HIV who have access to testing, know their status, are diagnosed and initiate 
treatment. HIV self-testing shares many characteristics with current HIV testing and counselling 
approaches, including products, accuracy issues, linkage to care, potential benefits and risks and 
regulatory policies and frameworks (11). Of some key populations, HIV self-testing increased 
testing frequency among high-risk MSM and could increase HIV diagnose in the trans community 
(12,13).  In 2016, WHO recommended HIV self-testing (HIVST) as a safe, accurate and effective 
way to reach people who may not test otherwise, including people from key populations, men and 
young people (10). Representatives from 13 countries across Asia and the Pacific gathered to 
develop road maps to implement and expand pre-exposure prophylaxis (PrEP) and HIV self-
testing in the region (14).  
 
In 2017, Cambodia developed national consolidated guidelines on HIV testing services in which 
many approaches including HIV self-testing (HIVST) are recommended to increase the HIV test 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 14/52 
uptake, especially among hard-to-reach and key populations (15). Recent evaluation of the B-
IACM in Cambodia revealed that 66.5% who received assisted HIVST want to confirm their HIV 
status (16). Even though MSM and TGW had not heard about HIVST, all of them expressed 
willingness to try it (17).  
 
While HIVST kits are distributed primarily from public health facilities, the HIVST is also available 
through private ways and channels. Some studies including the one conducted in Cambodia by Pal 
et al. (2016) suggested that men who have sex with men, transgender women wish or prefer 
HIVST to be available over-the-counter at pharmacies and other locations or through the Internet 
(17,18). HIVST is already formally and informally available, and it will likely become increasingly 
available. Indeed, HIVST kits are authorised to be dispensed from pharmacies in some countries 
such as USA and France (19,20). In addition, HIVST were reported informally on sale through the 
Internet and in pharmacies in many countries – with specific reports on this from Australia, China, 
Namibia, Peru, South Africa, Philippines and Malaysia (21).  
 
Respondent driven sampling (RDS), a form of peer referral-based sampling, has become a popular 
strategy to recruit “hidden” or “marginalized populations” such as MSM and TGW. RDS 
implementation resembles snowball sampling with several critical caveats. Initial participants are 
purposefully recruited to be “seeds” as long as they fit the study’s eligibility criteria. After 
completing the study procedures, seeds are offered a limited number of vouchers to recruit their 
peers to participate. When vouchers are redeemed, eligible participants also complete the same 
study procedures and are asked to recruit their peers, and this continues until recruitment goals 
are met. Using specially formulated statistical programs, sampling weights are developed and 
applied to estimate population parameters. For the purpose of RDS, effective seeds generate large 
recruitment chains and samples, which has been shown to be associated with motivation and a 
commitment to the research goals (22). 
 
To mitigate some of the challenges of implementing the methodology, notably slow recruitment 
rates, innovation around conventional RDS can be helpful (23). Indeed, since there has been rise 
of using the Internet and online communities of gay and bisexual men in a few decades to facilitate 
new connections for the purpose of information seeking, socializing and seeking sex, several 
studies have reported innovative internet- and application-based RDS strategies in different 
aspects of AIDS/HIV research such as improving uptake of HIV self-testing among MSM, providing 
technical support, counselling and referrals for further HIV testing services, HIV prevention, care 
and treatment and other services (24–28). 
Study main hypothesis 
• 
The main hypothesis is that private pharmacies could be able to deliver HIV self-testing 
kits giving the advantage of confidentiality, anonymity and time-saving, which could be an 
effective intervention to improve HIV testing coverage for MSM/TGW. 
• 
The second hypothesis is that a RDS method with a diversity of seeds recruited at hotspots 
and on social networks could help to identify a new network of hidden key population. 
 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 15/52 
4 OBJECTIVES OF THE STUDY 
Primary objective:  
 
• 
Evaluate the feasibility of HIV self-testing (HIVST) delivery by a private pharmacy 
network among men who have sex with men (MSM) and transgender women (TGW) 
recruited through a classic and digital Respondent Driven Sampling method to improve 
HIV testing in Phnom Penh, Cambodia 
Secondary objectives: 
• 
Evaluate the acceptability and appropriateness of the strategy 
• 
Identify barriers and facilitators 
• 
Estimate the linkage to confirmatory testing for those with a reactive test and linkage to 
HIV care and ART for those with a positive confirmatory HIV test  
• 
Estimate linkage to pre-exposure prophylaxis (PrEP) services for negative participants  
• 
Estimate the characteristics of participants and compare to those reported in Integrated 
Biological and Behavioral Survey (IBBS 2019) for MSM and TGW in Cambodia 
• 
Evaluate the adherence of participants to a 6-monthly repeated HIV testing 
5 METHODOLOGY 
Study design 
An interventional pilot study using a mixed qualitative and quantitative approach will be carried 
out in order to evaluate the feasibility, acceptability and appropriateness of the strategy and to 
identify barriers and facilitators. 
 
The participant recruitment method will be designed as a Respondent Driven Sampling (RDS) by 
recruiting initial seeds both at hotspots and on social networks.  
 
After 6 months, a qualitative assessment by focus groups discussion (FGD) will be conducted 
among MSM, TGW and pharmacists to evaluate feasibility, acceptability and appropriateness of 
the intervention and to identify barriers and facilitators.  
 
Each participant will be followed during 18 months and encouraged to perform a 6-monthly HIV 
testing during this period. 
Study overview  
The intervention will be designed as a RDS by recruiting initial seeds both at hotspots and on 
social networks. 15 initial seeds will be recruited. Seeds will come to the study site for checking 
inclusion criteria and receiving information on self-testing, benefits of their participation and 
recruiting other participants in their networks along with the important details about the study. 
Once consent to the study, the seed is provided with two types of coupons for HIVST kit at partner 
pharmacy: 5 electronic coupons (e-coupons) consisting of a pictured unique anonymous QR code 
and identifier and address of partner pharmacies; 5 paper coupons consisting of a printed unique 
anonymous QR code, identifier and address of partner pharmacies. The seeds will then distribute 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 16/52 
electronic and paper coupons to their networks physically and via social media, messaging and 
calling applications such as Twitter, Whatapp and Telegram (e-coupons).  
 
