Effectiveness of the Use of Personal Protective Equipment in Addition to Tenofovir/Emtricitabine for the Prevention of the Transmission of SARS-COV-2 to Health Care Personnel. Randomized Clinical Trial
Phase: PHASE2
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19
Sponsor: Hospital Universitario San Ignacio

EFFECTIVENESS OF THE USE OF PERSONAL PROTECTIVE EQUIPMENT IN ADDITION TO 
TENOFOVIR/EMTRICITABINE FOR THE PREVENTION OF THE TRANSMISSION OF SARS-COV-2 TO 
HEALTH CARE PERSONNEL. RANDOMIZED CLINICAL TRIAL  
 
Protocol: version 3.0 August-07-2020 
Name and affiliation of principal investigator  
Sandra Liliana Valderrama Beltrán MD Msc.  Pontificia Universidad Javeriana - Hospital 
Universitario San Ignacio. 
Name and affiliation of coinvestigators: 
Pontificia Universidad Javeriana 
Juliana María Cuervo Rojas– Médica MD MSc PhD. 
Martín Rondón - Estadístico MSc. 
María Nelcy Rodríguez Malagón - Estadística MSc  
Hospital Universitario San Ignacio 
Sandra Milena Gualtero Trujillo MD 
María José López Mora MD Msc. 
Claudia Cardozo  
Ana Peñuela  
Ivonne Tatiana Ordóñez Blanco MD 
Sebastián Alejandro Mackenzie Martínez MD 
Juan Manuel Vásquez Jiménez MD 
Hernán Darío Vergara Samur MD Msc.  
Samuel Martínez Vernaza MD 
Clínicas Colsanitas 
Center Principal Investigator: Carlos Arturo Álvarez Moreno MD MSc PhD. 
Claudia Aristizábal Guzmán MD Msc. 
Fredy Orlando Guevara Pulido MD 
Gabriel Alonso Rodríguez Caicedo MD  
Johanna Vargas  
María Alejandra Palacios Ariza MD Msc. 

Hospital Universitario Nacional de Colombia  
Center Principal Investigator: Jorge Alberto Cortés MD 
Hospital Universitario de la Samaritana 
Center Principal Investigator: Katherine Garzón Bedoya MD MSc PhD. 
Carlos Eduardo Pérez Díaz MD MSc 
Carlos Mauricio Calderón Vargas MD 
Hospital San Jorge 
Center Principal Investigator: Karen Ordóñez MD 
Fundación Universitaria Autónoma de las Américas 
Jaime Andrés Cardona Ospina MD MSc 
Universidad del Quindio 
Jorge Gómez Marín MD MSc 
Universidad Tecnológica de Pereira  
Jorge Enrique Machado MD MSc PhD. 
 
Name and Address of the Sponsor  
Ministerio de Ciencia, Tecnología e innovación. Avenida Calle 26 No. 57 - 83 
Torre 8 - Pisos del 2 al 6 
Código postal: 111321 
Teléfono: (57) (1) 6258480 ext. 2081 o 018000914446 
Fax: (57) (1) 6258481 
 
Institutions: 
Pontificia Universidad Javeriana, Bogotá, Colombia. 
Hospital Universitario San Ignacio. Unidad de Infectología. Bogotá, Colombia. 
Clínicas Colsanitas S.A. Bogotá, Colombia. 
Clínica Reina Sofía 
Clínica Universitaria Colombia 
Clínica Santa María de Lago 
Hospital Universitario Nacional. Bogotá, Colombia 

Hospital Universitario de la Samaritana. Bogotá, Colombia 
Red de Hospitales del Departamento de Cundinamarca – Secretaria de Salud de Cundinamarca. 
Fundación Universitaria Sanitas. Bogotá, Colombia. 
Fundación Universitaria Autónoma de las Américas  
Universidad del Quindío  
Universidad Tecnológica de Pereira  
Hospital San Jorge E.S.E Pereira  
 
 
 

