A Multicenter, Observational Cohort to Study the Characteristics of Individuals Asking for Pre-exposure Prophylaxis (PrEP) and the Incidence of HIV and Other Sexually Transmitted Infections: 'The SwissPrEPared Study'
Conditions: HIV Preexposure Prophylaxis
Sponsor: University of Zurich

Project Title
A multicenter, observational cohort to study the characteristics of 
individuals asking for pre-exposure prophylaxis (PrEP) and the 
incidence of HIV and other STIs: ‘The SwissPrEPared Study’
Research legislation:
Ordinance on human research with the exception of Clinical trials 
(HRO) [1].
Type of Research Project:
Research project involving human subjects 
Risk Categorisation:
Category A
Sponsor Investigator:
Prof. Dr. med. Jan Fehr
University of Zürich
Epidemiology, Biostatistics and Prevention Institute
Department Public Health
Hirschengraben 84
CH 8001 Zurich
Principal Investigator:
Dr. med. Benjamin Hampel
Coordinating study center: 
University of Zurich
Epidemiology, Biostatistics and Prevention Institute
Department Public Health
Local project leaders at 
participating study canters:
SHCS center and Checkpoint Bern: Dr. Christoph Hauser
SHCS center Geneva: Prof. Alexandra Calmy
SHCS center Lausanne: PD Dr. Matthias Cavassini
SHCS center St.Gallen: Prof. Pietro Vernazza
SHCS center Zurich: Dr. Dominique Braun
SHCS center Basel: Dr. Marcel Stöckle
SHCS center Lugano: Prof. Enos Bernasconi
Checkpoint Geneva: Dr. Victor Pecoul
Checkpoint Lausanne: Dr. Vanessa Christinet
Checkpoint Zurich: Dr. Benjamin Hampel
Medical Center Kalkbreite, Zurich: Dr. Carsten Depmeier
Dermatological Center Zurich: PD Dr. Severin Läuchli
Project plan template
Human research other than clinical trials
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PROTOCOL SIGNATURE FORM 
Study Title
A multicenter, observational cohort to study the characteristics of 
individuals asking for pre-exposure prophylaxis (PrEP) and the 
incidence of HIV and other STIs: ‘The SwissPrEPared Study’
The project leader (main center) and the investigator (at the local center/site) have approved the 
protocol version [1.0 (dated 24.10.2018)], and confirm hereby to conduct the project according 
to the protocol, the Swiss legal requirements [1,2], the current version of the World Medical 
Association Declaration of Helsinki [3] and the principles of Good Clinical Practice.
Project leader (lead center/site)
Site: University of Zurich, Department Public Health
Local Project Leader at local center/site:
Site: SHCS center Basel
Site: SHCS center and Checkpoint Bern
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Site: SHCS center Geneva
Name of Local Project Leader:  Prof. Alexandra Calmy
Date:
25.10.2018                              Signature:
Site: SHCS center Lausanne
Name of Local Project Leader: PD Dr. Matthias Cavassini
Site: SHCS center Lugano
Name of Local Project Leader:  Prof. Enos Bernasconi
Date:
Signature:
Site: SHCS center St.-Gallen
Name of Local Project Leader: Prof. Pietro Vernazza
Site: SHCS center Zurich
Name of Local Project Leader:  Dr. Dominique Braun
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Site: Checkpoint Geneva
Site: Checkpoint Lausanne
Name of Local Project Leader: Dr. Vanessa Christinet
Site: Checkpoint Zurich
Site: Private medical centre (Arztpraxis Kalkbreite, Zurich)
Site: Dermatological Center Zurich (Dermatologisches Zentrum Zürich)
Name of Local Project Leader: PD Dr. Severin Läuchli
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TABLE OF CONTENTS
TABLE OF CONTENTS
5
GLOSSARY OF ABBREVATIONS
6
1
BACKGROUND AND PROJECT RATIONALE
7
2
PROJECT OBJECTIVES AND DESIGN
10
2.1 Hypothesis and primary objectives
10
2.2 Primary endpoints
12
2.3 Project design
12
3
PROJECT POPULATION AND STUDY PROCEDURES
13
3.1 Project population, inclusion and exclusion criteria
13
3.2 Recruitment, screening and informed consent procedure
13
3.3 Study procedures
15
3.4 Withdrawal and discontinuation
17
4
STATISTICS AND METHODOLOGY
17
4.1. Statistical analysis plan
17
4.2. Handling of missing data
18
5
REGULATORY ASPECTS AND SAFETY
19
5.1 Local regulations / Declaration of Helsinki
19
5.2 Notification of safety and protective measures (HRO Art. 20)
19
5.3 Serious events (HRO Art. 21)
19
5.4 Amendments
19
5.5 End of project
19
5.6 Insurance
20
6
FURTHER ASPECTS
20
6.1 Overall ethical considerations
20
7
QUALITY CONTROL AND DATA PROTECTION
21
7.1 Quality measures
21
7.2 Data recording and source data
21
7.3 Confidentiality and coding
21
7.4 Retention and destruction of study data and biological material
22
8 FUNDING / PUBLICATION / DECLARATION OF INTEREST
22
9
REFERENCES
23
10 APPENDIX
24
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GLOSSARY OF ABBREVATIONS
ART
Antiretroviral Therapy
BASEC
Business Administration System for Ethical Committees
CRF
Case report form
ECDC
European Centre for Disease Prevention and Control
EMA
European Medicines Agency
FCSH
Federal Commission for Sexual Health
FDA
Food and Drug Administration
FOPH
Federal Office of Public Health
FSW
Female Sex Worker
HIV
Human Immunodeficiency Virus
HRA
Human Research Act
HRO 
Ordinance on Human
MSM
Men having Sex with Men
PrEP
Pre-exposure prophylaxis
SHCS
Swiss HIV Cohort Study
STIs
Sexually Transmitted Diseases
TDF/FTC
Tenofovir/emtricitabine
UNAIDS
Joint United Nation Program on HIV/AIDS
STIs
Sexually Transmitted Diseases
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1
BACKGROUND AND PROJECT RATIONALE 
Preliminary note: the "SwissPrEPared Study" is nested within the "SwissPrEPared Program" 
(Figure 1). The "SwissPrEPared Program" is a nation-wide program for the surveillance and the 
exchange of experiences related to HIV pre-exposure prophylaxis (PrEP) consultations. The 
goal is to ensure the best care for individuals asking for PrEP. Data generated by the program 
will  be  used  to  explore  specific  research  questions,  hereinafter  referred  to  as  the 
“SwissPrEPared  Study”.  A  comprehensive  description  of  the  SwissPrEPared  Program 
procedures (program guidelines, visits, screening tests) is provided in a separate document 
(see “SwissPrEPared program description”).  
Figure 1: Relationship between the SwissPrEPared program and the SwissPrEPared study.
The  Swiss  HIV  prevention  program,  under  the  auspices  of  the  section  ‘prevention  and 
promotion’ of the Federal Office of Public Health (FOPH), has achieved a stabilization of the 
HIV epidemic in the past decade. Yet, each year, there is still a considerable number of newly 
detected HIV infections.1  
Pre-exposure  prophylaxis  (PrEP)  is  an  effective  measure  to  complement  existing  HIV 
prevention strategies among populations at risk of HIV infection (e.g. men having sex with men 
(MSM) or female sex workers (FSW)) for whom classic prevention tools (such as condom use 
for anal sex) are not sufficient. PrEP refers to the use of antiretroviral medication (ART) to 
prevent HIV negative individuals from acquiring HIV. Large trials have shown high efficacy of 
continuous2,3 or intermittent4 PrEP with tenofovir/emtricitabine (TDF/FTC) in MSM at very high 
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risk of HIV who adhere to the regimen. In these studies, MSM at very high risk were defined as 
having a large number of sexual partners with whom they engage in condomless sex, often 
under the influence of psychoactive substances, including alcohol. TDF/FTC was approved for 
PrEP by the United States Food and Drug Administration (FDA) in 2012 and the European 
Medicines Agency (EMA) in 2016. There is significant evidence that the introduction of PrEP 
helped further reduce the number of HIV transmissions in groups at high risk for HIV: in San 
Francisco, California, newly diagnosed HIV infections decreased from 453 in the year 2012 to 
255 new infections in 2015;5 in London, the number of new HIV diagnoses in MSM was 40% 
lower in 2016 than in 2015.6 In a recently published study, the introduction of PrEP in New 
South Wales, Australia, led to a rapid decline in HIV diagnoses by 35%.7 Although a causal link 
cannot be formally established, it is plausible that the use of PrEP substantially contributed to 
these reductions. 
Despite its lack of approval in Switzerland, PrEP use needs to be monitored carefully: data from 
social media (such as Facebook®, Grindr® or planetromeo®), from the European Centre for 
Disease Prevention and Control (ECDC), and from the European PrEP surveys (www.eatg.org) 
suggest that a growing number of people in Switzerland already use generic TDF/FTC. PrEP 
users  were  found  to  buy  TDF/FTC  through  online  pharmacies,  often  without  medical 
supervision. Studies conducted in Switzerland confirm these findings. Hampel et al. performed 
an online-survey on the MSM geosocial networking application Grindr® to collect data on the 
acceptance of PrEP among sexually active MSM in Switzerland.8 The authors identified a high 
proportion of MSM with a positive attitude towards PrEP. Out of 1’893 survey participants, 944 
individuals (50%) were considering starting PrEP within the next six months, and 1’474 (80%) at 
some point in the future. Eighty-two participants (4.3%) reported that they were currently taking 
PrEP, of whom 18 (22%) said that they were taking PrEP without medical supervision, and 
seven PrEP-users (9%) had not had an HIV test within the previous 12 months. Overall, 575 
(30%) of all participants reported that their last HIV test was performed more than 12 months 
ago. Although some existing health care structures (such as Checkpoints, infectious disease 
clinics and Swiss HIV Cohort Study (SHCS) centers) already started offering counselling for 
individuals interested in taking PrEP, many PrEP users from the Grindr® survey were unaware 
of these services. 
The lack of medical supervision in individuals taking PrEP remains also a relevant issue: aside 
from drug-related side effects (such as kidney failure), subsequent viral resistance may arise in 
those taking PrEP despite a latent, undiagnosed HIV infection.9 Almost one third of the Grindr®-
survey participants and nearly 10% of PrEP users did not undergo HIV testing in the previous 
12 months. 
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Furthermore, there have been concerns about the potentially harmful effects of PrEP on sexual 
behaviour and other sexually transmitted diseases (STIs). PrEP has been introduced in the 
context of a longstanding reduction in condom use,10 and many countries are experiencing an 
alarming increase in STIs such as syphilis, gonorrhoea and chlamydia.1,11,12 The PROUD trial 
showed evidence of sexual behavioural risk compensation, with 21% vs. 12% (p=0.03) of 
immediate vs. deferred PrEP recipients reporting non-condom sex with 10 or more partners.3 In 
demonstration  projects  monitoring  PrEP  implementation  in  the  US,  the  mean  number  of 
condom-protected episodes of receptive anal sex decreased over the first 48 weeks.13 HIV-
uninfected MSM using PrEP and HIV-infected MSM with undetectable viral load on ART can 
disclose  and  use  this  information  on  geosocial  networking  apps  to  choose  partners  for 
condomless sex (biomed-matching).14 PrEP may therefore result in changes in sexual practices, 
which might ultimately facilitate STI transmission. On the other hand, studies modelling the 
impact of a PrEP program (i.e. regular STI screening and subsequent treatment) revealed an 
overall decline in the incidence of STIs, even if the probability of condom use was reduced.15 
Finally, participation to a PrEP program has been found to yield other health-related benefits for 
marginalized groups, such as more frequent screenings for depression, tobacco or diabetes, 
and an increased vaccination rate.16 
There is thus an urgent need to build up a comprehensive PrEP program in Switzerland, serving 
as an official platform for the surveillance and the exchange of experience related to PrEP 
prescription, and offering targeted prevention measures to individuals at higher risk of HIV 
infection (Figure 2). 
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Ultimately, the “SwissPrEPared Study” intends to provide a better understanding of the needs, 
expectations and vulnerabilities of individuals asking for PrEP. Study findings are expected to 
yield more efficient and better-targeted prevention measures directed at individuals at high risk 
of HIV infection. 
The “SwissPrEPared Study” has been deemed “category A” research project according to art.7 
(HRO),  as  data  collection  only  entails  minimal risks  and  burden.  The  ethical  rationale  is 
described under section 6 of this document. 
1
PROJECT OBJECTIVES AND DESIGN 
Nested within the SwissPrEPared Program, the “SwissPrEPared Study” – a large, multicentric, 
nation-wide cohort study – aims to longitudinally follow individuals asking for PrEP prescription 
over a period of 3 years. 
The main aims of the study will be:
1.  To  obtain  epidemiological  data on  individuals  asking  for  PrEP  in  Switzerland.  We are 
particularly interested in:

