Evaluation of Implementation of Pre-exposure Prophylaxis (PrEP) in Subjects at Particular Risk of Infection With Human Immunodeficiency Virus (HIV).
Conditions: Hiv, Sexually Transmitted Diseases, Mental Health Wellness 1
Sponsor: Oslo University Hospital

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CLINICAL STUDY PROTOCOL 
 
Protocol no.:  SMR-3395 
 
 
 
Title:  
Evaluation of implementation of pre-exposure prophylaxis (PrEP) in subjects at particular risk 
of infection with human immunodeficiency virus (HIV).  
 
Indication:  
Pre-exposure prophylaxis (PrEP) for HIV 
 
Investigational medicinal product:  Emtricitabine/tenofovir disoproxil combination tablet (FTC/TDF) 
 
Principal Investigator: 
Anne Olaug Olsen, Oslo University Hospital, The Olafia Clinic Oslo, Norway 
  
 
Sponsor: 
Oslo University Hospital (OUH) 
 
 
Protocol date and version: 
Version 1.1, 30.01.2018 
 
  
 
 
CONFIDENTIALITY STATEMENT 
This material is confidential and the property of Sponsor. Its contents must not be disclosed or used 
except as authorised in writing by Sponsor. 
 

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Contact Information 
 
Sponsor 
Oslo University Hospital  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Site personnel 
OUH 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study sites 
 
 
 
Primary contact:  
Anne Olaug Olsen 
Oslo University Hospital 
National Advisory Unit for Sexually Transmitted Infections 
Olafiaklinikken 
Postbox 4763 
0506 Oslo, Norway 
 
Visiting address:  
Trondheimsveien 2, building N 
 
Phone: +47 2307 5864 
E-mail: anools@ous-hf.no 
 
 
 
Principle investigator Anne Olaug Olsen, Senior Consultant 
Physician and Ass. Professor 
 
Investigator and Senior Consultant Physician Frank Olav Pettersen 
Oslo University Hospital 
National Advisory Unit for Sexually Transmitted Infections and 
Head Center for Imported and Tropical Diseases 
Dept. of Infectious Diseases 
Postbox 4950 Nydalen 
0424 Oslo 
 
Visiting address: 
Kirkeveien 144, building 3 
Phone: +47 22119100 or 92095743 
E-mail: uxpfra@ous-hf.no 
 
 
 
Michelle Hanlon, Senior Consultant Physician, The Olafia 
Clinic, OUH, National Advisory Unit for Sexually Transmitted 
Infections 
 
Jorge Johansen, Specialist Nurse Practitioner, The Olafia 
Clinic, National Advisory Unit for Sexually Transmitted 
Infections OUH  
 
Anne Ma Dyrhol Riise, Head Research & Development and 
Professor Dept. of Infectious Disease, OUH 
 
Anne-Marte Bakken Kran, Senior Consultant and Ass. 
Professor, National Reference Laboratory for HIV, Dept. of 
Microbiology, OUH 
 
Linda Gail Scheie, Study Nurse, Dept. of Infectious Diseases, 
OUH 
 
 
 
Other national study centers will be invited to participate. 

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TABLE OF CONTENTS 
 
CONTACT INFORMATION ........................................................................................................2 
TABLE OF CONTENTS .............................................................................................................3 
PROTOCOL OUTLINE...............................................................................................................5 
LIST OF ABBREVIATIONS .......................................................................................................7 
1 
INTRODUCTION ................................................................................................................8 
1.1 
AIM OF PRESENT STUDY ...............................................................................................9 
2 
OBJECTIVES .................................................................................................................. 10 
3 
POPULATION ................................................................................................................. 10 
3.1 
INCLUSION CRITERIA .................................................................................................. 10 
3.2 
EXCLUSION CRITERIA ................................................................................................. 10 
3.3 
CONTROL GROUP ...................................................................................................... 11 
3.4 
RECRUITMENT AND SCREENING .................................................................................. 11 
3.5 
SUBJECT WITHDRAWAL .............................................................................................. 12 
4 
TREATMENT PROCEDURES ........................................................................................ 12 
4.1 
STUDY PLAN .............................................................................................................. 12 
4.2 
VARIABLES ................................................................................................................ 12 
4.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .................................................... 13 
4.3.1 
General ............................................................................................................ 13 
4.3.2 
Seriousness ..................................................................................................... 14 
4.3.3 
Severity ............................................................................................................ 14 
4.3.4 
Relationship to study medication ..................................................................... 14 
4.3.5 
Serious adverse reactions and unexpected adverse reactions ....................... 15 
4.3.6 
Reporting of suspected unexpected serious adverse reactions by Investigator
 
15 
5 
INVESTIGATIONAL MEDICINAL PRODUCT ................................................................ 15 
5.1 
INVESTIGATIONAL MEDICINAL PRODUCT AND COMPARATOR ......................................... 15 
5.2 
SUPPLY, PACKAGING, LABELLING, HANDLING AND STORAGE ........................................ 16 
5.3 
DOSAGE AND ADMINISTRATION ................................................................................... 16 
5.4 
DURATION OF TREATMENT .......................................................................................... 17 
5.5 
METHODS FOR ASSIGNING SUBJECTS TO TREATMENT ................................................. 17 
5.6 
CONCOMITANT MEDICATION ....................................................................................... 17 
5.7 
IMP ACCOUNTABILITY ................................................................................................ 17 
6 
VARIABLES .................................................................................................................... 17 
7 
STATISTICAL METHODOLOGY AND DATA MANAGEMENT .................................... 18 
7.1 
STATISTICAL ANALYSIS PLAN ...................................................................................... 18 
7.2 
STUDY POPULATIONS ................................................................................................. 18 
7.3 
DESCRIPTIVE STATISTICS ............................................................................................ 18 
7.4 
MISSING DATA ............................................................................................................ 18 
7.5 
DATA COLLECTION / CASE REPORT FORMS ................................................................. 18 
7.6 
DATA MANAGEMENT ................................................................................................... 18 
8 
REGULATORY AND ADMINISTRATIVE PROCEDURES ............................................ 19 
8.1 
INSTITUTIONAL REVIEW .............................................................................................. 19 
8.2 
PATIENT INFORMATION / INFORMED CONSENT ............................................................. 19 
8.3 
SUBJECT CONFIDENTIALITY ........................................................................................ 19 