Each recruited participant will bring the coupon to be scanned at partner pharmacies to receive 
direct and free access to one HIVST kit. Partner pharmacies with a proper dedicated room/space 
securing privacy and secrecy in Phnom Penh are the study sites. There, trained community 
worker/research team who get notified by partner at each visit of participant will do the study 
visit including information/consent, e-CRF filling and give a link of an external website to send 
the HIV test results and receive information or advices.  
 
These recruited individuals will be considered as wave 1 of recruitment and will each receive 10 
additional coupons to recruit the members of their networks. The next round of individuals 
recruited and enrolled will be considered as wave 2, and so on. The number of 10 coupons was 
selected to avoid a bias risk related to participation incentives.   
 
To facilitate the return of HIVST kit results, participant will upload the picture of results labeled 
with their identifier directly using the link of the external website that they received from 
community worker/research team during their visits at pharmacy. In case of any question, they 
could reach community worker/research team by hotline number. According to the results, the 
participants will be proposed with a support for linkage to confirmatory test or to PrEP services. 
Each non-reactive participant will be provided another new coupon (paper or electronic format 
upon their preference) with a reminder to perform a 6-monthly HIV testing during 18 months. 
They will not be granted any token or incentives if they fail to return the result of HIVST kit taken 
at pharmacies. These incentives are also added upon the number of recruited members of their 
networks using common money transfer and payment services in Cambodia such as Wing, 
TrueMoney.  
 
After 6 months, a qualitative assessment will be conducted to evaluate feasibility, acceptability 
and appropriateness of the intervention and to identify barriers and facilitators.  
 
Several ART sites/HIV clinics particularly in charge of key populations will be specifically selected 
as participating centers in order to collect information on linkage to care or prevention services 
for positive and negative participants, respectively. 
 
Tentative study agenda  
• 
Protocol submission: December 2022 
• 
Study implementation: February 2023 – July 2023  
• 
Data collection: August 2023 – April 2025 (18 months) 
• 
Duration of the study: 24 months  
6 STUDY POPULATION 
MSM and TGW who are residing in Phnom Penh at the time of enrollment and meet the eligible 
criteria below are the study population: 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 17/52 
• 
To be aged from 18 years old (legal age in Cambodia) 
• 
For MSM, to have at least one oral or anal intercourse with another man in the past 12 
months 
• 
For TGW, to be biologically a male at birth and self-identified as a woman or third gender 
and have at least one oral, anal or vaginal intercourse with another man in the past 12 
months 
7 STUDY ENDPOINTS  
Primary endpoint  
• 
HIV self-testing uptake defined as the number of HIV self-tests delivered / total number 
of coupons distributed 
Secondary endpoints 
• 
Proportion of HIVST result’s recorded / total number of HIVST delivered 
• 
Proportion of paper and electronic coupons delivered  
• 
Number of HIV tests realized / number of HIV tests results non recorded   
• 
Proportion of MSM/TGW with positive HIV self-tests linked to an ART site   
• 
Proportion of negative MSM/TGW linked to PrEP services  
• 
Characteristics of participants recruited (sociodemographic, sexual behavior, utilization 
of dating application, substance use) in comparison with IBBS 2019 report 
• 
Proportion of participants with 6-monthly repeated HIV testing during 18 months  
   
Outcomes of acceptability and appropriateness will be explored during focus groups: comfort, 
usefulness, suitability, confidentiality, credibility, advantages and barriers.   
 
8 STRATEGIES AND TREATMENTS 
Strategies and Treatments used in the study 
The study does not involve with any direct medical treatment. However, intervention after 
delivering HIV test results will be proposed as follow: 
− 
In case of reactive HIV test, the participant could join immediately one research team by 
hotline and messages on the website that will provide support and orientation. After 1 
week, contact with the participant will be done by phone by the research team to confirm 
the linkage to one of the partner ART sites. The linkage between participants and HIV 
clinics will be done by the initial QR code.  
 
If the linkage to confirmatory testing and/or care is not confirmed, we will propose to participant 
additional help of a community worker.     
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 18/52 
− 
In case of non-reactive test, the participant could download in the external website one 
electronic coupon (QR code) to repeat the HIV test every 6 month. Participants will be 
informed on the external website about the possibilities to join the pilot PrEP program in 
Chhouk Sar clinic in Phnom Penh. 
9 STUDY IMPLEMENTATION 
Patients participation in the study 
Information  
Patient participation in this study is voluntary. Each potential participant will be informed 
individually by research team of the purpose, scope of the study, procedures involved, duration of 
follow-up, potential risks and benefits and any discomfort it may entail. In addition to oral 
explanations, a written information sheet will be systematically provided in Cambodian language 
(see Appendix A).  
Consent 
If the patient accepts to be enrolled in the study, s/he will sign the paper and electronic 
consent forms including different consents: global participation, receiving funds, being 
recontacted by phone, participation in FGD. Informed consent must be obtained before any exam 
related to the study. Participants may be given, if they wish, a copy of the paper consent form after 
they sign. 
Intervention  
 
RDS intervention 
 
The seeds will be recruited at hotspots, online applications and social media networks. Hotspots 
include steam sauna and spa and gay bars and clubs. Online applications and social media include 
Facebook groups, twitter, telegram, whatapps and other date applications such as Grindr, Planet 
Romeo, Hornet, Blued.  
 
Prior to seed recruitment, a consultative meeting will be conducted among pimps (a person who 
controls sex workers, especially by finding customers for them, and takes some of the money that 
they earn), procurers (a person who finds sex workers for people who want to have sex with 
them), high class MSM & TGW, network organizers, social media group organizers in order to 
optimize the selection criteria of the seeds. 
 
Selection criteria obtained from the meeting with pimps, procurers, high class MSM, network 
organizers, twitter groups organizer is applied to select the initial seeds that are very likely to lead 
us to reach a large diversity of MSM&TGW population. 
 