Determining the extent of PrEP use in Switzerland; 

Assessing and monitoring the occurrence of STIs in this particular population.
2. To assess  sexual health and sexual well-being in individuals  asking  for PrEP using  a 
questionnaire specifically designed for the SwissPrEPared program. 
2.1 Hypothesis and primary objectives 
The “SwissPrEPared Study” is based on the following hypotheses: 
1.
We expect a considerable number of individuals in Switzerland to be interested in starting 
PrEP. For those already taking PrEP, we assume there is a need for proper medical 
counselling and follow-up.
2.
We expect that a large nation-wide program providing regular counselling and follow-up will 
improve the retention in care of individuals at high risk of HIV and other STIs. 
3.
We expect the SwissPrEPared program to lead to a better detection of new HIV cases in 
Switzerland through regular testing among a high-risk population. 
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4.
We assume that systematic STI screening and appropriate clinical management will result in 
a decline of STIs rates, since there is a high prevalence of STIs in the population asking for 
PrEP. 
5.
We expect individuals at high risk of HIV to have higher rates of psychiatric disorders 
(depression, substance abuse); we assume that the SwissPrEPared questionnaire will be 
able to detect cases and to improve clinical management (i.e. early referral to specialist, 
appropriate therapy). 
The primary objectives of the SwissPrEPared study are to:
1. Explore the extent of PrEP use in Switzerland, using the following endpoints:

Number of individuals asking for PrEP 

Proportion of individuals qualifying for PrEP according to current guidelines

Demographic characteristics of individuals asking for PrEP

PrEP regime used

Mode of drug supply (pharmacy versus online)

Adherence rates

Occurrence of side effects 
2. Assessing and monitoring the occurrence of STIs in this particular population:

Prevalence and incidence of HIV

Prevalence and incidence of other STIs (syphilis, HBV/HCV, gonorrhoea and chlamydia, 
and mycoplasma genitalium)
3. To assess  sexual health and sexual well-being in individuals  asking  for PrEP using  a 
questionnaire specifically designed for the SwissPrEPared program. The following aspects will 
be explored: 

Sexual behaviour 

Factors associated  with  increased  sexual  risk taking  (recreational drug  use, 
number of sex partners, condomless sex with occasional partners)

Presence of psychiatric disorders (depression, substance abuse)

Influence of geosocial networking apps on sexual well-being of individuals asking 
for PrEP
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2.2 Primary endpoints
Time  points  and  methods  of  measurement  for  endpoint  assessment  are  described  under 
section 3.3 "study procedures". The following variables will be collected:

Number of individuals asking for PrEP 

Proportion of individuals qualifying for PrEP according to current guidelines

PrEP regime used (daily, intermittent, on-demand)

Mode of drug supply (pharmacy versus online)

Adherence rates (to PrEP and to program follow-up)

Occurrence of side effects 

Prevalence and incidence of HIV

Prevalence and incidence of other STIs (syphilis, HBV/HCV, gonorrhoea, chlamydia, 
mycoplasma genitalium)