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8.4 
SUBJECT TREATMENT PLAN ....................................................................................... 19 
8.5 
GCP ......................................................................................................................... 19 
8.6 
RECORD RETENTION .................................................................................................. 19 
8.7 
QUALITY ASSURANCE ................................................................................................. 20 
8.8 
INSURANCE AND LIABILITY .......................................................................................... 20 
8.9 
END OF TRIAL ............................................................................................................ 20 
8.10 
STUDY REPORT ......................................................................................................... 20 
8.11 
PUBLICATION AND DATA RIGHTS ................................................................................. 20 
9 
REFERENCES ................................................................................................................ 21 
10 
SIGNATURES ............................................................................................................. 22 
11 
SIGNATURE PAGE FOR INVESTIGATORS ............................................................. 23 
12 
APPENDICES ............................................................................................................. 24 
12.1 
PATIENT INFORMATION SHEET /INFORMED CONSENT FORM ......................................... 24 
12.2 
QUESTIONNAIRES....................................................................................................... 24 
 

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PROTOCOL OUTLINE 
 
Working title 
Implementation of pre-exposure prophylaxis (PrEP) in subjects at particular 
high risk for human immunodeficiency virus (HIV) acquisition - an evaluation 
study. 
Study objectives 
 
 
 
 
 
Assess the impact of PrEP on the sexual and psychological health 
of PrEP users 
 
Incidence of sexually transmitted infections (STIs) in PrEP users 
compared to those not taking PrEP 
 
Assessment of drug compliance 
 
Incidence of HIV seroconversion despite PrEP 
 
Frequency and development of drug resistance in subjects who 
HIV-seroconvert (if any) 
Selection criteria 
(abbreviated) 
Inclusion 
1. 
Male, female or transgender persons aged ≥ 18 years who are 
offered or have started PrEP in routine clinical practice, and 2, 3, 4, 
5, 6 or 7 (below). 
2. 
Men who have sex with men (MSM) and transgender persons; 
a. 
who have had unprotected anal sex with two or more 
partners during the last six months and/or 
b. 
who have had bacterial sexually transmittable infection(s) 
during the last twelve months and/or 
c. 
who have used post-exposure prophylaxis(PEP) during the 
last twelve months and/or 
d. 
who use recreational drugs when having sex 
3. 
Indication for PrEP is present according to the assessment of the 
health care provider 
4. 
Men and women who are at high risk of HIV according to their 
sexual practices 
5. 
HIV-negative partner of a HIV-positive person not yet virologically 
suppressed by antiretroviral therapy (ART) 
6. 
Sex workers with inconsistent condom use 
7. 
Persons with inconsistent condom use with sexual partners in / from 
countries with a high prevalence of HIV (COHP) 
 
Exclusion 
1. 
HIV positive subjects 
2. 
Subjects who cannot take FTC/TDF due to contraindications 
 
Control group 
1. 
Enrolled patients will be regarded as their own control when it 
comes to their sexual health and quality of life reported for period 
prior to inclusion in the study.  
2. 
Subjects diagnosed with HIV in general clinical practice and referred 
to the out-patient clinic at the Dept. of Infectious Diseases, OUS, for 
details, see 3.3.2.  
3. 
Frequency of STI reported to the National Institute of Public Health 
(MSIS) will be compared with the frequency of STIs in the study 
cohort. 
Methods & procedures 
PrEP assessment occurs on designated clinic days at The Olafia clinic and 
will be performed by a team of doctors and nurses specifically trained in 
PrEP assessment.  Persons may be self-referred or referred from other 
health providers for PrEP assessment. At other sites this will be organized 
according to the local resources. 
 
Subjects will be provided with written and oral information about the study 
and invited to sign an informed consent form. Subjects not consenting to 
participation in the study will still be offered PrEP (if indicated) and follow up 
according to national (NFIM) and local (Olafiaklinikken) guidelines.  
 
Subjects who sign the consent form will go through an enrolment procedure 
to ensure that the PrEP treatment is indicated according to inclusion/ 
exclusion criteria (based on national and local guidelines).   
Study participants will be asked to complete a questionnaire with detailed 
information on demographics, medical history, sexual behaviour the last  6 
months, perception of HIV risk at the last condomless sex, risk management 
strategies, personal history of STIs, HIV& STI testing frequency and drug/ 

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alcohol use. 
 
Subject will be screened for the following STIs during the enrolment visit; 
HIV, syphilis, hepatitis A/B/C, Chlamydia trachomatis, Neisseria gonorrhoea, 
and Mycoplasma genitalium.  
Participants will be asked to return approximately one week later to discuss 
their HIV result and whether they wish to proceed with initiation of PrEP.   
The decision regarding initiation of continuous or intermittent PrEP is based 
on a discussion with the subject and study team (doctor/nurse), subjects’ 
personal preference, medical considerations and whether the expected use 
will surpass more than 15-20 tablets of FTC/TDF per month.  
HIV testing will be repeated at 2, 4 and 8 weeks from the most recent high 
risk exposure (for HIV acquisition) prior to initiation of PrEP. Thereafter 
participants  are requested to visit the clinic every 3 months from PrEP 
initiation (for the next 24 months) for HIV & STI testing, evaluation of 
compliance (blood test for drug monitoring in continuous PrEP arm, drug 
diaries in both continuous and intermittent PrEP arms), assessment of  
clinical and/or biochemical adverse reactions and quality of life and sexual 
behaviour assessment. Subjects will be asked to answer the same questions 
regarding sexual behaviour and quality of life at follow up visits as at 
inclusion study visit. 
Statistics 
Sample size 
 
Not applicable 
Methods 
Categorical variables will be described by means of absolute and relative 
frequencies, while continuous variables by means of mean, standard 
deviation, quartiles, min and max.  
 