List of abbreviations 
 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AZT/3TC 
Zidovudine/lamivudine 
ABC/3TC 
Abacavir/lamivudine 
CDC 
Centers for Disease Control and Prevention.   
Cels/μl 
Cells per microliter  
CRF 
Case Report Form 
CTCAE 
CTCAE, Common Terminology Criteria for Adverse Events 
DAIDS 
DAIDS Adverse Event Grading Tables 
BD 
Bone density  
AE 
Adverse Event  
EFV 
Efavirenz 
ELISA 
Enzyme-linked immunosorbent assay 
PPE 
Personal protective equipment  
FDA 
Food and Drug Administration 
Hb 
Hemoglobin 
MSM 
Men sex with men  
HUSI 
Hospital Universitario San Ignacio 
INR 
International standardized ratio 

IPS 
Health care provider institution  
IRB 
Institutional review board 
ULN 
Upper normal limit (with regards to lab testing ) 
mg/dl 
Milligrams per deciliter 
WHO 
World Health Organization  
PTT 
Partial Thromboplastin Time 
PUJ 
Pontificia Universidad Javeriana  
PrEP 
Pre-exposure prophylaxis  
RT-PCR 
Real time polymerase chain reaction.  
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SOP`s 
Standard Operating Procedures 
TDF/FTC 
Tenofovir Disoproxil fumarate and Emtricitabine 
TLR 
Toll-like receptor 
UAA 
Universidad Autónoma de las Américas 
ICU 
Intensive Care Unit 
UQ 
Universidad del Quindío 
UTP 
Universidad Tecnológica de Pereira 
HIV 
Human Immunodeficiency virus  
HBV 
Hepatitis B virus  
 
 
 

Summary of the study  
Title   
Effectiveness of the use of Tenofovir/Emtricitabine in addition to 
personal protective equipment for the prevention of the 
transmission of SARS-COV-2 to health care personnel. A 
Randomized Clinical Trial. 
Study population 
Health care professionals (Physicians, Nurses, Respiratory therapists, 
or nursing assistants) between older than 18 years and less than 70 
years, who provide health care to confirmed or suspected cases of 
COVID-19 in the emergency room,  COVID wards, or the intensive 
care units from seven hospitals in Colombia. 
Study design   
Randomized triple-blinded multicentric clinical trial to evaluate the 
effectiveness and safety of Tenofovir/Emtricitabine in addition to 
personal protective equipment for the prevention of infection with 
SARS-CoV-2 in health care personnel in Colombia. 
General Objective  
To evaluate the effectiveness and safety of Tenofovir/Emtricitabine 
in addition to the use of Personal Protective Equipment (PPE) for the 
prevention of SARS-CoV-2 infection in health care personnel who 
provide health care to confirmed or suspected cases of COVID-19 in 
the emergency room, COVID wards and ICU.  
 

Specific Objectives   
- 
To 
determine 
the 
effectiveness 
of 
Tenofovir 
Emtricitabine in addition to the use of Personal 
Protective Equipment (PPE) for the prevention of SARS-
CoV-2 infection in health care personnel caring for 
patients with confirmed or suspected COVID-19 in the 
emergency room, general ward and ICU.  
- 
To evaluate the safety (adverse events frequency) of 
Tenofovir Emtricitabine in addition to the use of Personal 
Protective Equipment (PPE) for the prevention of SARS-
CoV-2 infection in health care personnel caring for 
patients with confirmed or suspected COVID-19 in the 
emergency room, general ward and ICU.  
- 
To evaluate the adherence to Tenofovir Emtricitabine of 
health care personnel caring for patients with confirmed 
or suspected COVID-19in the emergency room, general 
ward, and ICU.  
- 
To determine the frequency of discontinuation for any 
reason of Tenofovir Emtricitabine in health care 
personnel caring for patients with confirmed or 
suspected COVID-19 in the emergency room, general 
ward, and ICU.  
- 
To describe and compare the clinical course and severity 
of participants who develop COVID-19 in the 
intervention and control groups. 
Primary Outcome   
Incidence of SARS–CoV-2 infection in health care personnel caring for 
patients with confirmed or suspected COVID-19 
Sample size   
950 healthcare workers randomized 1 to 1 to the intervention group 
(Tenofovir Emtricitabine + PPE), or the control group (Placebo + PPE).  
475 in each group 
 
 
 
 