Using the SwissPrEPared questionnaire:
o
Demographic characteristics of individuals asking for PrEP 
o
Sexual behaviour 
o
Factors associated  with  increased  sexual  risk taking  (recreational drug  use, 
number of sex partners, condomless sex with occasional partners)
o
Presence of psychiatric disorders (depression, substance abuse)
o
Influence of geosocial networking apps on sexual well-being of individuals asking 
for PrEP
2.3 Project design 
Nested within the SwissPrEPared Program, the “SwissPrEPared Study” is a large, multicentric, 
nation-wide  cohort  study  that  aims  to  longitudinally  follow  individuals  asking  for  PrEP 
prescription over a period of 3 years. 
The SwissPrEPared program has been described elsewhere (see document “SwissPrEPared 
program description”). In brief, seven  large  centers (i.e. Swiss  HIV Cohort Study  (SHCS) 
centers: Basel, Berne, Geneva, Lausanne, Lugano, St. Gallen and Zurich), four smaller health 
care structures (Checkpoints  Bern, Geneva, Lausanne, and Zurich) and private facilities in 
Zurich  (Medical  center  Kalkbreite,  dermatological  center)  will  be  participating  to  the 
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SwissPrEPared program. The program will not be restricted to these centers, i.e. other centers 
may apply for participation after the start of the program. 
2
PROJECT POPULATION AND STUDY PROCEDURES
3.1 Project population, inclusion and exclusion criteria 
These aspects are detailed in the SwissPrEPared program description (section 3.1). In brief, all 
individuals aged 18 years asking for PrEP prescription at one of the participating centers will be 
asked to participate to the SwissPrEPared program (consecutive ongoing recruitment). Only 
HIV-negative individuals will be deemed eligible. Participants for whom PrEP is not indicated or 
individuals declining PrEP will still be offered to participate in the program (i.e. to receive regular 
counselling and undergo STIs monitoring). 
According to the European MSM Internet Survey 2010 (EMIS-CH), approximately 80’000 MSM 
between 15 and 65 are currently living in Switzerland.17 Defining a “high risk of HIV infection” as 
3 episodes of condomless anal intercourse in the last 12 months, we estimate 4’000 MSM to 
qualify for PrEP in Switzerland. Exact estimates of the full program population cannot be drawn 
up, since it remains unclear how many non-users (either not indicated or declining PrEP) might 
be willing to participate in the program.
3.2 Recruitment, screening and informed consent procedure
These  aspects  are  detailed  in  the  SwissPrEPared  program  description  (section  3.2).  To 
facilitate reading, a copy of this section is provided here:
The MSM community will be informed about the SwissPrEPared program by advertising in print 
and  online  magazines,  and  in  geosocial  networking  apps  like  Scruff®,  Grindr®  or 
Planetromeo®. Potential participants will also be identified at local participating centers by their 
physician during consultation for PrEP prescription. Although not restricted to MSM, we expect  
only a small number of non-MSM individuals to participate in this program.  
All individuals willing to participate in the program will be asked to provide consent regarding the 
use of their personal health-related data for research purposes (general consent allowing data 
collection for the SwissPrEPared Cohort Study). The rationale underlying general consent is  
that  the  SwissPrEPared  program  is  expected  to  generate  highly  relevant  data  regarding  
individuals  seeking  PrEP  in  Switzerland  and  has the  potential to  address  a considerable  
number of research questions. Participants will be informed orally and in writing by trained 
medical staff working at the participating centers. Participants will be free to withdraw their  
consent at any time during the program. Individuals unable to follow program procedures (e.g. 
language barriers, mental or psychiatric disorders) will not be considered eligible for health-
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related data collection. More importantly, written informed consent will not be considered as a  
prerequisite for program participation, i.e. those declining personal data use will still be welcome 
to participate in the SwissPrEPared program (i.e. will benefit from regular counselling and STIs  
monitoring). Refusal will be consigned in personal records and no further data collection will be 
undertaken. 
The enrolment procedure will be conducted as follows:

At  every  local  participating  center,  potential  study  participants  will  be  identified  by 
screening the PrEP consultation schedule

One  day  prior  to  PrEP  consultation,  local  study  staff  will  contact  potential  study  
candidates on the phone. They will:
o
Inform them about the SwissPrEPared Program
o
Inform them about the possibility to participate in the nested SwissPrEPared  
cohort study 

If the candidate expresses interest for the study, the local study staff will send her/him  
via email:
o
The SwissPrEPared participant information
o
A link giving him access to the SwissPrEPared Questionnaire (secured web-
portal)

The local study staff will also inform participants that:
o
The questionnaire needs to be completed before the appointment at the PrEP 
consultation
o
All questions he/she might have will be answered at the PrEP consultation

At PrEP consultation:
o
All remaining questions will be clarified
o
The  informed  consent  form  will  be  signed  by  the  participant  and  the  local  
investigator
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Inclusion criteria
Exclusion criteria
Participation in the 
SwissPrEPared program
Aged ≥18 years
HIV negative
Eligibility criteria - SwissPrEPared Study
Individuals unable to follow 
program procedures (e.g. 
language barriers, mental or 
psychiatric disorders) 


If the candidate is not interested to participate in the study, the study staff will ask if the  
candidate allows them nonetheless to document the reason for refusal and his/her PrEP  
status (i.e. currently taking PrEP: yes/no): 
o
If yes, an identification number will be generated and the reason for refusal +  
PrEP status documented
o
If not, an identification number will be generated and no data will be collected.  
The  identification  number  is  needed  for  an  accurate  enrolment  log  (e.g. 
whenever the participant reconsiders participating in the study at some point 
later, no new identification number will be generated).   
3.3 Study procedures
3.3.1 PrEP prescription: 
Guidelines on PrEP prescription are detailed in the SwissPrEPared program description and in 
the Appendix 1 of this document.
3.3.2 Monitoring adherence, drug-related side effects and STIs 
Regular follow-up visits (i.e. approximately every 3 months) to assess PrEP adherence and 
drug-related side effects (clinical assessment and labs, i.e. full blood count, liver tests (ALT), 
proteinuria, creatinine, and glomerular filtration rate) will be recommended. 
Additionally,  regular  HIV  and  other  STIs  screening  will  be  recommended  to  program 
participants, i.e. before starting PrEP and during follow-up (approximately every 3 months). 
A full description of study visits is provided in Appendix 2.
3.3.3 Individualized counselling and follow-up using the "SwissPrEPared questionnaire"
Counselling and follow-up will be standardized throughout centers using an online, web-based 
questionnaire  specifically  designed  for  the  SwissPrEPared  program  (see  SwissPrEPared 
program  description  section  3.3.3  and Appendix  3  at  the  end  of  this  document).  The 
SwissPrEPared questionnaire shares similarities with questionnaires used by the SHCS to 
facilitate future research projects (data linkage).
Figure 3 outlines the procedures performed in the SwissPrEPared program and nested cohort 
study.
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The following table illustrates the main differences between the procedures carried on in the 
SwissPrEPared program versus the SwissPrEPared study.
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SwissPrEPared 
Program
SwissPrEPared 
Study
Official platform for the surveillance and the exchange of experience 
related to PrEP consultation
✓
✗
Improving the quality of care of individuals asking for PrEP (i.e. PrEP 
counselling, STI screening)
✓
✗
Targeted prevention measures to individuals at higher risk of HIV infection 
✓
✓
Monitor the safety of PrEP use in uninfected individuals 
✓
✓
Assess the extent of PrEP use in Switzerland
✗
✓
Assess and monitor the occurrence of STIs 
✗
✓
Assess sexual health and sexual well-being
✗
✓
Counselling about PrEP, HIV- and STI-prevention/-transmission
✓
✗
Assess PrEP-indication, -contraindications, -regime
✓
✓
Identify potential side-effects of PrEP
✓
✓
Assess concomittant medication
✓
✓
Assess vaccination status
✓
✓
Identify acute HIV-infection symptoms
✓
✓
Screen for depression and substance abuse 
✓
✓
Provide recommendations on laboratory testings 
✓
✗
Monitor long-term safety of PrEP in HIV-negative individuals
✗
✓
Provide recommendations on HIV/STI screening
✓
✗
Assess STI-/HIV-incidence
✗
✓
Assess overall adherence to SwissPrEPared recommendations
✗
✓
Table illustrating the differences between the SwissPrEPared Program and the 
SwissPrEPared Study
Overall objectives 
PrEP consultation
Processes of care 
PrEP: pre-exposure prophylaxis; STI: sexually transmitted infection
Figure 3. SwissPrEPared Program and nested cohort study – Design
Nested cohort study: 
•
Enrolled in program
•
Aged ≥ 18 years
•
HIV negative
•
Able to provide consent
Nested cohort study: data sources
•
SwissPrEPared questionnaire
•
Results from labs/screenings
Informed consent
Recommended (see SwissPrEPared Guidelines) but not mandatory
* PrEP intake not mandatory for program/study participation
Plain boxes indicate processes related to the SwissPrEPared Program; dashed boxes indicate processes related to the nested SwissPrEPared cohort study.
ALT: alanine aminotransferase; FBC: full blood count; GFR: glomerular filtration rate; HIV: human immunodeficiency virus; PrEP: pre-exposure prophylaxis; 
STI: sexually transmitted disease

3.3.4 Expected biases:
Selection bias may arise in several ways:

Individuals interested in taking PrEP may seek counselling outside participating centers 
(e.g. general practitioner, hospital not participating to the SwissPrEPared program).
> Since PrEP prescription remains a relatively recent and rather specialized procedure, 
we expect consultations for PrEP prescription occurring outside the program to be rare. 
Additionally, the program will not be restricted to these centers, i.e. other centers may 
apply for participation after the start of the program. 

Vulnerable  populations  (low  income,  younger  age,  MSW,  substance  abuse)  may 
renounce to program participation  due to the comprehensive  costs related to drug 
purchase or regular HIV and STI screenings.
> Financial support to reduce program-related costs is currently being discussed with 
several stake-holders. 