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LIST OF ABBREVIATIONS 
 
AE 
ART 
COHP 
Adverse Event 
Anti retroviral therapy 
Country of high prevalence of HIV 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CSR 
CT 
Clinical Study Report 
Chlamydia trachomatis 
DM 
Data Manager 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EMA 
The European Medicines Agency  
GCP 
Good Clinical Practice 
HIV 
ICF 
Human Immunodeficiency Virus 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IMP 
Investigational Medicinal Product 
ISF 
Investigator Site File 
ITT 
MG 
MSM 
NG 
Intention-To-Treat 
Mycoplasma genitalium 
Men who have sex with men 
Neisseria gonorrhoea 
PI 
Principal Investigator 
PIS 
Patient Information Sheet  
PrEP 
SAE 
Pre-Exposure Prophylaxis 
Serious Adverse Event 
SD 
Standard Deviation 
SDV 
Source Data Verification 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
STI 
TAF 
TDF 
Sexually Transmitted Infections 
Tenofovir alafenamide 
Tenofovir disoproxil fumarat 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
INTRODUCTION 
Pre-exposure prophylaxis (PrEP) is the pre-emptive use of drugs to prevent disease in people 
who have not yet been exposed to the disease-causing agent. In July 2016 the European 
Medicine Agency (EMA) recommended that the EU commission should grant a marketing 
approval for Truvada® (tenofovir disoproxil fumarate + emtricitabine) as PrEP in combination 
with safer sex practices to reduce the risk of sexually acquired HIV infections. The Committee 
for Medicinal Products for Human Use (CHMP) based their decision on clinical trials which 
show substantial reduction in risk for HIV infections when Truvada® was used as PrEP. 
Truvada® is approved for PrEP in USA since 2012. 
 
The introduction of PrEP is mainly based on two studies, the IPERGAY (Molina JM. Et al., 
2015) and PROUD studies (McCormack S et al., 2016). In these two studies Truvada® was 
given ”on demand” or continuously, respectively. The protective effect was comparable in the 
two studies at 86%.   In people who have high risk sex several times per week the risk for HIV 
acquisition is ongoing and continuous HIV protection is required. On the other hand 
individuals who have high risk sex on a predictable, yet infrequent basis may not need 
continuous PrEP. In the latter case intermittent (“on demand”) PrEP may be more 
appropriate. 
 
Intermittent PrEP should reduce cost and the risk of adverse drug reactions as drug exposure 
is minimized. The Norwegian National Guidelines on HIV management (NFIM)  and European  
guidelines (EACS) recommend both intermittent and continuous PrEP as options based on 
the frequency of risk behaviour.  
 
Descovy® (tenofovir alafenamide + emtricitabine) is a newer alternative to Truvada® with less 
risk of renal adverse effects. Many HIV physicians are replacing Truvada® with Descovy® as 
NRTI backbone. Studies are ongoing to evaluate Descovy® as PrEP. 
 
The incidence of bacterial STIs appears to have increased in some settings where PrEP has 
been available, whilst others report a decreased incidence of bacterial STIs in PrEP users. It 
is important to see what implications PrEP will have on the incidence of STIs and sexual 
behaviour of PrEP users in Norway. 
 
Drug resistance is an important factor in HIV treatment. Usually HIV drug resistance occurs in 
an individual as a result of poor adherence to ART.  Alternatively, HIV drug resistance may be 
acquired at the time of transmission if infected by a person already harbouring a resistant 
virus, i.e. transmitted drug resistance. On a worldwide basis, three cases of HIV 
seroconversions despite good PrEP adherence have been reported [Knox D et al. 2016]. In 
one case, the PrEP user was infected by a virus resistant to tenofovir + emtricitabine. 
According to national surveillance data for drug resistance among newly diagnosed patients 
in Norway, the frequency of tenofovir and/or emtricitabine resistance is low: in 2015, two of 
the 149 samples tested were resistant to emtricitabine (1%), and none to tenofovir 
 
In existing guidelines in Europe and US, there is a consensus that PrEP should be made 
available for those at highest risk of HIV infection. This particularly includes men who have 
sex with men (MSM) and male to female transgender persons, based on the incidence of HIV 
infection, individual risk behaviour and other factors affecting sexual behaviour.  
 
The World Health Organization (WHO)’s guidelines for PrEP (from 2015) identify populations 
with a HIV infection incidence of 3 per 100 persons/ year. These include sub-populations of 
MSM, male to female transgender persons and heterosexuals with a HIV positive partner not 
virologically suppressed. The risk will vary and will be evaluated in each individual case.  
 
The European AIDS Clinical Society (EACS) guidelines recommend that PrEP should be 
considered for HIV negative MSM and transgender persons who are inconsistent in their use 
of condoms when having sex with casual partners or HIV positive partners who are not on 
treatment. Centre for Disease Control and Prevention (CDC) in US recommend PrEP to MSM 
with high risk of HIV infection, based on individual risk. As in several other countries, e.g. the 
United Kingdom, The Netherlands and France, the Norwegian Associations for Infectious 

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Diseases has settled on a similar definition of risk and recommend PrEP to the similar target 
populations in its guidelines. 
 
The number of sexually active homosexual, bisexual or other MSM in Norway is unknown. 
Based on previous national and international population studies, the proportion of MSM in the 
male population is estimated to be between 3-7%. Although MSM constitute a relatively small 
proportion of the male population, the group represent more than half of the annual HIV 
cases. This indicates a substantial risk of HIV among MSM.  
 
In the UN’s new political declaration about HIV and AIDS June 2016, MSM were estimated to 
have 24 times higher risk of HIV infection than other adults in the general population. 
Similarly, transgender persons were estimated to have 49 times higher risk of HIV than other 
adults in the general population. PrEP is mentioned in the declaration as one of several 
biomedical interventions that should be considered to reach the goal to eliminate HIV and 
AIDS within 2030.  
 
In EU and EEA there has been an increase in new HIV cases among MSM. 53% of all new 
HIV cases are found among MSM and this group is the only group of the population that show 
an increase in new HIV cases.  
 
Based on the national HIV surveillance figures, MSM are the obvious target group for PrEP in 
Norway as MSM constitute by far the largest single group that contract HIV infection. During 
the period 1986-2016 MSM constituted 32,8% of all HIV cases reported to the National 
Institute of Public Health (NIPH). In 2016 a total of 220 new HIV diagnosis were registered of 
whom 70 acquired their HIV infection in their country of origin prior to immigration and thus 
not eligible for preventive measures. Among the 150 new HIV cases in people residing in 
Norway and eligible to preventive measures,  MSM were over-represented with 87 (58%) new 
HIV infections. he majority of new infections found in MSM occurred as a result of sex with a 
casual partners either in Norway or abroad. An increasing proportion of new infections among 
MSM occurred abroad in 2016 (59%) while new infections among MSM acquired in Norway 
remained stable. 
 
Despite the significant preventive efforts to reduce HIV infections in the past decades, the 
incidence in MSM has plateaued at a higher level after the turn of the millennium. In 2015 a 
reduction in newly diagnosed HIV cases was reported for the first time. Early detection of HIV 
and treatment as prevention may have played a positive role in reducing HIV transmission, 
however, numbers increased again in 2016. Over 90% of HIV positive MSM in Norway are 
treated and virologically suppressed and thereby considered not infectious.  
 