A number of 15 seeds will be selected firstly to ensure the representation of gender, age group, 
sexual behaviors, and participation in sex work. If necessary, new seeds could be recruited later. 
Seeds will come to the study site for checking inclusion criteria and receiving information on self-
testing, benefits of their participation and recruiting other participants in their networks along 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 19/52 
with the important details about the study. Once consent to the study, the seed is provided with 
two types of coupons for HIVST kit at partner pharmacy: 1- 5 electronic coupons (e-coupons) 
consisting of a pictured unique anonymous QR code and identifier and address of partner 
pharmacies 2- 5 paper coupons consisting of a printed unique anonymous QR code, identifier and 
address of partner pharmacies. The seeds will provide paper- and e-coupons to their networks 
physically and via social media, messaging and calling applications such as Twitter, Whatapp and 
Telegram (e-coupons). For online application and social media, a peer could be reached by chat 
or call.  
 
When the participant arrives in a partner pharmacy, the coupon (unique QR code with identifier) 
will be scanned by the pharmacist prior to the free delivery of HIV self-test. Community workers 
(CWs) will be then alerted by the pharmacist for study visits to participant directly at the 
dedicated space at the pharmacy. During the visit with CW, participant will :  
− 
Receive the information about the study  
− 
Receive an ID 
− 
Check for eligibility criteria  
− 
Be requested for his/her consent to participate in the study and to different specific 
consents as receiving funds, being recontacted by phone and participation in FGD 
− 
Fill in the detailed e-CRF for sociodemographic status, sexual behaviors, utilization of 
dating application, substance use, knowledge about PrEP and willingness to pay for HIV 
self-testing by using Tablet with the eventual assistance from a community worker 
− 
Receive the information on HIV self-testing instructions, list of partner pharmacies, 
helpline phone number, location of the 2 partners ART sites, location of the HIV clinics 
with prevention services and PrEP delivery availability 
− 
Be provided one free HIV self-testing kit delivered  
− 
Receive the link of the external website to performance HIV test, interpret and send the 
HIV test result, receive necessary information and in case of non-reactive, to receive 
another coupon for 6-monthly test during 18 months 
− 
Receive 10 (paper or electronic) coupons to distribute to peers 
− 
Be asked if the participant would agree to be recontacted for an eventual participation in 
a focus group 
Incentives will be provided in two steps for participants to encourage them to return the results 
of HIVST and recruit their peers. In step one, each participant will receive 2 USD for returning the 
HIVST result successfully to the provided link. In step two, an amount of 1 USD will be provided 
for each recruited peer. This amount was decided as a balance between feasibility 
(encouragement) and sustainability of the strategy (not too high for possible scaling-up).  
 
In case of any issue for tablet use or HIVST kit use, helpline phone number will be available. One 
dedicated community worker funded by the study will be in charge to manage helpline service.  
 
Intervention after delivering HIV test result  
 
In case of reactive HIV test, the participant could join immediately one research team by hotline 
or messages on the website that will provide support and orientation. After 1 week, contact with 
the participant will be done by phone by the research team (if the participant gave consent) to 
confirm the linkage to one of the partner ART sites. The linkage between participants and HIV 
clinics will be done by the initial QR code.  

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 20/52 
If the linkage to confirmatory testing and/or care is not confirmed, we will propose to participant 
additional help of a community worker.     
 
In case of non-reactive test, the participant could download in the external website one electronic 
coupon (QR code) to repeat the HIV test 6 month later. Participants will be informed on the 
external website about the possibilities to join the pilot PrEP program in Chhouk Sar clinic in 
Phnom Penh.  
 
Qualitative assessment  
 
After 6 months, a qualitative assessment will be conducted to evaluate acceptability and 
appropriateness of the intervention. Qualitative assessment will be done by focus groups. Focus 
groups will be conducted in 3 specific populations: MSM, TGW and pharmacists. For each 
population of MSM and TGW, a qualitative sample will be selected in order to capture different 
profiles according to sex behaviors and demographic and socioeconomic characteristics.  
 
Participation to focus groups will be anonymous and voluntary. Participants will be recruited via 
the interview in the pharmacy and by the external website. Focus groups will be conducted in a 
dedicated room, facilitated by a researcher in social and human sciences with the help of the 
project manager, trained to focus groups and using grids describing topics. Each focus group will 
be composed of 9-10 members for a 60-90 minutes discussion that will be recorded to facilitate 
retranscription and translation. Records will be deleted at the end of the study.   
 
The topics included in grids for focus groups with MSM and TGW will be:  
− 
Acceptability of the HIV test delivery: confidence and confidentiality, non-judgmental 
attitude, quality of explanations, location of pharmacies   
− 
Acceptability of the HIV self-testing realization: quality of information and use-
instructions, painful or stress experience, solitude feeling, orientation after testing 
− 
Appropriateness of the strategy: usefulness, perception and improvement of the strategy, 
willingness to repeat the test in 6 months   
 
The topics included in grids for focus groups with pharmacists will be:  
− 
Satisfaction of the HIV test delivery: feeling at ease, time-consuming, contact with 
participants, logistical issues    
− 
Willingness to sustain the strategy, perception and improvement of the strategy   
 
Withdrawal of consent and loss to follow-up  
Consent withdrawal 
A participant will be considered to have withdrawn consent if s/he no longer wishes to 
remain in the study. In this case, a “withdrawal of consent form” could be filled in the external 
website. 
When a participant who withdraws consent explicitly expresses the will that his/her data be 
removed from the database and his/her laboratory samples be destroyed, the study team will 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 21/52 
carry out such will. When a patient who withdraws consent do not express such will, data and 
samples collected prior to the date of his/her consent withdrawal will be used for the analysis. 
Loss to follow-up 
When a participant who has not explicitly withdrawn consent does not return the HIVST 
result after one week, the research team will reach them by phone. Also, 1 week after returning 
positive HIVST results, if there is no information confirming the linkage to one of the partner ART 
sites or participant does not show up after receiving the reminder for 6-month HIVST, the 
research team will reach them by phone.  
A participant who does not show up for a given schedule and the study team failed to reach 
by phone will be considered lost-to-follow-up.  
 