Loss to follow-up or drop-outs have to be expected when enrolling a healthy population. 
> Measures designed to improve retention will be applied (regular reminders for follow-
up visits, participant feedback actively sought to improve program procedures).
3.4 Withdrawal and discontinuation
Participants will be free to withdraw their consent to data collection at any time during the 
SwissPrEPared program. Whenever this occurs,  the identification key will be destroyed and 
data will be fully de-identified.
Data from participants lost to follow-up, unable to further attend follow-up visits or deceased 
during program course are expected to be used for research purposes.    
3
STATISTICS AND METHODOLOGY
4.1. Statistical analysis plan
4.1.1 Primary analyses
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Since the aim of this cohort study is mainly descriptive (i.e. to obtain representative estimates 
from individuals asking for PrEP in Switzerland), a power analysis was deemed not relevant. 
> Descriptive statistics: continuous data following a normal distribution will be expressed as 
mean and SD, categorical data as number and proportion. Standard methods for longitudinal 
studies (i.e. survival methods) will be used to describe HIV and STI incidence. 
> Inferential statistics: regression analyses will be performed to explore the association between 
predefined risk factors (such as recreational drug use, number of sex partners, or condomless 
sex with occasional partners) and the occurrence of HIV/STI infection. Whenever the data 
allows it (i.e. appropriate control group size), we will compare the HIV/STI incidence and sexual 
behavioural factors between individuals on PrEP and those not taking PrEP. 
4.1.2 Interim analysis:
Since participation and retention rates remain a relevant issue in longitudinal studies, we will 
conduct an interim analysis after 6 months with the aim to assess the demand, acceptability and 
resources related to the conduct of the SwissPrEPared cohort study. More specifically, we are 
interested in: 

Recruitment rates: number of participants enrolled compared to total number of potential 
candidates (i.e. total number of individuals asking for PrEP prescription)

Acceptability of the SwissPrEPared questionnaire: behavioural (uptake, adherence and 
completion of questionnaire) and self-reported (questionnaire part C) assessment. 

Retention rates: number of participants loss to follow-up.   

Reasons for loss to follow-up: self-reported assessment (questionnaire, part B). 

Costs related to study conduct: estimation of time and resources needed to conduct the 
study over 6 months.
We will conduct quantitative (i.e. recruitment and retention rates, behavioural component of 
questionnaire  acceptability)  and  qualitative  (i.e.  self-reported  component  of  questionnaire 
acceptability, reasons for loss to follow-up) analyses. For qualitative data, content analysis will 
be  performed  using  a  conventional  approach  (identification  of  themes,  open  coding, 
combination/stratification).
4.2. Handling of missing data 
In the case of dropouts or incomplete dataset, we will collect information to determine the nature 
of missing data (data missing completely at random (MCAR), data missing at random (MAR) or 
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data missing not at random (MNAR)). In case of missing randomness we will use multiple 
imputations for analyses where complete data are needed. We will also perform a  complete 
case analysis (assuming that all data are MCAR or MAR) and compare findings from both 
methods. 
5
REGULATORY ASPECTS AND SAFETY
5.1 Local regulations / Declaration of Helsinki
This research project will be conducted in accordance with the protocol, the Declaration of 
Helsinki [3], the principles of Good Clinical Practice, the Human Research Act (HRA) and the 
Human Research Ordinance (HRO) [1] as well as other locally relevant regulations. The Project 
Leader acknowledges his responsibilities as both the Project Leader and the Sponsor.
5.2 Notification of safety and protective measures (HRO Art. 20)
The project leader is promptly notified (within 24 hours) if immediate safety and protective 
measures have to be taken during the conduct of the research project. The Ethics Committee 
will be notified via BASEC of these measures and of the circumstances necessitating them 
within 7 days.
5.3 Serious events (HRO Art. 21)
If a serious event occurs, the research project will be interrupted and the Ethics Committee 
notified on the circumstances via BASEC within 7 days according to HRO Art. 211.
5.4 Amendments
Substantial changes to the project set-up, the protocol and relevant project documents will be 
submitted  to  the  Ethics  Committee  for  approval  according  to  HRO  Art.  18  before 
implementation. Exceptions are measures that have to be taken immediately in order to protect 
the participants. 
5.5 End of project
Upon project termination, the Ethics Committee is notified within 90 days.
1 A serious event is defined as any adverse event where it cannot be excluded, that the event is attributable to the 
sampling of biological material or the collection of health-related personal data, and which:
a. requires inpatient treatment not envisaged in the protocol or extends a current hospital stay;
b. results in permanent or significant incapacity or disability; or
c. is life-threatening or results in death.
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All  biological  materials  collected  during  the  SwissPrEPared  Program  will  be  processed 
according to protocols of local laboratories participating in the program (standard procedure not 
related to the conduct of the study). Health-related data collected during the SwissPrEPared 
Program and further used for study purposes will be anonymized upon termination of data 
analysis.
5.6 Insurance
Non-clinical/non-interventional research projects belonging to category A do not require an 
insurance.
 
6
FURTHER ASPECTS
6.1 Overall ethical considerations
The “SwissPrEPared Study” has been deemed “category A” research project according to art.7 
(HRO), as data collection only entails minimal risks and burden (i.e. health-related data routinely 
collected in the setting of a large prevention program). Whilst we recognise that sexual health 
research may raise some ethical concerns, we believe that the 4 ethical principles are well 
embedded in our project:

Autonomy: 
The following measures ensuring self-determination will be taken: informed consent will 
be sought orally and in writing by trained study staff; study information will be provided in 
an understandable language; participants will be free to withdraw their participation at 
any time during the study; individuals unable to follow or understand study procedures 
will  be excluded; subgroups in which the administration of TDF/FTC has not been 
studied extensively (such as individuals aged <18 years) will not be considered eligible; 
and finally, potentially eligible individuals will not be offered personal benefits for study 
participation (such as financial support for PrEP medication).

Beneficence: 
Risks and burden are deemed minimal: study participants will be expected to complete a 
self-administered questionnaire (SwissPrEPared questionnaire) at each visit, but full 
completion will not be mandatory for study participation. 
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Benefits: compared to non-participants, those taking part to the study will benefit from 
regular follow-up, screening for STIs and medical counselling. In the case of a positive 
STI diagnosis, state-of-the-art management will be proposed. 

Non-maleficence: 
Because research related to the SwissPrEPared program targets individuals engaged in 
high-risk behaviour and because of the highly sensitive nature of the data collected, 
several measures will be taken to ensure confidentiality, such as: a self-administered 
questionnaire,  data  collection  in  a  secured  database,  data  deidentification,  and 
publication of findings as aggregated data. 