Since the early days of the HIV epidemic, changes in sexual behaviour and increased use of 
condoms have been advocated and the only tools available to prevent HIV transmission. 
Later, frequent testing and treatment of STIs (including HIV) have been added to the 
preventive measures available. Still, this does not seem to be sufficient for all MSM. The use 
of PrEP is therefore likely an important supplement to prevent HIV infections in MSM at high 
risk for HIV acquisition.   
 
In 2016 the incidence of HIV dropped by 30-40% among MSM in London. Participation in 
PROUD and the availability of PrEP (for those who can purchase it privately) has been 
proposed as the main reason for this substantial drop in the incidence [press release 56 Dean 
Street]. 
1.1 
Aim of Present Study 
The main objective of this study is to monitor the impact of PrEP on the subject’s 
psychological and sexual health. It is also important to monitor the adherence to PrEP, 
development of drug resistance (in the case of undetected HIV infection at initiation of PrEP), 
frequency of other STIs, changes in sexual behaviour, recreational drug use and quality of 
life. PrEP has proven to be effective in reducing the sexual acquisition of HIV, however this 
requires that the medication is taken as prescribed, whilst the subject is exposed to high risk 
of infection.  
 

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2 
OBJECTIVES 
This study is designed to evaluated implementation of PrEP treatment as a part of the general 
HIV preventive program in Norway. The target groups are mainly MSM and transgender 
persons at high risk of HIV infection, as well as other subjects at risk of HIV infection due to 
their sexual practices.  
 
Objectives include assessment of the following:  
 
 
Assess the impact of PrEP on the sexual and psychological health of PrEP users 
 
Incidence of sexually transmitted infections (STIs) in PrEP users compared to those 
not taking PrEP 
 
Assessment of drug compliance 
 
Incidence of HIV seroconversion despite PrEP 
 
Frequency and development of drug resistance in subjects who HIV-seroconvert (if 
any) 
 
3 
POPULATION 
3.1 
Inclusion Criteria 
 
In order to participate in the PrEP arm of this study the subjects must meet all of the following 
inclusion criteria: 
 
1. Male, female or transgender persons aged ≥ 18 years who are offered or have started 
PrEP in routine clinical practice, and 2, 3, 4, 5, 6 or 7 (below). 
2. Men who have sex with men (MSM) and transgender persons; 
a. who have had unprotected anal sex with two or more partners during the last 
six months and/or 
b. who have had bacterial sexually transmittable infection(s) during the last 
twelve months and/or 
c. who have used post-exposure prophylaxis(PEP) during the last twelve 
months and/or 
d. who use recreational drugs when having sex 
3. Indication for PrEP is present according to the assessment of the health care provider 
4. Men and women who are at high risk of HIV according to their sexual practices 
5. HIV-negative partner of a HIV-positive person not yet virologically suppressed by 
antiretroviral therapy (ART) 
6. Sex workers with inconsistent condom use 
7. Persons with inconsistent condom use with sexual partners in / from countries with a 
high prevalence of HIV (COHP) 
 
Subjects who are included in the PrEP arm will act as their own controls regarding possible 
changes in psychological and sexual health. At the screening visit they will complete 
questionnaire requesting information related to last 6 months prior to study start. Individuals 
who seroconvert during the observational period will be transferred to the out-patient clinic for 
Infectious Diseases as is already standard of care. 
 
Patients diagnosed with HIV in general clinical practice and referred to the out-patient clinic at 
the Dept. of Infectious Diseases, OUS, will be asked to act as controls to assess their past 
psychological and sexual health. They will be asked to sign the consent form and answer the 
same questionnaire as those in the PrEP arm but not followed further in this study. 
 
Frequency of STI reported to the National Institute of Public Health (MSIS) will be compared 
with the frequency of STIs in the study cohort. 
3.2 
Exclusion Criteria 
 

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In order to participate in the study subjects must not meet any of the following exclusion 
criteria: 
 
1. HIV positive subjects 
2. Subjects who cannot take FTC/TDF due to contraindications 
 
3.3 
Control Group 
Subject to be included in the control group:  
 
1. Enrolled patients will be regarded as their own control when it comes to their sexual 
health and quality of life reported for period prior to inclusion in the study.  
2. Subjects newly diagnosed with HIV in general clinical practice and referred to the out-
patient clinic at the Dept. of Infectious Diseases, OUS, who meet the following 
inclusion and exclusion criteria: 
a. Inclusion criteria in the control group: 
i. Confirmed positive HIV-test, AND 
1. Confirmed negative HIV-test < 12 months ago, OR 
2. Self-reported assumed time of infection < 12 months ago, 
AND 
ii. Resident for > 6 months in a country of one of the following regions 
(EU/EFTA, North America or Australia/New Zealand) at the time of 
confirmed or assumed infection. 
b. Exclusion criteria in the control group:  
i. Confirmed positive HIV-test > 12 months ago, OR 
ii. Self-reported assumes time of infection > 12 months ago. 
3. Frequency of STI reported to the National Institute of Public Health (MSIS) will be 
compared with the frequency of STIs in the study cohort. 
 
3.4 
Recruitment and Screening 
 
Individuals attending the clinic for PrEP assessment are either referred from other health care 
providers or referred by themselves (self-referral).  
Those who have commenced PrEP elsewhere (abroad, purchased themselves, another 
provider) and attend for “PrEP follow-up” either at Olafiaklinikken or a corresponding 
venerological clinic/study site in Norway, may also be included in the study. 
 
Eligible subjects will have the study explained to them, and will receive the written informed 
consent form (ICF). After having had the time to review the nature of the study, they will have 
the opportunity to ask questions to the investigating team. If the subject agrees to participate, 
they will be asked to sign and date one original written informed consent form (ICF). The 
subject will then receive a copy of the signed and dated patient information/informed consent 
form. The original signed ICF will be filed in the Investigator Site File (ISF). The PIS will 
contain site contact information in case of any questions or medical emergency. 
 
Newly diagnosed HIV positive individuals referred to the out-patient clinic of the Dept. of 
Infectious Diseases, OUS, will be invited to participate as controls. The inclusion and 
exclusion criteria for the control group aim at including newly infected individuals (< 12 
months) residing in a country for > 6 months where PrEP might have been available, and 
excluding individuals infected long time ago in a country where PrEP was inaccessible; i.e. 
mostly countries with high HIV-prevalence outside the EU/EFTA-region, North America and 
Australia/New Zealand. They will be presented with the same consent form and questionnaire 
on sexual and psychological health prior to the HIV diagnosis. 
 