10 LABORATORY EVALUATIONS 
Samples collection and tests 
The HIV Self-test used in the study is OraQuick® which is a private and rapid HIV tests using 
oral fluid with safe, accurate, and quick results.  
The OraQuick ® HIV Self-Test uses oral fluid to check for HIV-1 and HIV-2 antibodies. It give you 
results in about 20 minutes, and can detect the virus in over 99% percent of people who are 
infected with HIV. Because the test is a "screening" test, it is always advised to have a second test 
to confirm the results and participants will be referred for that purpose in case of reactive 
HIVST.  
Biobank 
 
Not applicable.  
11 ADVERSE EVENTS AND IN UTERO EXPOSURE 
Not applicable.   
12 SCIENTIFIC BOARDS AND COMMITTEES 
a) Scientific Advisory Board (SAB) 
Composition 
 
The SAB will consist of: (i) the investigators, the study, clinical coordinators  and 
statisticians/methodologists of the study; (ii) representative members of the community-based 
organizations; (iii) a representative of the NCHADS; (iv) a representative of partner pharmacies 
(v) other external experts; and  (vi) sponsor representatives.  

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 22/52 
 
Meeting agenda 
 
The SAB will meet before the beginning of the inclusion phase, as well as once or twice per year 
until the end of the study. The sponsor or one or several board members may also request a 
special meeting at any time. 
 
Role 
 
The role of the SAB is to ensure that the study is carried out appropriately, not only scientifically 
but also clinically and ethically. The members of the SAB report directly to the sponsor. 
• 
They will ensure that the study personnel carry out the study properly, adhere to the 
protocol and maintain patient safety; 
• 
They will guarantee that the study remains scientifically relevant by ensuring the 
relevancy of the study questions and that the methods used are valid and appropriate; 
• 
They will make all decisions regarding necessary and relevant protocol modifications, 
such as:  
o Actions needed to facilitate patient recruitment; 
o Decisions to open or close participating study sites. 
• 
They will enforce the rules pertaining to access to the study data as well as reports and 
publications of the results; 
• 
They will remain in contact with the sponsor, and the coordinating investigators, and 
will make sure investigators and other personnel have access to up-to-date information. 
At the end of each meeting, a report containing the meeting minutes, signed by the SAB Chair 
will be sent to the members of the SAB, and the director of ANRS EID.  
13 COORDINATION, MONITORING, DATA MANAGEMENT  
Coordination 
 
The Grant Management Office (GMO) of the UHS is the referent for the study’s methodology and 
management. The GMO is responsible, in coordination with the clinical and administrative 
coordinators, for the overall study management (preparation and organisation of the study, 
monitoring, data management and analysis). Research activities will be coordinated and 
monitored by a Project Manager who will work in close collaboration with the 2 coordinating 
investigators and the clinical coordinator. These activities include notably: 
- Recruitment, training and management of the clinical research assistants (CRAs) and of 
the community workers;  
- Organising and supporting inclusion and follow-up of patient on site;   
- Coordinating Monitoring and data-management activities; 
The Project Manager will hold regular meetings with the CRAs and the community workers, from 
the first pre-inclusion until the end of the study. 
The goals of these meetings will be: 
- 
To verify that the study is being carried out in accordance with the protocol, SOP and Good 
Clinical Practice 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 23/52 
- 
To verify that all inform consent forms are valid 
- 
To verify that confidentiality of data is fully respected  
- 
To discuss difficult patient files, and facilitate patient care in case of positive HIVST, in 
collaboration with the Clinical Coordinators 
- 
To discuss any file that the research team estimate as problematic after having reviewed 
the trial database.  
The sponsor mandates the GMO to coordinate the research. The delegation of tasks between  GMO 
members, coordinating investigators, sponsor and study site teams is specified in a signed 
agreement under the supervision of the Sponsor. This document can be revised as often as 
necessary. The GMO works in close coordination with the Clinical Research Department of the 
ANRS. The GMO is responsible for the preparation of the research including training, logistic, 
patient monitoring, data collection and analysis. The GMO is responsible for monitoring the 
compliance with the protocol, the GCP-ICH and the study procedures. 
• Preparation and organisation of the study: the UHS team will finalize and review the 
study documents (including; protocol, information sheet and consent form,  electronic 
Case Report Forms (e-CRF), table grids for FG (annexe 4&5), and all the Standard 
Operating Procedures), prepare the recruitment procedures, and organize the training for 
the CRAs and the community workers.  
• Website and Database: will be developed and managed by IT office at UHS. 
• Data analysis and analysis report: will be coordinated at the UHS coordinating centre.  
• Reporting: the operational team will be responsible for finalizing:  
- 
the necessary reports and presentations for the Scientific Advisory Board;  
- 
the study yearly progress reports; The operational team will bring its 
support in preparing any communications on the research study (poster, 
oral presentation, papers).  
Study documents 
 