Justice: the main  goal of this study is  to yield  more efficient  and  better targeted 
prevention  measures  for  individuals  at  high  risk  of  HIV  infection.  In  this  respect, 
participants will be the direct beneficiaries of the study findings, either during the study 
itself (through regular follow-up, screening for STIs and medical counselling) or in the 
near future. 
7
QUALITY CONTROL AND DATA PROTECTION
7.1 Quality measures 
Data generated by the SwissPrEPared program will be collected using an electronic Case 
Report Form (eCRF), i.e. the SwissPrEPared questionnaire. Quality checks will be performed 
already on entry, and by the coordinating study center (Zurich).  
For quality assurance the Ethics Committee may visit the research sites. Direct access to the 
source data and all project related files and documents must be granted on such occasions.
7.2 Data recording and source data
Data generated by the SwissPrEPared program will be collected using an eCRF providing 
custom access for each participant and researcher, based on a web application written in 
Python and a PostgreSQL database. The eCRF is based on the already-existing data collection 
web application of the SHCS. This eCRF does comply with the latest data safety requirements 
(e.g. audit trail, encryption of data at rest and in flight). Data sources will consist of routinely 
collected data from the SwissPrEPared program, i.e. original records (clinical assessment or 
labs) either in a paper or electronic version (depending on the system used by participating 
centers).  Data  will  then  be  entered  by  the  participants  themselves  and  by  health  care 
professionals participating in the SwissPrEPared Program. 
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7.3 Confidentiality and coding
Health-related data collected during the SwissPrEPared Program and further used for research 
purposes will be handled with utmost discretion and is only accessible to researchers who 
require the data to fulfil their duties within the scope of the research project (need-to-know 
basis). On the SwissPrEPared questionnaire and other project-specific documents, participants 
are only identified by a unique participant number. This number will be generated by the eCRF 
upon enrolment in the program. All personal data will be deidentified during data collection. The 
participant identification list will be stored in a password-secured database generated by local 
participating centers.  
Biological material (e.g. blood sample for HIV testing) collected during the course of the 
SwissPrEPared program will be handled following procedures specific to each participating 
center and their laboratories (standards of care). No biological material will be stored for study 
purposes (no use of Biobank).
7.4 Retention and destruction of study data and biological material
Health-related data collected from the SwissPrEPared program for research purposes will be 
stored 10 years after research findings publication. No biological material will be stored for study 
purposes (no use of Biobank).
8 
FUNDING / PUBLICATION / DECLARATION OF INTEREST
So far funding for the SwissPrEPared program and related research has been obtained from the 
following sources:
o
Swiss HIV Cohort Study
o
Federal Office of Public Health 
The funding organisations play no role in the design and conduct of the study; in the collection, 
management, analysis or interpretation of the data; or later in the preparation, review, or 
approval of the scientific manuscript.
The SwissPrEPared Research Team has no conflict of interest to declare.
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9
REFERENCES
1.
Gesundheit Bf. HIV, Syphilis, Gonorrhoe und Chlamydiose in der Schweiz im Jahr 2016: 
eine epidemiologische Übersicht. BAG-Bulletin 2017; 43: 29.
2.
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV 
prevention in men who have sex with men. N Engl J Med 2010; 363(27): 2587-99.
3.
McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the 
acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a 
pragmatic open-label randomised trial. Lancet 2016; 387(10013): 53-60.
4.
Molina JM, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at 
High Risk for HIV-1 Infection. N Engl J Med 2015; 373(23): 2237-46.
5.
Garcia B, Aragon T, Scheer S, HIV Epidemiology Section. HIV Epidemiology Annual 
Report 2015, San Francisco: San Francisco Department of Public Health. 2016.
6.
Nwokolo N, Hill A, McOwan A, Pozniak A. Rapidly declining HIV infection in MSM in 
central London. Lancet HIV 2017; 4(11): e482-e3.
7.
Grulich A, Guy R, Amin J, et al. Rapid reduction in HIV diagnoses after targeted PrEP 
implementation in NSW, Australia.  .  Conference on Retroviruses and Opportunistic Infections 
Seattle, Washington; 2018.
8.
Hampel B, Kusejko K, Braun DL, Harrison-Quintana J, Kouyos R, Fehr J. Assessing the 
need for a pre-exposure prophylaxis programme using the social media app Grindr(R). HIV Med 
2017; 18(10): 772-6.
9.
Afassinou K, Chirove F, Govinder KS. Pre-exposure prophylaxis and antiretroviral 
treatment interventions with drug resistance. Math Biosci 2017; 285: 92-101.
10.
Kouyos RD, Hasse B, Calmy A, et al. Increases in Condomless Sex in the Swiss HIV 
Cohort Study. Open Forum Infect Dis 2015; 2(2): ofv077.
11.
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 
2015. . Atlanta: U.S. Department of Health and Human Services; 2016.
12.
Shilaih M, Marzel A, Braun DL, et al. Factors associated with syphilis incidence in the 
HIV-infected in the era of highly active antiretrovirals. Medicine (Baltimore) 2017; 96(2): e5849.
13.
Alaei K, Paynter CA, Juan SC, Alaei A. Using preexposure prophylaxis, losing condoms? 
Preexposure prophylaxis promotion may undermine safe sex. AIDS 2016; 30(18): 2753-6.
14.
Newcomb ME, Mongrella MC, Weis B, McMillen SJ, Mustanski B. Partner Disclosure of 
PrEP Use and Undetectable Viral Load on Geosocial Networking Apps: Frequency of 
Disclosure and Decisions About Condomless Sex. J Acquir Immune Defic Syndr 2016; 71(2): 
200-6.
15.
Jenness SM, Weiss KM, Goodreau SM, et al. Incidence of Gonorrhea and Chlamydia 
Following Human Immunodeficiency Virus Preexposure Prophylaxis Among Men Who Have 
Sex With Men: A Modeling Study. Clinical Infectious Diseases 2017; 65(5): 712-8.
16.
Marcus JL, Levine K, Grasso C, et al. HIV Preexposure Prophylaxis as a Gateway to 
Primary Care. Am J Public Health 2018; 108(10): 1418-20.
17.
Marcus U, Hickson F, Weatherburn P, Schmidt AJ, Network E. Estimating the size of the 
MSM populations for 38 European countries by calculating the survey-surveillance 
discrepancies (SSD) between self-reported new HIV diagnoses from the European MSM 
internet survey (EMIS) and surveillance-reported HIV diagnoses among MSM in 2009. BMC 
Public Health 2013; 13: 919.
18.
Bundesamt für Gesundheit. Empfehlungen der Eidgenössischen Kommission für 
sexuelle Gesundheit (EKSG) zur HIV-Prä-Expositionsprophylaxe (PrEP) in der Schweiz. BAG-
Bulletin 2016; 4(January).
19.
Gunthard HF, Saag MS, Benson CA, et al. Antiretroviral Drugs for Treatment and 
Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral 
Society-USA Panel. JAMA 2016; 316(2): 191-210.
20.
European AIDS Clinical Society. Guidelines, Version 9.0, 2017.
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10 APPENDIX
Appendix  1:  Recommendations  regarding  PrEP  use  –  The  “SwissPrEPared 
guidelines”
These  recommendations  were  developed  to  help  the  PrEP-prescribing  health  care 
professionals participating to the SwissPrEPared program. They will be adapted at least once a 
year  based  on  growing  scientific  knowledge  and  on  quality  assessment  from  the 
SwissPrEPared Program. The study physicians are not bound to these recommendations, but 
will be asked in collegial discussions for their reasons if not. The following recommendations are 
in  line  with  the  current  recommendations  by  the  Federal  Commission  for  Sexual  Health 
(FCSH),18 the International Antiviral Society (IAS),19 and the European AIDS Clinical Society 
(EACS).20 
A1.1. Who to prescribe PrEP
The final decision to take PrEP is always made by program participants. PrEP is recommended 
for populations whose annual HIV incidence is at least 2% (evidence rating AIII). In Switzerland 
this is mainly the case for some subgroups of the MSM population. However, individual risk 
might be contextual: for instance, individuals not considered at risk in Switzerland may have a 
higher risk when travelling abroad; alternatively, behavior may change over time and those not 
benefitting from PrEP at first may benefit later in the future. Using PrEP as an HIV prophylaxis is 
a personal and highly individual decision. Health care professionals are not supposed to make 
this decision for participants, rather they should provide them with the best information and 
guide them in the decision-making process. Health care professionals should also rule out 
contraindications for PrEP and assess the existence of other medical conditions (such as 
anxiety disorders), since this could affect the decision-making process. Individuals who might 
benefit from PrEP, individuals who do not need PrEP and contraindications for PrEP are listed 
in Table 1. 
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Group with high prevalence of HIV (mainly: MSM) 
AND:
• anal sex (receptive or insertive) with inconsistent use of condoms or aim to have 
condomless sex in the future
• any recently reported STI 
• use of drugs in combination with sex, including alcohol
• repeated prescription of post exposure prophylaxis
HIV negative MSM in monogamous HIV serodiscordant relationship, if HIV+ partner 
under antiretroviral therapy with undetectable viral load for at least six months 
Monogamous relationship with partner recently tested HIV-negative
Acute or chronic HIV infection
Presence of significant proteinuria 
Kidney function with a clearance of less than 50 mL/min (Cockcroft formula)
History of chronic kidney disease
Table 1: Indications and contraindications for PrEP                                                                                                  
Individuals who may 
benefit from PrEP
Individuals who do not 
need PrEP
Contraindications         
for PrEP

> Other individuals at risk: 
Although PrEP is in Switzerland mainly indicated for subgroups of MSM, other individuals may 
also be at risk of HIV infection: heterosexuals frequently having unprotected vaginal or anal sex 
(specifically when abroad, i.e. sex-tourism), intravenous drug users or transgender individuals 
may also benefit from PrEP. It is worth to note, though, that daily dosing is the only regime 
recommended for women and transgender people, since levels of tenofovir have been found 10 
times lower in vaginal tissue than in rectal tissue and clearance is faster. 
A1.2 Medication
So far, the combination of 300mg TDF and 200mg FTC is the only recommended drug that 
should be used as PrEP. TDF/lamivudine, Tenofovir alafenamide /FTC, and TDF alone are not 
recommended for PrEP (evidence rating BIII).
Of note, in certain countries TDF is labelled as 245 mg rather than 300 mg to reflect the amount 
of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate). 
Studies with other drugs are ongoing and might lead to more possibilities in the future.
 
A1.3. Mode of PrEP
We currently recommend two regimes, which are well-studied and showed high efficacy in large 
clinical trials. The daily PrEP (= intake of 1 pill FTC/TDF every day) and the on-demand PrEP 
(according to the IPERGAY (Intervention Préventive de l’Exposition aux Risques avec et pour 
les Gays) protocol).4 Daily PrEP taken for a limited time-period (e.g. holidays) with long phases 
without PrEP intake is described as “holiday-PrEP” or "intermittent PrEP". The advantages, 
disadvantages and target population groups are listed in Table 2. Other regimes, such as 
continuous PrEP for four days a week, are not recommended until further evidence is made 
available (studies still on-going). 
> Daily regime:

Daily TDF/emtricitabine is the recommended regimen for men, women (evidence rating 
AIa), transgender individuals (evidence rating AIIa) at risk of sexual exposure (evidence 
rating AIa) and for individuals injecting drugs (evidence rating BIa).