Any written information given to potential subjects will be submitted to, and approved by, the 
Ethics Committee(s) prior to implementation. 
 

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3.5 
Subject Withdrawal 
 
In accordance with the Declaration of Helsinki, the Investigator must explain to the subject 
that they have the right to withdraw from the study at any time, and that this will in no way 
prejudice their future treatment. The reason for any kind of withdrawal should be recorded on 
the appropriate CRF. 
 
If a subject is proven HIV positive when using PrEP, the treatment should be stopped 
immediately to prevent development of resistance, registered as a PrEP failure, and referred 
to the Dept. of Infectious Diseases for regular follow-up of their HIV infection and checked for 
resistance to tenofovir disoproxil fumarat and emtricitabine (as is already standard clinical 
practice).  
 
4 
TREATMENT PROCEDURES 
4.1 
Study plan 
The observation will begin after the subjects have signed the informed consent form. PrEP 
treatment should then be initiated when the HIV antibody/antigen test (4th generation test) 
taken at the first visit is confirmed negative.  
However, the window period to rule out HIV infection is 12 weeks. It is not desirable that 
participants are undergoing HIV seroconversion when they commence PrEP, however the 
study population is per definition at high-risk for HIV acquisition. It is likely that the majority of 
the participants not will be in a position to abstain from sex or use condoms effectively for a 
12 week period. Therefore is it is NOT recommended to delay PrEP pending a negative HIV 
test results 12 weeks from the last high risk exposure. International and national guidelines do 
not recommend delaying PrEP initiation in this high risk group for HIV acquisition. Per 
definition, those in need for PrEP are at high risk for HIV acquisition justifying PrEP initiation 
even at first visit. 
For those who have had high risk exposure within 14 days prior to screeing, a HIV-DNA 
provirus test should be requested and the serum test for HIV should be repeated at  2 weeks, 
4 weeks and 8 weeks and 12 weeks  from the day they commenced PrEP.  
 
Subjects that have already commenced PrEP treatment can be included in the study. These 
subjects will be requested to consent to collection of historical medical information from the 
date when the PrEP treatment was initiated.     
 
Follow-up visits are according to clinical practice, clinical judgement and standard patient 
management described in SmPC. For those outside the window period for HIV infection a 
standard visit at 4 weeks and 12 weeks post initiation of PrEP and thereafter every 3 months 
during the PrEP treatment for 24 months. Where clinically indicated the subject may attend 
the clinic between 3 months’ follow-up visits. Data from these visits will be collected as Extra 
Clinical Visits.  
4.2 
Variables 
Subjects will be treated according to local prescribing information and clinical judgement and 
assessments performed according to site clinical practice. The inclusion period will last from 
final approval from The Regional Ethical Committee and until end of 2018. 
 
Data on demographics, sexual health including sexual behaviour, HIV infection status, STIs, 
compliance and recreational drug use will be collected at the baseline visit, 3 months’ follow-
up visits, end of study visit and relevant extra visits. HIV-tests will also be taken at weeks 2, 4 
and 8 in order to identify people in the seroconversion phase at inclusion to reduce risk of 
development of drug resistance. For subjects at particular high risk for HIV infection prior to 
PrEP treatment, HIV-DNA provirus testing will be assessed at the first visit according to the 
doctor’s clinical judgement. As a measure of adherence blood samples will be drawn and the 
tenfovir disproxil fumarate (TDF) concentration in plasma will be measured as well as a self-
reported drug protocol.  

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Investigators are asked to report the requested data in the electronic Case Report Form 
(eCRF).  
 
 
 
 
 
 
 
 
 
 
 
Table 1 Data collection and visit structure 
Study Visits1 
Visit 0 
(evaluation) 
Visit 1(start 
of treatment) 
Visit 2 
(week 
2) 
Visit 3 
(week 
4) 
Visit 4 
(week 
8) 
Follow-up 
visits 
(approx. 
every 3 
months) 
Extra 
visits 
End of study 
visit (24 
months after 
start of 
treatment) 
Clinic visits 
x 
 
 
x 
 
x1 
x 
x 
Informed 
consent 
X 
 
 
 
 
 
 
 
Assess 
eligibility criteria 
x 
x 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
HIV test2 
x 
 
x 
x 
x 
x 
x3 
x 
HIV-DNA 
provirus4 
x4 
x4 
 
 
 
 
 
 
History of STI 
x 
 
 
 
 
 
 
 
STI screening 
x 
 
 
 
 
x 
x3 
x 
Bloodsample 
for TFV-PD 
plasma 
concentration 
 
 
 
x 
 
x5 
x3,5 
x5 
Questionnaire 
sexual 
behaviour (start 
of treatment) 
x 
 
 
 
 
x 
 
x 
Questionnaire 
sexual 
behaviour 
(follow-up) 
x 
 
 
 
 
x 
 
x 
Compliance 
 
 
 
x 
 
x 
x 
x 
Adverse events 
 
 
 
x 
 
x 
x 
x 
Subject diary 
 
 
 
x 
 
x 
 
x 
1 clinic visits to be schedule to fit with PrEP treatment guidelines and local clinical practice. At each visit 
assessments as indicated in table should be captured in the database if they are conducted.  
2 If a subject is infected with HIV during PrEP treatment resistance of the HIV virus for emtricitabin and 
tenofovir disoproxil fumarat should be checked.  
3 If clinically indicated 
4 If high risk sexual contact within the last 14 days 
5 only applicable for subject on continuous PrEP treatment  
 
4.3 
Adverse Events and Serious Adverse Events 
4.3.1 General 
The Investigator should ask the subject questions during the clinic visits in order to ensure 
that appropriate adverse event information is recorded in the subject’s source notes and is 
then subsequently entered into the CRF. Adverse events will be recorded in response to the 
following question - “Since you were last asked have you felt unwell or different from usual in 
any way?” All relevant responses from the subject will be recorded in the CRF on an adverse 

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event form and graded on severity, seriousness and relationship to study medication. For 
further details regarding the classification of adverse events see below. 
Subjects will be questioned regarding any signs and symptoms occurring in the screening 
period and for baseline signs and symptoms prior to the first dose of study medication on Day 
1. Subjects will subsequently be questioned regarding adverse events throughout the study. 
All adverse events are to be reviewed by the Investigator while on-going and subsequently 
documented at the point of resolution. All adverse events classified as serious are to be 
immediately brought to the attention of the Investigator by site staff for review and action in 
accordance with Section 4.4.5 below. 
All on-going adverse events will be followed up by the Investigator until subject discharge or 
resolution. Additional clinic visits may be scheduled by the Investigator to follow-up on 
adverse events according to their clinical judgement. 
 