Essential study documents (protocol, case report forms, SOPs, etc) and regulatory (ethical 
clearance, task delegation, agreements, curriculum vitae, etc..) will constitute the Trial Master File 
(TMF). The TMF will be held at the GMO located at the UHS and will be retained for 15 years.  
Each investigator will keep a hard copy of relevant TMF documents in an Investigator Site File 
(ISF). The Clinical Research Assistants (CRAs) will be responsible for checking that the documents 
contained in the ISF of each study site are up-to-date.  
Data management  
The UHS Team will be responsible, on behalf of the sponsor, for implementation of procedures 
for data collection, storage, protection, retention and destruction. The team has implemented a 
data safety and security concept according to the requirements. All related procedures will be 
developed in cooperation with the data security engineer of the UHS team and have to be 
approved by the official data protection officer of the University of Health Sciences prior to 
implementation. 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 24/52 
Data collection  
Data from participants will be collected in partner pharmacies, after signature of Informed 
consent, in tablets on electronic case report forms (e-CRF). The community workers will be 
responsible for filling out data into the e-CRF. A unique e-CRF will be assigned for each 
participant. The participant will only be registered through a unique confidential code.  
A Standard Operating Procedure (SOP) will be provided to guide the community workers to fill 
out the e-CRF. All information required by the protocol should be provided and any omission 
would require explanation. 
The CRAs are responsible for ensuring that all sections in the e-CRF are completed correctly and 
that number of entries can be verified with the number of HIVST delivered in each pharmacy. 
The results of the HIVST will be recorded by the participants on the external website with the 
unique ID.  
Data entry and checking  
Data will be entered on a regular basis at the GMO from tablets to the database. After data entry, 
the database will be checked for consistency. The data manager will implement data 
management programs to ensure completeness, consistency and reliability of data. All 
consistency test will be designed according to the proposition of a team constituted of the 
Coordinating Investigators, the project manager and the data Manager. If any inconsistency or 
question related to the collected data, the CRAs will go back to the community workers for 
clarification during the monitoring visit. The corrections will be entered and followed in the 
database with traceability of the corrections.  
Methods to ensure restricted access to the database; and the data management procedures, 
including the procedures to verify the completeness, accuracy, quality and validity of the data, 
will be described in specific trial SOPs.  
Data storage 
All data and software will be physically stored in dedicated data centers. Data will be physically 
stored in a MySQL Server. 
All software are hosted on certified virtual servers running Linux Enterprise in a VMWare 
environment. There are several dedicated servers for each system, ensuring separation between 
the testing / pre-production environment and the production environment. System updates are 
applied only after validation in the pre-production environment.  
For security reasons, the application tiers and the database management systems run 
independently in separate servers.  
All exploitation, monitoring and backups operations are performed by UHS Team, in accordance 
with UHS policies.  
All systems and applications are continuously monitored. Appropriate measures are 
automatically taken whenever an alert is issued. 
Data protection 
Data Access 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 25/52 
An access concept for the database will be implemented, based on the roles and permissions. 
Thus, data access will be limited to authorized persons only, and unauthorized access to 
anonymized data will be prevented. 
Any change of data (e.g. error correction during query management) will be recorded 
automatically via an audit trail within the database.  
At the end of the study, once the database has been declared complete and accurate, the 
database will be locked.  
Data Tracking 
All modifications during the study conduct will be tracked. Data will be electronically and 
systematically revalidated after each major change, and corrections/completeness applied 
whenever necessary.  
All system log-ins, interventions, modifications and form status changes will be thoroughly 
recorded in an Audit Trail log system.  
Data Export 
Data and metadata will be exported in due time in plain text CSV or STATA formats. These 
exports might be post-processed programmatically by UHS team to facilitate data analysis and 
data visualisation.  
Data Security  
Physical access to the data centers is logged and limited to authorized personnel using badge 
authentication. On a regular basis, vulnerability testing is performed to reduce potential 
exposure.  
Remote access to servers is limited to authorized personnel. Connections to servers are 
encrypted using SSH. System logs are stored in a dedicated centralized system for audit 
purposes. The internal network is protected by multiple firewalls, proxy, reverse-proxy and anti-
virus solutions.  
Web servers operate under SSL (HTTPS) certifications, ensuring Web connections are encrypted 
and secure.  
At the Database level, only people part of the investigation team, the sponsor team, the affiliated 
reviewers or auditors, as well as inspection authorities are given access to data. Personal 
accounts are granted individually for each person. Identification is made by a personnel ID and a 
password. Failure to provide the correct password after a limited number of attempts 
automatically deactivates the faulty account (protection against non-authorized attacks).  
 
Data Safety  
 
Backups operations are performed by the UHS Team service at UHS, in accordance with UHS 
policies.  
Backup strategy compromises an optimized daily, monthly and yearly retention plan:  
For Website and Study Database 
• 
Server backups :1x differential per day (24 days retention), 1x full every 24 days 
(retention 12 months), annual (preserved infinitely)  

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 26/52 
• 
Database backups : every day, with 2 full backups twice per week (double copies, 2 
months retention for Sunday backups, and 14 days for the others), log backups every 
hour (2 months retention)  
• 
For Database Management System and Administrative Database 
• 
Server backups : 1x differential per day (14 days retention, with mirroring), 1x full every 
month (retention 12 months), annual (preserved infinitely)  
• 
Database backups : every day, with 2 full backups twice per week (double copies, 2 
months retention for Sunday backups, and 14 days for the others), log backups every 
hour (2 months retention) 
Monitoring  
Monitoring will be conducted according to the Good Clinical Practice (ICH Harmonized 
Tripartite Guidelines for Good Clinical Practice 1996) to guarantee the good quality of the 
research and safeguard the health and the rights of the participants.  
The monitoring plan is established by the GMO with the Sponsor and the Coordinating 
Investigators before the beginning of the study.  
The CRAs will come on a regular basis at the partner pharmacies to check for completeness, 
accuracy and legibility of data reported on the e-CRF. They will check the consistency between 
the e-CRF filled and the number of HIVST delivered. The pharmacist shall give to the CRA access 
to relevant pharmacy stock records, to confirm their consistency with the CRF entries. No 
information about the identity of the subjects should appear on the CRF. All CRF must be signed 
by the community workers in charge of the participant inclusion and/or follow-up. E-CRF will be 
considered as a source document for all the study sites regarding all the information it contains.  
 
Monitoring activities will be coordinated by the GMO. The CRA(s) will visit the site regularly 
during the study, including during set up, implementation, and at the end of the trial:  
- 
To establish and maintain up-to-date the Investigator’s site Files (ISF) and Trial Master 
File (TMF) 
- 
To verify that all inform consents are valid 
- 
Check the adherence to the protocol, SOPs and to Good Clinical Practice (patient 
informed consent, eligibility criteria, e-CRF filling, HIVST storage and dispensation …);  
- 
To check the study organisation and management on site (communication between 
participants, pharmacists and community workers, confidentiality during e-CRF filling, 
HIVST availability);  
- 
Evaluate the progress of enrolment;  
- 
Check the completeness and the accuracy of patient data on the e-CRF;  
- 
To verify that confidentiality is fully respected   
- 
Check that the storage and dispensation of HIVST respect the study protocol and 
dedicated SOP 
14 STATISTICAL ANALYSES 
Calculation of number of participants needed 
We will use a pragmatic approach with the objective to recruit the maximum of MSM and TGW. 
According to the IBBS 2019, the estimated number of MSM in Phnom Penh is 6300 and the 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 27/52 
estimated number of TGW is 1400. 
With 1500 participants (1000 MSM and 500 TGW), we will be able to estimate an HIV self-test 
uptake of 70% to within a 95% confidence interval of +/- 2 – 2.5% (width of the confidence 
interval (in %) = 1.96 x √( p x (1-p) / n). 
 