A 1-week lead-in time is recommended with daily dosing for rectal, penile, and vaginal 
exposures with daily TDF/emtricitabine to ensure that adequate tissue levels are 
achieved (evidence rating CIII).
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
If PrEP is to be discontinued, TDF/emtricitabine should be stopped 1 week after the last 
sexual exposure at the earliest (evidence rating CIII).
> On-demand regime:
On-demand TDF/emtricitabine PrEP, also known as “2-1-1” dosing may be considered as an 
alternative to daily PrEP for MSM with infrequent sexual exposures (evidence rating AIa). 
The IPERGAY study assessed on-demand PrEP with TDF/emtricitabine given as 2 doses 2 to 
24 hours before sex, 1 dose 24 hours after the first (double) dose, and 1 dose 24 hours later 
(“2-1-1” dosing). For consecutive sexual contacts, men were instructed to take 1 pill per day 
until 2 days after the last sexual encounter. With each new sexual encounter, PrEP was to be 
initiated with a double dose, unless the last PrEP dose had occurred within 7 days, in which 
case only 1 preexposure dose was recommended. 

This regimen is not recommended in other risk groups than MSM, especially not in 
women, since tenofovir levels were found 10-times lower in vaginal tissue than in rectal 
tissue and since clearance is faster.

This regime is not recommended in patients with active HBV infection because of the 
risk of hepatitis flare and hepatic decompensation (evidence rating BIIa).

If intercourse is planned in the context of 2-1-1 PrEP regimen, the first (double) dose of 
TDF/emtricitabine should be taken closer to the 24-hour precoital time than the 2-hour 
time (evidence rating CIII).
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Table 2: Advantages and disadvantages of different PrEP regimes and possible populations.
Daily PrEP
Intermittent PrEP
On-demand PrEP
Advantages

Best evidence

Good protection, 
even when 
adherence is not 
optimal 

Less long-term side 
effects than daily 
regime

Probably better 
protection than on-
demand-regime in 
people with drug-
adherence problems.

Less long-term 
side effects

Lower costs
Dis- 
advantages

Highest risk for 
long-term side-
effects

Costs

No evidence from 
clinical studies

No protection during 
PrEP-free periods, 
but possible change 
in risk-behavior due 
to “PrEP-
experience”.

Less evidence 
than the daily 
regime

No protection 
during PrEP-free 
periods, but 
possible change 
in risk-behavior 
due to “PrEP-
experience”
People that 
might benefit 
from this 
regime

Individuals having 
frequent sexual 
exposure (more 
than once a 
month)

Individuals having 
spontaneous 
sexual contacts

Individuals who 
might have 
problems with 
drug-adherence

Women or 
individuals born 
female

Individuals having a 
higher risk of HIV 
during specific times 
periods. 

Individuals having 
only infrequent 
sexual exposure 

Individuals having 
planed sex (not 
spontaneous)
Not 
recommended 
for

Individuals having 
general 
contradictions for 
PrEP

Individuals having 
general 
contradictions for 
PrEP

Individuals having 
spontaneous sexual 
contacts

Women or 
individuals born 
female 

Individuals having 
spontaneous 
sexual contacts

Individuals who 
might have 
problems with 
drug-adherence
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Appendix 2: SwissPrEPared program – Recommended visits 
Individuals asking for PrEP will first be assessed at baseline visit (see description below). For 
those deciding to start PrEP, a second visit is recommended 4 weeks after PrEP initiation to 
evaluate early side-effects and to rule out an acute HIV-infection missed out at baseline visit 
(HIV test window period). After that second visit, a 3-monthly plan is recommended for all 
participants using PrEP, and a 6 to 12-monthly plan for participants at risk of HIV who decided 
not to start PrEP.
Each PrEP prescription should be for a period of maximum 3 months (90 tablets) to ensure 
appropriate monitoring. 
A2.1 General recommendations for every visit:
Besides the recommended laboratory- tests, each visit should be used to: 

Evaluate the knowledge of the participant about PrEP, HIV and STIs transmission

Remind the participant that condoms are required to prevent acquisition of non-HIV 
STIs, especially hepatitis C. 

Inform participants that PrEP does not protect 100% against HIV, and that regular HIV 
testing (every 3 months) is necessary to prevent resistance in the case of undiagnosed 
HIV. 

Screen participants for depression and substance abuse 

Evaluate counselling adherence 

Assess potential side effects related to TDF/FTC

Assess if participants expectations regarding counselling are met
A2.2 Baseline visit 
The following should be performed at baseline visit:

Assessing the indication for PrEP, ruling out contraindications (i.e. medical history, 
current medication (especially nephrotoxic drugs), osteoporosis, kidney and liver 
diseases, previous STIs, previous post-exposure prophylaxis (PEP), symptoms or signs 
consistent with an acute HIV-infection within the last six weeks, sexual behaviour, drug 
use in combination with sex).

The advantages and disadvantages of the different PrEP regimes should be discussed 
with each person.  

Assessment of serum creatinine level,  alanin-aminotransferase (ALT, GPT) and full 
blood count 
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
HIV screening using 4th generation HIV-Combo test to avoid resistance in the case of an 
undiagnosed HIV infection. People who experienced high risk situations in the 6 weeks 
prior to starting PrEP should either have an additional HIV-PCR test or should be tested 
again using a 4th generation HIV-Combo test 4 weeks after starting PrEP (i.e. at safety 
visit). 

Hepatitis B status should be evaluated before starting PrEP but should not delay PrEP 
initiation. HBs-Antibody negative individuals should be recommended a full course of 3 
Hepatitis B vaccinations and a vaccination titer control one month after the third vaccine. 
People with an incomplete vaccination status (HBs-antibody less than 100 but more than 
10) should be recommended a single Hepatitis B Booster vaccination with a vaccination 
titer control 4 weeks after. For individuals with active HBV infection (detectable HBsAg), 
discontinuation  of  TDF/FTC  PrEP  could  lead  to  acute  HBV  flares  or  hepatic 
decompensation, particularly for patients with hepatic cirrhosis; careful monitoring of 
HBV  infection  and liver function is recommended after discontinuation  of TDF/FTC 
(evidence rating AIIa). On-demand PrEP is not recommended for individuals with an 
active Hepatitis B infection.

Assessment of Hepatitis A-vaccination status.

Individuals asking for PrEP should be screened for other STIs, even when they decide 
not to take PrEP or show no symptoms. Syphilis should be screened using serological 
tests (TPHA, RPR), Hepatitis C should be tested using serological tests or blood PCR, 
and pooled PCR from rectum, pharynx and urethra should be performed for chlamydia 
and gonorrhoea. Individuals with symptoms of urethritis, proctitis or pharyngitis should 
be also screened for mycoplasma genitalium. 

HPV vaccination should be discussed with every participants, especially, those aged 26 
years or younger.
In case of a contraindication for PrEP, the participant should be rescheduled within 7 days. If a 
participant is already taking PrEP at baseline, the interventions will be adapted accordingly. If a 
participant qualifies for PrEP but decline starting PrEP, a follow up every 6 to 12 months is 
recommended to perform STI and HIV testing. 
A2.3. Safety-visit, 4 weeks after PrEP start 
The following should be performed at safety-visit:

Assessment of side effects

Re-assessment of PrEP indication and PrEP-regime 

Assessment of PrEP adherence
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
HIV 4th generation test 

Assessment of new medication (especially nephrotoxic drugs), 

Measurements of serum creatinine level, ALT, GPT and full blood count
A2.4 Follow-up visits, 3 months after safety-visit and then every 3 months

Re-assessment of PrEP indication and PrEP-regime. 

HIV 4th generation test. 