4.3.2 Seriousness 
 
Adverse Events (AE): any untoward medical occurrence in a subject or clinical trial 
subject administered a medicinal product and which does not necessarily have a causal 
relationship with this treatment. This includes clinically significant laboratory abnormalities 
as judged by the Investigator. 
 
Serious Adverse Events (SAE) are defined as: any untoward medical occurrence or effect 
that at any dose results in death, is life-threatening, requires hospitalisation or 
prolongation of existing hospitalisation, results in persistent or significant disability or 
incapacity, or is a congenital anomaly or birth defect. Events otherwise considered 
serious by the Investigator should also be reported as SAEs. Malignancy would in most 
cases fall into that category. The medical occurrence or effect does not need to be related 
to the study medication. 
4.3.3 Severity 
Severity is classified according to the Common Terminology Criteria for Adverse Events 
(CTCAE v.4.03): 
Grade 1  
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2  
Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental ADL. 
Grade 3  
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self care ADL. 
Grade 4  
Life-threatening consequences; urgent intervention indicated. 
Grade 5  
Death related to AE. 
4.3.4 Relationship to study medication 
 
Unrelated: This category is applicable to those adverse events which, after careful 
medical consideration at the time of evaluation, are judged to be clearly and 
incontrovertibly due to extraneous causes (disease, environment, etc.) and do not meet 
the criteria for study medication relationship listed under remote, possible or probable. 
 
Unlikely: In general, this category is applicable to those adverse events that, after careful 
medical consideration at the time they are evaluated, are judged to be remotely related to 
the test study medication. An adverse event may be considered remote if, or when, for 
example:  (i) it does not follow a reasonable temporal sequence from administration; (ii) it 
could readily have been produced by the subject's clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject; (iii) it does not follow a 
known response pattern to the suspected study medication; (iv) it does not reappear or 
worsen when the study medication is re-administered. 
 
Possible (must have first two criteria): This category is applicable to those adverse events 
which, after careful medical consideration at the time they are evaluated, the connection 
with the test study medication administration appears unlikely but cannot be ruled out with 
certainty. An adverse event may be considered possible if, or when: (i) it follows a 
reasonable temporal sequence from administration; (ii) it could readily have been 

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produced by the subject's clinical state, environmental or toxic factors, or other modes of 
therapy administered to the subject; (iii) it follows a known response pattern to the 
suspected study medication; (iv) it does not reappear or worsen when the study 
medication is re-administered. 
 
Probable (must have first three criteria): This category is applicable to those adverse 
events, which, after careful medical consideration at the time they are evaluated, the 
connection with the test study medication administration appears to, with a high degree of 
certainty, be related to the test study medication. An adverse event may be considered 
probable if: (i) it follows a reasonable temporal sequence from administration; (ii) it could 
not be reasonably explained by the known characteristics of the subject's clinical state, 
environmental or toxic factors, or other modes of therapy administered to the subject; (iii) 
it disappears or decreases on cessation or reduction in dose. There are important 
exceptions when an adverse event does not disappear upon discontinuation of the study 
medication, yet study medication-relatedness exists; e.g. bone marrow depression, fixed 
study medication eruptions, and tardive dyskinesias; (iv) it follows a known response 
pattern to the suspected study medication; (v) it reappears upon rechallenge. 
 
Not assessable: When it is not possible to assign the event to any of the criteria above 
categories. 
4.3.5 Serious adverse reactions and unexpected adverse reactions 
Definitions 
Adverse Reaction: all untoward and unintended responses to an investigational medicinal 
product related to any dose administered. 
Unexpected adverse reaction: an adverse reaction, the nature or severity of which is not 
consistent with summary of product characteristics for Truvada® 
(http://www.ema.europa.eu/docs/no_NO/document_library/EPAR_-
_Product_Information/human/000594/WC500043718.pdf). 
Suspected Unexpected Serious Adverse Reaction (SUSAR): any serious adverse reaction 
that might be related to the study medication and is unexpected according to the definition 
above. 
4.3.6 Reporting of suspected unexpected serious adverse reactions by 
Investigator 
Suspected unexpected serious adverse reactions (SUSARs) will be reported by the 
investigator according to appropriate Competent Authority and Ethics Committee 
requirements. SUSAR reporting to the Competent Authorities and Ethics Committees will be 
performed in writing using CIOMS forms, according to local regulations.  
 
Fatal and life-threatening SUSARs should be reported as soon as possible to the Competent 
Authorities and Ethics Committees according to local regulations, and in any case no later 
than seven calendar days, after knowledge by Investigator of such a case. Relevant follow-up 
information on the case will be subsequently communicated within an additional eight days. 
All other SUSARs shall be reported to the Competent Authorities concerned and to the Ethics 
Committee concerned according to local regulations as soon as possible but within a 
maximum of fifteen days of first knowledge by Investigator. 
 
In addition to the first evaluation of an adverse event that is performed by the investigator, a 
second evaluation with respect to seriousness, causality and expectedness and a risk-benefit 
assessment is performed by ISCR to process safety evaluation according to a four-eye 
principle. 
5 
INVESTIGATIONAL MEDICINAL PRODUCT 
5.1 
Investigational Medicinal Product and Comparator 
 
The following medication supplies will be used in the study: 

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IMP: 
Truvada® 200 mg/245 mg film-coated tablets. Each film-coated tablet contains 200 mg of 
emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg of tenofovir disoproxil 
fumarate or 136 mg of tenofovir). 
 
 
Excipients  
Tablet core:  
Croscarmellose sodium, Lactose monohydrate, Magnesium stearate (E572), Microcrystalline 
cellulose (E460), Pregelatinised starch (gluten free).  
 
Film-coating:  
Glycerol triacetate (E1518), Hypromellose (E464), Indigo carmine aluminium lake (E132)  
Lactose monohydrate, Titanium dioxide (E171).  
 