Analysis plan 
Description of the characteristics at inclusion.  
 
These variables will be described by their median, interquartile range, mean, standard deviation, 
or frequencies (%), as appropriate. These variables will be compared to those reported in the 
IBBS 2019 for MSM and TGW.  
 
Primary outcome  
 
The percentage, and its 95% confidence interval of HIV self-tests delivered among the total 
number of coupons distributed will be given and stratified by gender (MSM or TGW) and by type 
of coupons (paper or electronic). 
 
Secondary outcomes 
 
• 
The percentage and its 95% confidence interval of HIVST result’s recorded among the 
total number of HIVST delivered will be given and stratified by gender (MSM or TGW) 
• 
For those accepting to be contacted by phone, the percentage and its 95% confidence 
interval of HIVST realized among the number of HIV tests results non recorded will be 
given   
• 
The percentage and its 95% confidence interval of participants with positive HIV self-
tests linked to an ART site will be given and stratified by gender (MSM or TGW)   
• 
The percentage and its 95% confidence interval of participants with negative HIV self-
tests linked to PrEP services will be given and stratified by gender (MSM or TGW)  
• 
The percentage and its 95% confidence interval of participants with 6-monthly repeated 
HIV testing during the 18 months (so 4 HIVSTs during the total duration of the study) 
will be given  
• 
The probability of discontinuation of HIV testing and its 95% confidence interval, as well 
as the median time to the occurrence of HIV testing discontinuation, will be determined 
using a Kaplan Meier analysis, to take into account censored data due to lost of follow-
up.   
 
For qualitative assessment, bilingual research staff transcribed all interviews verbatim and 
translated them into English. We used both inductive and deductive approaches when analysing 
the data. Inductive analysis was used in the early stage to explore the ideas and meanings 
contained in the raw data and to identify concepts, patterns and themes. Similar codes were 
collated to form initial themes. Once patterns, themes and subthemes were established by open 
coding, deductive content analysis was used to validate these in an iterative process. We 
reported the results in participant-based, and provider-based issues. QSR NVivo V.12 for 
Windows was used to manage the data. 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 28/52 
15 SCIENTIFIC COMMUNICATION 
All written or oral communications of the study’s results must receive the approval of the 
coordinating investigators and of the SAB of the study.  
The GMO will realize data analysis. This analysis will lead to a report, submitted to the SAB for 
approval. This report will help to prepare scientific publications whose final draft must be 
approved by the SAB .  
All publications will include the name of sponsor as follows ("ANRS-MIE. The French National 
Agency for Research in HIV/AIDS, Viral Hepatitis and Emerging Infectious Diseases is the sponsor 
of the project") followed by the ANRS study number (ANRS 0100s + Acronym).  
In case of ancillary studies, results will be published after approval by SAB. In addition, these 
results will be published only after the publication of the main results obtained during the 
research project. Results obtained through ancillary studies will be also transmitted to ANRS-MIE 
for information. 
16 ETHICS AND LEGAL CONSIDERATIONS  
• 
16.1. Ethics 
 
This research project will be conducted with regard to fundamental ethical principles that are 
described in the updated version of the Declaration of Helsinki (64th World Medical Association 
[WMA] General Assembly, Fortaleza, Brazil, October 2013), and in the ANRS ethics charter for 
research in developing countries (July 2017) (http://www.anrs.fr/Ressources-et-
publications/Publications/Publications-ANRS/Charte-d-ethique-de-la-recherche-dans-les-pays-
en-developpement). 
 
• 
16.2. Policies and legal aspects 
 
This study will be conducted in conformity with the French Public Health Code, as modified, 
notably, by Public Health Low no 2004-806 of August 9, 2004 and its subsequent texts, and the 
Law n° 2012-300 of March 05th 2012 on research involving the human person (‘Jardé Law’) and 
its subsequent texts. 
This research project will be also conducted in accordance with national regulations and laws in 
Cambodia, and according to E6 Good Clinical Practice (GCP). 
The protocol, information sheet, and informed consent (appendix 1 and 2) will receive the 
approval from the National Ethics Committee for Health Research (NECHR). The written NECHR 
approval must be made available to the legal sponsor before the study can start. The sponsor or 
its delegate is, together with the investigator, responsible for submission to and communication 
with the NECHR as well as for obtaining approval of all subsequent major changes, in 
compliance with local law. 
 
The research will be performed according to the present protocol. All researchers and 
investigators participating to this project will respect the protocol, especially in obtaining 
informed consent (see below). 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 29/52 
• 
16.3. Information and consent 
Participation in the study is voluntary. The consent of each potential participant is a prerequisite 
before starting any sampling or before obtaining any specific information related to the research 
project. The informed consent must be signed by each participant after giving full research 
description:  
- 
What is being studied?  
- 
What is the procedure/protocol?  
- 
Who is sponsoring the study?  
- 
What are the risks and burdens? 
- 
What are the benefits? 
- 
Whom to contact with questions/concerns 
The person in charge of informed consent process at the trial site will read out and explain the 
information notice to the patient in his/her language, and will answer any questions that may 
arise. Each potential participant will be given time to think about the information before making 
a decision. 
Each subject must fully understand that they have the full freedom to accept or refuse to 
participate in the study. Once one subject is included in the research project, he has to 
understand that he can also withdraw from it whenever he wants without any 
problems/consequences and he will continue to benefit from the regular medical care and 
check-up. 
When one person gives his/her consent for participating to the study, he (she) will write his 
(her) last name and first name, date and sign the informed consent.  
Each signed informed consent will be kept in a safe manner and in a safe place for a total 
duration of 15 years after the end of the research project.  
 