 
1. 
Background and Problem Formulation  
1.1. 
Approach and justification  
The global impact of SARS-CoV-2/COVID-19 is unprecedented, and it is the greatest pandemic of a 
respiratory virus since the 1918 Influenza. With high infectiousness, important morbidity and 
relatively high fatality in specific groups of the population, an attack rate of approximately 80%(1), 
and no vaccine available yet, the pandemic will exceed the capacity of the health care systems in 
many settings. The health care personnel represent the most valuable resource to respond to the 
challenges imposed by this pandemic. As health care professionals are in the frontline of response 
and at a high risk of infection, it is extremely important to establish effective prevention strategies 
that protect them from becoming infected (2).   
The main mode of transmission for SARS-CoV-2 infection is person to person through direct 
contact, droplets, or fomites. Moreover, aerosol-generating procedures have also been 
documented to transmit the infection (3,4). In countries such as Italy, where the pandemic had an 
accelerated behavior and high mortality rates, it has been estimated than from the total of 
infected people 7-9% corresponds to health care workers (5). Additionally, data from China and 
The USA show that between 3.8 and 19 % from the total of infected people are health care 
personnel, respectively (5-7). First, not only do They represent the initial barrier of response in any 
epidemic which increments by itself the exposition to the pathogen but by having asymptomatic 
infected individuals use of proper personal protective equipment may be missed.  
Both hand hygiene and the use of Personal Protective Equipment (PPE) such as surgical gown, 
gloves, ocular protection, surgical mask, or N-95 respirator, are considered key strategies for the 
prevention of infection in health care professionals (8). However, there are few studies estimating 
the probability of infection with their use. Moreover, several pharmacological agents have been 
considered for a prophylactic use in SARS-CoV-2 infection. 
As of today, there is preclinical evidence, principally in vitro, indicating antiviral effect of Tenofovir 
Disoproxil Fumarate / Emtiricitabine (TDF/FTC) on the SARS-CoV-2 RNA depended RNA polymerase 
(9). TDF/FTC is an approved drug for HIV treatment in combination with other antiretroviral drugs. 
It is widely used as HIV pre and post exposure prophylaxis, and it is the election therapy for 
Hepatitis B infection (10-13).  
Knowing that TDF/FTC is a drug with a known security profile, has low frequency of short-term 
adverse events, and is capable of inhibiting SARS-CoV-2 replication in vitro, it is an interesting 
alternative to evaluate as prophylaxis for SARS-CoV-2 infection. On the other hand, in Spaniard HIV 
programs it has been noticed that in HIV positive patients under antiretroviral therapy, even those 
older than 50 years, a lower burden of covid-19 is observed compared to general population (14), 
despite of chronic inflammation and rapid immunosenescence, which is characteristic in this type 
of population (15). Furthermore, recently, in a clinical cohort of 77590 persons living with HIV, it 
was documented that those receiving TDF/FTC had a risk of COVID 19 and related hospitalization 
between 37 a 57% lower than those who were taking other antiretroviral medications.  