Marketing authorisation holder and manufacturer: 
Gilead Sciences Intl Ltd. Cambridge CB21 6GT, UK 
 
After the study protocol was sent to The Regional Committees for Medical and Health 
Research 
Ethics 
(REC 
South 
East), 
a 
parallel 
generic 
combination 
tablet 
(Emtricitabine/tenofovir disoproxil Sandoz®) became available in Norway. REC South East 
has been informed about this in an amendment.   
 
Marketing authorisation holder and manufacturer of Emtricitabine/tenofovir disoproxil 
Sandoz®: 
Sandoz A/S, Edvard Thomsens Vej 14, 2300 København S, Danmark 
Subject included in the control group will not receive any study specific treatment.  
 
5.2 
Supply, Packaging, Labelling, Handling and Storage 
 
The subject will receive a prescription on FTC/TDF 200 mg/245 mg for a maximum of 3 
months that will be collected at a regular pharmacy.  
 
Labelling will be done by the pharmacy according to the prescribed dose and local 
regulations.  
 
The subject will bring their remaining medication to the next visit to the clinic for the 
investigator to verify the used number of tablets.  
 
The subjects will report their intake of medication in a paper diary received at the clinic or by 
an app on their phone (Viedocme). The subject should bring their paper diary to the clinic for 
every visit. In addition, plasma levels of either tenofovir or emtricitabine or both will be 
measured on every visit for those subjects enrolled for continuous PrEP as an objective tool 
to assess compliance. 
5.3 
Dosage and Administration 
The subjects are enrolled in this study because they will receive FTC/TDF as PrEP treatment. 
FTC/TDF has a marketing approval in Norway and will be prescribed by the investigator as 
continuous treatment in accordance with the SmPC or intermittently according to the regime 
in the IPERGAY-study (ref) and The National Guidelines for the management and prevention 
of HIV.  
 
Dosing continuous treatment: 1 tablet per day 
 
Dosing intermittent treatment: 2 tablets 2-24 hours prior to sexual contact, and 1 tablet 24 and 
48 hours after sexual contact, but max. 15-20 tablets per month. If in need of more tablets per 
month, national guidelines recommend continuous PrEP. 

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In accordance with the SmPC each subject will together with their physician decide whether 
they will take FTC/TDF every day or intermittent (on demand). Adherence should be closely 
followed during the study period.  
 
Patients with a contraindication to FTC/TDF as a result of e.g. renal dysfunction, will be 
assessed according to standard of care. These patients may be referred to the Dept. of 
Infectious Diseases, Oslo University Hospital, for second opinion and may be included in this 
study if put on FTC/TDF, but not if offered an alternative regimen. 
 
The subjects should be informed that PrEP treatment does not give full protection against HIV 
and offers no protection against other bacterial STIs and therefore should be used in 
combination with condom.  
 
5.4 
Duration of Treatment 
Subject will be followed up for a period of up to 24 months.  
5.5 
Methods for Assigning Subjects to Treatment 
There is no randomisation in this study. The subject will be prescribed PrEP as continuous or 
intermittent treatment as agree with the investigator according to their needs. 
5.6 
Concomitant Medication 
Any medication (prescription as well as over the counter (OTC) drugs) or therapeutic 
intervention deemed necessary for the subject, and which, in the opinion of the Investigator, 
do not interfere with their safety, may be continued unless they are listed in 4.5 Interaction 
with other medicinal products and other forms of interaction of the SmPC.  
 
Any medications, herbal medicines, natural health remedies and nutritional supplements used 
at Screening until Follow-up visit (24 months) are to be recorded in the Concomitant 
medication module in the eCRF system. The generic name of the medication (i.e., not local 
trade names), along with start date, stop date, dose, route, regimen and indication shall be 
recorded as applicable in the eCRF system.  
 
Any new medications or changes to the dose or regimen of pre-existing medications will be 
updated on a routine basis during the study.   
 
5.7 
IMP Accountability 
Medication will be prescribed on a reimbursable prescription and collected at their regular 
pharmacy. Subject will bring their remaining tablets to the clinical visits for the clinic to verify 
their compliance.  
 
6 
VARIABLES 
 
Demographic information (age, gender, race, height, weight, sexuality, education, 
work situation, relationship status) 
 
Sexual behaviour (number of partners, condom use, HIV positive partners) 
 
Sexual transmittable infections (history and current status for infections with syphilis, 
hepatitis A/B/C, Chlamydia trachomatis, Neisseria gonorrhoea, and Mycoplasma genitalium. 
 
Compliance (days tablets taken, days tablets missed, compliance (%), compliance in 
connection with exposure to infection, reason for poor compliance, serum 
concentration of FTC/TDF).  
 
HIV infection status (positive, negative, resistence) 
 
Quality of Life using attached questionnaire 
 
Adverse reaction related to PrEP treatment 
 

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7 
STATISTICAL 
METHODOLOGY 
AND 
DATA 
MANAGEMENT 
7.1 
Statistical Analysis Plan 
 
All analyses will be performed by the Sponsor after the study is completed and the database 
is locked. Statistical programming and analyses will be performed using SAS and/or other 
validated statistical programs. A detailed statistical analysis plan (SAP) will be described in a 
separated document.  
7.2 
Study Populations 
Data will be described on enrolled subjects undergoing PrEP treatment. Subjects who do not 
satisfy inclusion criteria will not be included in the analysis. A summary table reporting 
reasons for exclusion will be provided.  
 
7.3 
Descriptive statistics 
Categorical variables will be described by means of absolute and relative frequencies, while 
continuous variables by means of mean, standard deviation, quartiles, min and max.  
Analyses will consider data collected at variable observational points, according to clinical 
practice and clinical judgement. In order to summarize data by time point the nearest 
available evaluation measurement will be considered (acceptable range).  
 
7.4 
Missing data 
Subjects missing data values will not be excluded from the analysis, but their data will not be 
replaced; frequency of missing data will be given for all analysed variables.  
7.5 
Data Collection / Case Report Forms  
Data will be collected using an electronic data capture (EDC) solution. Electronic Case report 
forms (eCRFs) will be utilised for recording data from each subject meeting the eligibility 
criteria but will not be completed for subjects who fail to meet eligibility criteria. The eCRF 
system, VieDocTM, will be available on an internet portal accessible through any standard 
computer with internet access. A personal log-in will be provided for all responsible personnel 
to allow for an audit trail relating to the study data to be maintained.  
 
For the subject questionnaire at 3 months follow-up and the subject diary there will be an 
option to complete these electronically through the app ViedocMeTM on a smart phone. 
 