• 
16.4. Data confidentiality 
 
All information collected from enrolled subjects will be strictly confidential and coded. 
Investigators will make individual data available upon request by representatives of the sponsor 
and representatives of the ethical and regulatory health authorities, for monitoring purposes or 
in the event of external audit or inspection. Disclosure to other third parties is strictly 
prohibited. All persons having access to the data, including the investigator, are subject to the 
obligation of professional secrecy. 
During the implementation and by the end of the research, information collected among 
participants must be de-identified and names, personal addresses must not be indicated in any 
document brought back to the GMO. 
For this purpose, each participant will receive a unique identification number. This code will be 
the only patient identifier on any document related to the study, as well as in the electronic 
study database. There will be no link between the name of the patient and his/her personal 
identifier in the database.  
 
• 
16.5. Data processing 
 
All data obtained through this research project will be recorded in a database at GMO (UHS). The 
Sponsor Inserm-ANRS |MIE in collaboration with GMO, study coordinator and investigators  will 
prepare all the necessary documentations in the purpose to obtain the required authorization 
from the French National Commission of Informatic and Liberty (CNIL).  
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 30/52 
• 
16.6. Final report 
 
The official date for the end of the study is the date of the last visit of the last participant. 
 
The sponsor or its representative will notify the end of the study to the NECHR within 90 days.  
A premature end may be decided by the sponsor, following the advice of the SAB, or the ethical 
authority. In case the study is ended prematurely, the sponsor or its representative will notify 
the ethical authority within 15 days, and clarify the reasons for such a premature termination. In 
this case, the sponsor and the investigators, in close collaboration with the country health 
authority, will take appropriate decision to ensure that patients have access to the best available 
care and treatment according to the country condition. 
 
GMO will write the final report, in partnership with principal investigators, as well as summary 
report, one year after the end of the research and will transmitted them to ANRS. Within one 
year after the end of the study, the sponsor or its representative will release to the ethical 
authority the final study report and/or summary including the results of the study and the 
scientific publications or communications related to these results available at this time.  
 
The report and its summary are established according to ICH recommendations (International 
Conference for Harmonisation – ICH Topic E3 – Structure and Content of Clinical Study Reports 
CPMP/ICH/137/95. Accessible at: 
https://database.ich.org/sites/default/files/E3_Guideline.pdf). 
 
 
• 
16.7. Archiving system 
 
Forms and data related to the research project are key documents. They can be useful to 
demonstrate that researchers and investigators respect GCP and current laws/legislation. 
Consequently, all these documents will be archived by GMO and ANRS during 15 years after the 
end of the research program. 
Informed consents will be kept in a safe manner at GMO in sealed envelopes on which ID 
numbers of the participants will be indicated, as well as name and signature of the coordinating 
investigators. 
No documents must be destroyed without prior authorization from ANRS. 
 
17 ACCESS TO DATA AND SPECIMENS 
 
All collected data related to the study protocol will be under the GMO’s responsibility from the 
beginning to the end of the trial. After the end of the trial, the GMO will remain responsible for 
the database, until otherwise decided by the sponsor. 
 
Data will be utilized according to this protocol. Any utilization for analysis not listed in the 
protocol should be approved by the trial coordinating investigators and either the SAB (if the 
study is still ongoing) or the sponsor (if the study is terminated). 
 

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 31/52 
After the analysis and publication of the study results, the data will be made available to 
investigators and external researchers to maximize the impact of the data by encouraging 
secondary analysis to address other research questions. The clear process for data access will be 
developed with the sponsor in the dissemination and exploitation plan to ensure transparency 
and accountability of data requestors, and the data release decision making process. Policies will 
be developed to assure that those who re-use data duly credit those who produced the data. The 
requestor should be explicit about the proposed research use of data, including the justification 
for the specific datasets requested. The shared data will be formatted to the required standards 
for sharing once defined by the SAB. 
 
18 DUTIES OF INVESTIGATORS 
 
According to GCP aimed to achieve high quality of the research, each investigator must: 
- 
To respect participants’ rights and to ensure subjects’ welfare, 
- 
To ensure his availability as well as availability of his team, 
- 
To ensure that enrollment will be feasible according to the research protocol, 
- 
To organize technical infrastructures for the implementation of sampling, filling in of 
questionnaires and archiving of documents/records during the research study and 15 
years after the end of the research, 
- 
To collect and archive in a safe way signed informed consents, 
- 
To ensure that researchers are following the protocol and to allow completed 
questionnaires to be regularly sent to GMO,  
- 
To accept a possible audit of the research project carried out by ANRS itself or by other 
agencies if necessary. 
 
19 REFERENCES 
1.  
UNAIDS DATA 2019 [Internet]. Disponible sur: 
https://www.unaids.org/en/resources/documents/2019/2019-UNAIDS-data 
2.  
Griensven F van, Guadamuz TE, Wijngaarden JW de L van, Phanuphak N, Solomon SS, Lo Y-R. 
Challenges and emerging opportunities for the HIV prevention, treatment and care cascade in men 
who have sex with men in Asia Pacific. Sex Transm Infect. 1 août 2017;93(5):356‑62.  
3.  
2013 Annual Update [Internet]. Asia Pacific Coalition on Male Sexual Health; Disponible sur: 
https://www.apcom.org/wp-content/uploads/2016/01/2013-APCOM-Annual-Update.pdf 
4.  
HIV and AIDS in Asia & the Pacific regional overview [Internet]. Avert. 2015 [cité 23 nov 
2021]. Disponible sur: https://www.avert.org/professionals/hiv-around-world/asia-pacific/overview 
5.  
UNAIDS - KEY POPULATIONS ATLAS [Internet]. [cité 24 nov 2021]. Disponible sur: 
https://kpatlas.unaids.org/dashboard 
6.  
Chhim S, Ngin C, Chhoun P, Tuot S, Ly C, Mun P, et al. HIV prevalence and factors associated 
with HIV infection among transgender women in Cambodia: results from a national Integrated 
Biological and Behavioral Survey. BMJ Open. août 2017;7(8):e015390.  