STI tests (Syphilis, Gonorrhea, Chlamydia) are usually recommended every 3 months but 
the frequency should be adapted, if the participant had no or very few sexual intercourses 
since the last visit 

Assessment of sexual risk behaviour (for instance drug use in combination with sex) 

Assessment of creatinine, glomerular filtration rate and proteinuria (urine dipstick), ALT, full 
blood count 

Every 6 months:  anti-HCV-Ig.
Table 3: Appointment schedule and key clinical assessments
Baseline 
visit
Safety 
visit
Follow-up visit 
(every 3 months)
PrEP counselling which includes: 

medical history and clinical examination

information on PrEP

conception/ pregnancy 

short and long-term side effects 

risk of developing resistance in the case of 
undiagnosed HIV 
x
(Re-)Assessment of PrEP indication, regime and 
adherence 
x
x
x
Assessment of side effects, including interaction 
with existing medications or supplements
x
x
x
Behavioral risk assessment 
x
x
Symptoms of acute HIV infection (<1 month) 
x
x
x
Adherence to counselling
x
x
x
Participant’s feedback on counselling 
x
x
x
HIV test 
x
x
x
STI screening (Syphilis, Gonorrhea, Chlamydia)
x
x
x
Hepatitis C serology
x
Every 6 months or if 
clinically indicated
Hepatitis B Serology
x
Assessment of vaccination status
x
Labs: serum creatinine level, ALT, GPT, full blood 
count
x
x
x
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Appendix 3: SwissPrEPared Questionnaire
Part A: baseline visit
1.
Year of birth
2.
Postal-code (first two characters)
3.
What is your current gender identity
1= male,2= female, 3= transgender; 
9= I do not categorize myself
4.
What sex were you assigned at birth
1= male,2=female,3=intersex, 9=not 
stated
5.
Which of the following options best describes 
how you think of yourself
1= homosexual,2= heterosexual, 3= 
bisexual; 5= I don`t usually use a 
term
6.
Do you consider yourself a member of an 
ethnic or racial minority in Switzerland?
Yes/No; if Yes free text
7.
Which country were you born in?
List, if not Switzerland
7a
(If 7= any other country than Switzerland), 
Since when do you live in Switzerland?
1= Since always; 2= Less than 12 
months; 3= 1-5 years; 4= 5-10 
years; 5=More than 10 years
8.
What level of education did you reach?
1=no completed school or 
professional education; 
2=mandatory school (9 years in 
Switzerland); 3=finished 
apprenticeship; 4=bachelor; 
5=higher professional education; 
6=higher technical or commercial 
school;7=university; 9=no 
information; 0=other
9.
Which of the phrases would you say comes 
closest in your feelings about your income 
these days:
1= Living really comfortable on 
present income; 2= living 
comfortable on present income; 3= 
Neither comfortable nor struggling 
on present income; 4 = Struggling 
on present income; 5= Really 
struggling on present income
10
.
Do you take any other medication (other than 
PrEP) at the moment
Free text
11
.
Do members of your close family (parents, 
grandparents) suffer from osteoporosis (bone 
disease)?
1=Yes
2= No
12
.
Have you ever taken PrEP?
1= Yes
2= No
13
.
If 12=yes, when have you started?
(Month/Year)
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14
.
Have you ever used post exposure prophylaxis 
(PEP)?
Yes/No
15
.
Have you ever been diagnosed with an STI?
If Yes, 1=Syphilis;, 2= Gonorrhea; 
3= Chlamydia; 4=Hepatitis A; 5= 
Hepatitis B; 6= Hepatitis C; 7= 
Mycoplasma genitalium, 8= genital 
Herpes; 9= others (free text)
16
.
When was your last HIV test?
dd/mm/yy
17
.
When was your last anal or vaginal sex where 
you did not use a condom?
1= Last 48 hours
2= 3-15 days 
3= 15 – 42 days 
4= 42 – 90 days
5=  More than 90 days.
18
.
Referring to your last condomless anal or 
vaginal sex: Did you know the HIV status of 
the partner?
1= unknown; 2=HIV positive, 
unknown if under antiretroviral 
treatment (ART); 3=HIV positive, 
under ART; 4=HIV positive not 
under ART; 5=HIV negative 
19
.
Would you prefer another form of PrEP than 
the daily intake of a tablet, if it were available?
1= no
2= yes, a monthly injection
2 = yes, a 2-monthly injection
3= yes, a 3-monthly injection
4= yes, an implant
4 = other free text
Part B1: baseline and follow-up visit 
This questionnaire will be sent to the program participant (text message or email) together with 
a reminder for the next appointment. Part A, questions 1 to 11, will be displayed as well and the 
participant will be asked to assess if the information is still valid or if changes need to be made.
#
Q
A
1.
Do you already have a 
new appointment?
1=yes;2=no
2.
If 1= no, Do you want to 
schedule a new 
appointment?
1= yes (please contact your health care provider after 
this survey)
2= no, because I do not have time at the moment, but I 
want to continue with the program
3= no, I want to stop the program because I stopped 
PrEP
4= no, I want to stop the program, but I continue with 
PrEP
3.
If 2=2 when shall we 
remind you for a new 
appointment
1= in 1 Week; 2 in 2 weeks; 3= in 1 months; 4=in 3 
months
4.
If 2=4 please tell us why 
you want to stop the 
Free text
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program.
5.
Are you taking PrEP at 
the moment
1=yes;2=no
6.
If 5=1: Which mode do 
you use PrEP at the 
moment ?
1=daily (every day, including today)
2=daily, but only for certain periods
3=before and after planned sex, but not on a daily basis 
(2 pills 2-24 hours before planned sexual activity as well 
as one pill 24 hours and 48 hours after planned sexual 
activity)
 4= I use a different regime than the described ones: 
please specify: free text
7.
If 6=2 how many days 
before a sexual risk 
situation do you usually 
start PrEP?
1-30
8.
If 6=2 how many days 
after your last sexual risk 
do you usually take 
PrEP?
1-30
9.
Do you think you can tell 
when you missed a 
dose?
1=Yes, I can always tell; 2=Not sure I can tell; 3=No, I 
can’t tell
10.
If 6=2 or 3: how many 
days have you been on 
PrEP during the last 90 
days
1-90 (estimated)
11a.
If 6=2 or 3 How often did 
you miss a dose in the 
last 3 months?
1= never; 2= once or twice; 3=3-5; 4=6-10 4=more than 
10
11b.
If 6=1 How often did you 
miss a dose in the last 3 
months? (Assuming 1 pill 
a day if taken daily)
1=never; 2=more than once a week, 3=once a week, 
4=once every second week,5= once a month, 
12.
If 6= 1 Did you miss 
more than one dose in a 
row?
1=yes, (how many days) 2=No
13.
Where did you purchase 
your PrEP
1= online pharmacy (outside Europe); 2=online 
pharmacy (Europe); 3= in a regular pharmacy outside 
Switzerland; 4= in a pharmacy in Switzerland; 5= got it 
from someone I know; 6=other
14.
Did you experience any 
side effects or other 
health problem?
1=no; 2=yes, I experienced stomach/digestive 
problems, 3=yes, I experienced headaches, 4=yes, I 
experienced other problems: (free text)
15.
Are you in a relationship 
with a steady partner at 
the moment?
1=yes, 2=No;3= I am not sure/ it is not defined
16.
If 15=1, do you know 
your HIV status of your 
partner
1= no; 2=HIV positive, I don`t know if he/she is under 
antiretroviral therapy (ART); 3=HIV positive, he/she is 
under ART; 4=HIV positive, he/she is not under ART; 
5=HIV negative
17.
(Not asked if 15=2) With 
your steady partner, do 
you use condoms for 
1=always;2=mostly;3=sometimes;4=never
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anal or vaginal sex?
18.
How many sexual 
partners have you had 
since your last visit?
Absolut number (estimated)
19.
In the last 3 months, how 
often have you used 
condoms with occasional 
partners for anal or 
vaginal sex?
1=always;2=mostly;3=sometimes;4=never;5=no anal or 
vaginal sex with occasional partners in the last three 
months
20.
Do you currently have 
any of these symptoms?
1=genital discharge; 2= pain or burning when urinating; 
3= pain or swelling of the testicles; 4= genital ulcer, 
vesicles, rash, or swelling; 5= abdominal pain; 6= pain 
at defecation; 7= rectal pain or discharge; 8= rectal 
ulcer, vesicles, rash or swelling; 9=sore throat;
21.
How happy are you with 
your sexual life at the 
moment
Scale 1 to 10, where 1 = very dissatisfied; 10 is very 
happy. 
Over the last 2 weeks, 
how often have you been 
bothered by the following 
problems: 
22.
Feeling nervous anxious 
or on the edge
1= not at all; 2= some days; 3= more than half the days; 
4= nearly every day
23.
Not being able to stop or 
control worrying
1= not at all; 2= some days; 3= more than half the days; 
4= nearly every day
24.
Little interest or pleasure 
in doing things
1= not at all; 2= some days; 3= more than half the days; 
4= nearly every day
25.
Feeling down, 
depressed, or hopeless
1= not at all; 2= some days; 3= more than half the days; 
4= nearly every day
26.
Have you used any of 
the following substances 
in the last three months?
1= Alcohol; 2= poppers (nitrite inhalants); 3= Sedative 
or tranquilizers (Valium®, Rivotril®, Rohypnol®, 
Xanax®, Seduxen®, Phenazepam); 4=Cannabis; 
5=Ecstasy/MDMA; 6=Cocaine; 7= Crack cocaine; 
8=GHB/GBL; 9=Ketamine; 10= Amphetamine/Speed; 
11=Mephedrone; 12= Synthetic stimulants other than 
mephedrone (eg. MXE, bathsalts, 3MMC, 4MEC,4_FA, 
XTClight); 13 =Crystal Meth/Tina,14= Heroin or other 
opioids, 15= LSD (acid), 16= I took drugs, but I don`t 
know which drugs , 17= I have not taken any drugs or 
alcohol
27a.
If 27 is any other than 
17: Have you used any 
1= Alcohol; 2= poppers (nitrite inhalants); 3= Sedative 
or tranquilizers tranquilizers (Valium®, Rivotril®, 
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of these substances in 
combination with sex in 
the last three months?
Rohypnol®, Xanax®, Seduxen®, Phenazepam); 
4=Cannabis; 5=Ecstasy/MDMA; 6=Cocaine; 7= Crack 
cocaine; 8=GHB/GBL; 9=Ketamine; 10= Amphetamine/
Speed; 11=Mephedrone; 12= Synthetic stimulants other 
than mephedrone (eg. MXE, bathsalts, 3MMC, 
4MEC,4_FA, XTClight); 13 =Crystal Meth/Tina,14= 
Heroin or other opioids, 15= LSD (acid), 16= I took 
drugs, but I don`t know which drugs; 17= I have not 
taken any drugs or alcohol in combination with sex
27b.
If 27 was 6, 9. 10, 13 or 
14: Have you injected 
any of these 
substances? 
1=Cocaine, 2=Ketamine, 3=Amphetamine, 4=Crystal 
meth, 5=No intravenous use
28.
Do you worry about your 
recreational substance 
use? (for example: did 
you encounter problems 
in your social life, at work 
or with your health due to 
these substances?)
1=yes; 2=no
29.
How many cigarettes do 
you smoke per day
0-99
30.
Since your last visit do 
you take any new 
medication?
“list of last visit should be shown”
31.
Do you want your doctor/
health care provider to 
see the answers of your 
questionnaire? It will help 
her/him to address 
specific topics, that might 
be important for you.
1= yes
2= no
31.
Is there something 
specific you want to 
discuss with your doctor 
on this visit?
Part B2 (optional): baseline and follow-up visit
After finishing Part B1, participants will be given the possibility to answer additional questions. 
Alternatively, they may exit the online questionnaire and proceed to the next follow-up visit.
 