The data in the eCRFs should be consistent with the relevant source documents.  The 
Investigator will sign the designated signature fields of the eCRF data entry screens to 
confirm that the information on each screen is accurate and complete. All data must be stored 
in an unidentifiable form treated with strict confidentiality in accordance with applicable data 
protection regulations. 
7.6 
Data Management 
Data will be transmitted electronically into the web based EDC system. Upon receipt, data will 
be coded according to pre-specified dictionaries. The handling of data, including data quality 
control, will comply with all applicable regulatory guidelines. 

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8 
REGULATORY AND ADMINISTRATIVE PROCEDURES 
8.1 
Institutional Review  
The study will be conducted in accordance with the Fortaleza, 2013 amendment to the 
Declaration of Helsinki 1964. 
 
The Protocol and the Patient Information Sheet / Informed Consent Form will be approved by 
the relevant Competent Authorities and Ethics Committees, and possibly other public bodies 
according to local requirements before commencement. If a protocol amendment is 
necessary, this will be prepared with the agreement of the Principal Investigator, and signed 
by the relevant parties. If the amendment is considered to be substantial, it will be submitted 
to the Competent Authorities and Ethics Committees, and possibly other public bodies 
according to local requirements for review and approval. The protocol amendment will not be 
implemented before the required approvals are obtained. Minor amendments which do not 
affect the safety or physical or mental integrity of the clinical trial participants or the scientific 
value of the trial (i.e. non-substantial amendments) will not be submitted to Competent 
Authorities or Ethics Committees.  
8.2 
Patient Information / Informed Consent  
The Investigator is responsible for giving the study subject full and adequate verbal and 
written information about the nature, purpose, possible risk and benefit of the study. Study 
subjects must also be notified that they are free to withdraw from the study at any time. The 
subjects should have reasonable time to read and understand the information before signing. 
The Investigator is responsible for obtaining signed informed consent from all subjects before 
including the subject in any study related procedures. 
 
A signed copy of the patient information and of the Informed Consent Form in local language, 
will be given to the subjects, Appendix 12.1. 
8.3 
Subject Confidentiality 
The Investigator must ensure that subject’s confidentiality will be maintained. eCRFs should 
only identify subjects by their initials and study number. The Investigator should keep a 
separate log of subject codes and names. Documents not for submission to the Sponsor, e.g., 
subject’s completed Consent Forms, should be retained by the Investigator in strict 
confidence. 
 
The Investigator is required to record primary efficacy and safety data, concomitant 
medication and subject progress in the subject’s file/notes/medical record. 
8.4 
Subject Treatment Plan 
It will be possible for the subject to continue with the PrEP treatment after end of the study. 
Subject withdrawing their consent will be offered to continue with the PrEP treatment 
independently of their study participation.  
8.5 
GCP 
The study will be managed and conducted according to the latest International Conference on 
Harmonisation (ICH) guidelines for Good Clinical Practice (GCP). A copy of these guidelines 
can be found in the Investigator Site File (ISF). 
8.6 
Record Retention 
eCRFs and all medical records upon which the eCRF are based (source data) must be kept 
for at least 15 years after completion of the study. Image carriers or other data carriers may 
be used for this purpose. The documentation should be easily retrievable and readable during 
the entire archiving duration. 

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8.7 
Quality Assurance 
During or after the study is completed, sponsor representatives or regulatory authorities may 
wish to carry out an audit or an inspection. These representatives must have the access to all 
study data and subject source data. 
8.8 
Insurance and Liability 
Liability for IMP-induced injury will be according to local requirements. The sponsor will 
indemnify the Investigator in accordance to national regulations. 
8.9 
End of Trial 
The end of the trial is defined as the last visit of the last subject included in the trial. Within 90 
days of the end of the trial, the Sponsor will notify Competent Authorities and Ethics 
Committees the regular termination of the study as required according to national law and 
regulations.  
 
8.10 Study Report 
A study report SR will be prepared covering clinical and statistical aspects and summarising 
all findings of the clinical study. The content has to be treated as strictly confidential. The 
study report will be sent to the Investigators, the Competent Authorities and Ethics 
Committees according to local requirements. 
8.11 Publication and Data Rights 
It is envisaged that the findings of the study will, in due course and by mutual agreement, be 
published in a scientific journal and/or presented at a scientific meeting 
 
The published international guidelines for authorship (International Committee of Medical 
Journal Editors, 1997) will be adhered to; i.e. ‘All persons designed as authors should qualify 
for authorship. Each author should have participated sufficiently in the work to take public 
responsibility for the content.’ 
 
Authorship credit will therefore be based only on substantial contributions to 1) conception 
and design, or analysis and interpretation of data; and to 2) drafting the article or revising it 
critically for important intellectual content; and on 3) final approval of the version to be 
published. Conditions 1), 2) and 3) must all be met. Participation solely in acquisition of 
funding or the collation of data does not justify authorship. General supervision of the 
research group is not sufficient for authorship. It is intended that information on what each 
author has contributed will be published.  
 
It is emphasised however, that only those who entirely meet the above mentioned criteria will 
be listed as authors.   

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9 
REFERENCES 
ECAS guidelines, October 2016.  
 
National guidelines for infectious medicine 2017.  
Knox, D. and others. HIV-1 infection with multiclass resistance despire preexposure 
prophylaxis (PrEP). CROI, 2016. Abstract 169LB. 
 
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: 53–60. 
 
Molina JM., Capitant C., Spire B., et al., for the ANRS IPERGAY Study Group. On-Demand 
Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med 
2015;373:2237-46. 
 

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10 
SIGNATURES 
 
The protocol has been approved by:  
 
 
Name and function 
Signature 
Date 
 
Anne Olaug Olsen 
Principal Investigator 
 
 
 
 
  
 
 
 
 
 

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11 
SIGNATURE PAGE FOR INVESTIGATORS 
 
By signing this page, the Investigator confirms having read the entire protocol and its 
appendices, and agrees to conduct this study in accordance with the protocol, GCP, the 
Declaration of Helsinki and national regulations.  
 
The signature also confirms that the Investigator agrees that the results of this study may be 
used for submission to national and/or international registration and supervising authorities. 
The authorities will be notified of the Investigators name, address, qualifications and extent of 
involvement. 
 
Name 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 

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12 
APPENDICES 
12.1 Patient Information Sheet /Informed Consent Form 
12.2 Questionnaires