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 32/52 
7.  
Yi S, Chhim S, Chhoun P, Tuot S, Ly C, Mun P, et al. Men Who Have Sex with Men in 
Cambodia: Population Size, HIV Risky Behaviors, and HIV Prevalence. American Journal of 
Epidemiology and Infectious Disease. 2016;4(5):10.  
8.  
Yi S, Ngin C, Tuot S, Chhoun P, Chhim S, Pal K, et al. HIV prevalence, risky behaviors, and 
discrimination experiences among transgender women in Cambodia: descriptive findings from a 
national integrated biological and behavioral survey. BMC Int Health Hum Rights. déc 2017;17(1):14.  
9.  
NCHADS and FHI-360. Integrated Biological and Behavioural Survey among Men Who Have 
Sex with Men and Transgender Women in Cambodia 2019. NCHADS and FHI-360;  
10.  
World Health Organization. WHO RECOMMENDS HIV SELFTESTING – EVIDENCE UPDATE AND 
CONSIDERATIONS FOR SUCCESS [Internet]. World Health Organization; 2019. Disponible sur: 
file:///C:/Users/Sovanthida/Downloads/WHO-CDS-HIV-19.36-eng.pdf 
11.  
WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing 
HIV infection - recommendations for a public health approach. 2nd éd. World Health Organization; 
2016.  
12.  
Katz DA, Golden MR, Hughes JP, Farquhar C, Stekler JD. HIV Self-Testing Increases HIV Testing 
Frequency in High-Risk Men Who Have Sex With Men: A Randomized Controlled Trial. JAIDS Journal 
of Acquired Immune Deficiency Syndromes. 15 août 2018;78(5):505‑12.  
13.  
Saul H, Gursul D. Self-testing for HIV could increase diagnoses in the trans community. BMJ. 
10 nov 2021;375:n2633.  
14.  
Thirteen countries from Asia and the Pacific plan scale-up of PrEP and HIV self-testing 
[Internet]. Unitaid. [cité 24 nov 2021]. Disponible sur: https://unitaid.org/news-blog/thirteen-
countries-from-asia-and-the-pacific-plan-scale-up-of-prep-and-hiv-self-testing/ 
15.  
NCHADS. National Consolidated Guidelines on HIV Testing Services in Cambodia. 2017.  
16.  
Evaluation of the Boosted- Integrated Active Case Management (B-IACM) in Cambodia. 2017 
oct.  
17.  
Pal K, Ngin C, Tuot S, Chhoun P, Ly C, Chhim S, et al. Acceptability Study on HIV Self-Testing 
among Transgender Women, Men who Have Sex with Men, and Female Entertainment Workers in 
Cambodia: A Qualitative Analysis. Andrei G, éditeur. PLoS ONE. 9 nov 2016;11(11):e0166129.  
18.  
World Health Organization. HIV self-testing: key questions, answers and messages for 
community organizations [Internet]. World Health Organization; 2018 [cité 24 nov 2021]. Report No.: 
WHO/CDS/HIV/18.23. Disponible sur: https://apps.who.int/iris/handle/10665/273771 
19.  
Self-Testing: a convenient and private option [Internet]. 2021 [cité 24 nov 2021]. Disponible 
sur: https://www.cdc.gov/hiv/basics/hiv-testing/hiv-self-tests.html 
20.  
Autotests de dépistage de l’infection par le VIH [Internet]. 2015 [cité 23 nov 2021]. 
Disponible sur: https://www.has-sante.fr/jcms/c_1768844/fr/autotests-de-depistage-du-vih 
21.  
GUIDELINES ON HIV TESTING SERVICES HIV SELF-TESTING AND PARTNER NOTIFICATION 
SUPPLEMENT TO CONSOLIDATED GUIDELINES ON HIV TESTING SERVICES. World Health Organization; 
2016.  
22.  
Bryant J. Using respondent-driven sampling with ‘hard to reach’ marginalised young people: 
problems with slow recruitment and small network size. International Journal of Social Research 
Methodology. 2 nov 2014;17(6):599‑611.  
23.  
Lachowsky NJ, Lal A, Forrest JI, Card KG, Cui Z, Sereda P, et al. Including Online-Recruited 
Seeds: A Respondent-Driven Sample of Men Who Have Sex With Men. J Med Internet Res. 15 mars 
2016;18(3):e51.  

 
 
ANRS 0100s - Protocol -                                                                          Version 1.1 du 18/04/2022 
 
Page 33/52 
24.  
Weiss KM, Jonas KJ, Guadamuz TE. Playing and Never Testing: Human Immunodeficiency 
Virus and Sexually Transmitted Infection Testing Among App-Using MSM in Southeast Asia. Sexual 
Trans Dis. juill 2017;44(7):406‑11.  
25.  
De Boni RB, Veloso VG, Fernandes NM, Lessa F, Corrêa RG, Lima RDS, et al. An Internet-Based 
HIV Self-Testing Program to Increase HIV Testing Uptake Among Men Who Have Sex With Men in 
Brazil: Descriptive Cross-Sectional Analysis. J Med Internet Res. 1 août 2019;21(8):e14145.  
26.  
Strömdahl S, Lu X, Bengtsson L, Liljeros F, Thorson A. Implementation of Web-Based 
Respondent Driven Sampling among Men Who Have Sex with Men in Sweden. PLoS One. 
2015;10(10):e0138599.  
27.  
Bengtsson L, Lu X, Nguyen QC, Camitz M, Hoang NL, Nguyen TA, et al. Implementation of 
web-based respondent-driven sampling among men who have sex with men in Vietnam. PLoS One. 
2012;7(11):e49417.  
28.  
Huang E, Marlin RW, Young SD, Medline A, Klausner JD. Using Grindr, a Smartphone Social-
Networking Application, to Increase HIV Self-Testing Among Black and Latino Men Who Have Sex 
With Men in Los Angeles, 2014. AIDS Educ Prev. août 2016;28(4):341‑50.