1.
Since your last negative HIV 
test, did you think your pill 
intake was good enough to 
protect you from HIV when 
you were at risk?
1=yes, 2=No
2.
If 1=2, was this because you 1=I forgot to take pills; 2=I had an unexpected risk 
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(Please tick all that apply)
when not taking pills before; 3=I lost pills; 4=I did not 
have pills during a period of risk; 5=I ran out of pills; 
6=Other reasons (free text)
3.
If B1,15=1 and B1, 5=1: 
does your partner know that 
you take PrEP?
1=yes; 2=No
4.
If B1,15=1 How good can 
you talk with your partner 
about the sexual relationship 
you have with each other?
1-10, 999= We are not in a sexual relationship
5.
Did you engage in fisting in 
the last 3 months?
1=no; 2=yes active and passive; 3= yes only active; 
4=yes only passive
6.
Do you use dating-apps?
(planetromeo®, grindr®, 
Scruff®, hornet® etc.)
1=Yes; 2=No
7.
If 6=1 how often do you 
approximately switch on a 
dating app
1=several times a day; 2= once a day; 3=several 
times a week; 4= once a week; 5= every couple of 
weeks; 6= Less frequently 
8.
If B1,5=1 and 6=1, do you 
state on your dating-profile 
that you use PrEP?
1=yes, 2=No
9.
Does using a dating app 
improve your sex life?
1= yes, my sex life improved a lot, 2= yes, my sex life 
improved a bit; 3=My sex life hasn`t changed due to 
dating apps; 4=no, my sex life got a bit worse; 5=no, 
my sex life got much worse; 9= I don’t know/can’t tell
10.
If 8=1: Have people made 
abusive comments on 
dating apps regarding your 
PrEP use in the last three 
months?
1=yes, 2=No
11.
Have you been 
discriminated against on a 
dating app in the last three 
months
1= no; 2= yes because of my skin color, 3 = yes, 
because of my age; 4= Because of my body 
features. 
12.
In the last three months, 
have you used dating apps 
for sexdates only?
1=Yes; 2=No
12a.
If 12=2, for what else have 
you used them?
1=To meet someone, hoping that a relationship 
would develop; 2: To meet someone for social 
activities, without being on a date or having sex. 3= 
to chat only
13.
Have you felt ashamed of 
your behavior against 
others on a dating app in 
the last three months?
1=yes; 2=no
14.
Does the use of Dating 
Apps impair your other daily 
activities?
1=yes; 2=no
15.
Where have you received 
health/medical information 
in the last 3 months
1=physician/health care professional, 2=friends, 
3=internet (also in chat/dating apps)
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16.
If 15= 3: Which internet 
sources have you used
1= search engines (google, yahoo..), 2= social media 
(facebook) 3=Chatrooms (gayromeo, grindr) 
4=specific health pages, 5= original medical journals, 
6=forums
17.
If 16=4 or 5
Please specify
18.
Do you want your 
doctor/health care provider 
to see the answers of your 
questionnaire? It will help 
her/him to address specific 
topics, that might be 
important for you.
1= yes
2= no
Part C (Feedback): baseline and follow-up visit
1.
How satisfied have you been with your last 
visit?
1-10 (1=worst 10=best)
2.
Is there anything you want to tell us? 
Free text
Part D (to be completed by health care providers): baseline and follow-up visit
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1.
Reason for the visit today
1=information on PrEP;2=start PrEP; 
3=regular PrEP follow-up; 4=unplanned 
visit (STI); 5=unplanned visit (other) 
(please specify: free text)
2.
Does the patient qualify for PrEP 
according to the current 
SwissPrEPared recommendations?
1=No 2=Yes
3.
Side effects of PrEP
1= No, 2=Nausea; 3= 
Diarrhea;4=Headache, 5= other
4.
Has the patient reported symptoms of a 
primary HIV infection?
1=No; 2=Yes
5a.
Screening for Gonorrhea
1=positive 2=negative 3=not performed
5b.
Screening for Chlamydia
1=positive 2=negative 3=not performed
5c.
Screening for M. gen.
1=positive 2=negative 3=not performed
5d.
Screening for Syphilis
1=positive 2=negative 3=not performed
5e.
Screening for Hep C
1=positive 2=negative 3=not performed
6.
HIV test performed
1=No; 2=yes 4th generation Combotest; 
3=yes pcr; 4= yes, other than 4th 
generation or pcr; 
6a.
If 6=yes, result?
1=reactive 2=not reactive
6b.
If 6a=reactive, was an infection proven?
1=No 2=Yes
7.
If 5a-d=no, please explain why no STI-
screening was performed
Free text
8.
Creatinine/GFR
….Unit
9.
GPT
…Unit
10.
Prot/creat Quotient
…Unit
11.
Last HBV screening?
Date: XXX
11a.
Anti-Hbs ag
1=Neg 2=Pos, Titer if available (show last 
value)
11b.
Hbsag
1=Neg 2=Pos
11c.
If Hbsag=Pos HBV DNA PCR: 
XXX copies/ml
11d.
Anti-Hbc
1=Neg 2=Pos
12.
Medical history
Sub-questions
12a.
Depression
1=No 2=Yes
12b.
Renal disease
1=No 2=Yes
12c.
Osteoporosis
1=No 2=Yes
12d.
Other relevant
Free text
13.
Any Co-Medication
Show list, patient filled out
Free text
14.
Any new medical problems/diagnosis 
since last visit
Show list of diagnosis
Grouped by organ systems
15.
Vitamin D supplementation?
1=Yes; 2=No
16.
Vaccinations
Show list of vaccinations from last visits
1= Gardasil®9; 2=Engerix; 
3=Haverix;4=Twinrix;5=other (free text)
17.
Assessment of existing knowledge 
about PrEP done?
1=No; 2=Yes
18.
Information provided on Adherence 
issues, risk on resistance, STI including 
HCV and HIV, side-effects of 
TDF/FTC?
1=No; 2=Yes
19.
Information provided about signs and 
symptoms of an acute HIV infection
1=No; 2=Yes

Part E (to be completed by study participants): unplanned visit
1.
What was the reason for your visit today
1=sexual transmitted disease, 
2=PrEP related problem; 3=other 
acute illness
Continue with C
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