Nevertheless, this observation must be evaluated rigorously, considering that it might be possible 
this population, knowing their risk, could have been more adherent to preventions measurements.   
Consequently, we consider relevant and justified to evaluate the use of TDF/FTC for the prevention 
of SARS-CoV-2 infection in a high-risk population, such as health care professionals providing clinical 
care to confirmed or suspected cases of COVID-19 through a clinical trial. Thus, allowing to establish 
prevention strategies with higher scientific evidence.  
1.2. 
Research question 
What are the effectiveness and safety of Tenofovir/ Emtricitabine in addition to the use of Personal 
Protective Equipment (PPE) for the prevention of SARS-CoV-2 infection in health care personnel who 
provide clinical care to confirmed or suspected cases of COVID-19 in the emergency room, COVID 
wards and ICU? 
1.3. 
Theoretical framework  
In December 2019 at Wuhan, the capital city of Hubei Province in China, there was a report of a 
conglomerate of pneumonia cases that alarmed health authorities of this country (16). Later, it was 
identified that the etiology of this acute respiratory infection is a novel coronavirus (SARS-CoV2) 
which shares some molecular characteristics with MERS-CoV (Middle East Respiratory Syndrome) 
and SARS-CoV1 (acute severe respiratory syndrome) (17) 
The disease caused by SARS-CoV2 known as COVID-19 has a wide range of manifestations that vary 
from asymptomatic individuals to patients developing acute respiratory distress syndrome (ARDS). 
Also, it has been reported extrapulmonary manifestations such as gastrointestinal, dermatological, 
and CNS involvement (16,18). Some risk factors for mortality have been described, for instance, D-
dimer greater than 1ug/ml, high SOFA score, and Advanced age (19). 
Outbreaks from familial clusters in which the virus has been able to be identified have been 
described (20). To date there is no estimative of prevalence in asymptomatic patients due to the 
difficulty in identification techniques. Nevertheless, it has been documented that viral load is higher 
at the onset of symptoms indirectly pointing that transmissibility initiates 2.5 days before the 
initiation of symptoms which implies that people who develop symptoms could be infective even 
before that happens (18). 
The epidemic has extended rapidly through the globe due to its high basic reproductive number, 
estimated on average between 2.5 to 3.6, this obtained from mathematical modeling (2,21,22). The 
burden of disease is serious making health systems exceed maximum capacity (22). According to the 
Pan-American Health Organization (PAHO) as of July 5th, there were 5.697.954 cases alone in the 
Americas with 262.538 deaths (23). In Colombia, the first case was reported on March 6 with a 
tendency to rise. Since then, multiple public health measures were taken gradually expecting to 
reduce transmissibility in the upcoming weeks. According to the Colombian National Institute of 
Health (INS), there has been an exponential increase in reported cases with data as of June 9 of 
40.719 confirmed cases and 1.308 confirmed deaths (24). 

The pandemic has presented a huge economic impact globally. The economic effect of this crisis is 
estimated to be serious and profound. Only the closure of Wuhan, a large financial center in 
mainland China, meant the suspension of activities of multinationals and the collapse of multiple 
stock markets around the world since before the internationalization of the epidemic (25). Although 
the extent of the current crisis is not yet known, it could be extrapolated from previous coronavirus 
outbreaks such as MERS in 2015, for which losses of approximately $ 2.1 billion were estimated for 
tourism alone in the Republic of Korea (26). This outbreak was much smaller in terms of victims and 
geographic size. Meanwhile, the less conservative projections project declines in global GDP growth 
for the first quarter of zero and a substantial decline in growth in the world economy for the full 
year (25,277).  
Natural history of SARS-CoV-2 / COVID 19 
-Incubation period  
Studies performed in confirmed cases of COVID-19 estimate an average incubation period of 5.5 
days with a maximum expected of 12-14 days after the contact has occurred (28). Only between 1 
to 5 % of reported cases will exceed that period of time thus making epidemiologic surveillance 
documents recommend a 14 day follow up after being in contact with an infected person (29-33).   
-Previous period to onset of symptoms in which it is considered that persons can transmit the virus 
The exact duration of the asymptomatic period in which the virus can be transmitted is unknown. It 
is estimated that this could be between 2 to 5 days prior to the onset of symptoms. Moreover, 
studies of follow up to close contacts state that an attack rate of 0.7 to 6.4% could be in this period 
(34,35). A mathematical model made in China establishes that infectivity is much higher in early 
stages of SARS-CoV-2 infection, initiating on average 2.3 days prior to the onset of symptoms with 
a peak at the day 0.7 after presence of symptoms and a considerable drop close to day 7 after 
initiation of symptoms (36).  
-Calculated percentage of asymptomatic patients   
There is still no clarity about the percentage of asymptomatic cases which increments the 
uncertainty and generates greater difficulties in order to establish infection control effective public 
health policies. Screening studies in confined population show frequencies of asymptomatic 
infected individuals between 18-46.5% (37). Nevertheless, surprisingly, up to 50% of these 
individuals could have radiological manifestations of COVID-19 (38,39).  
-Average time of symptoms duration 
The International Otorhinolaryngology Federation performed an observational study in which 1. 420 
mild-moderate COVID-19 cases were assessed for describing clinical and epidemiological 
characteristics in Europe. The most frequent symptoms were Cephalalgia(70.3%), anosmia (70.2%) 
nasal congestion (67.8%), cough (63.2%), myalgias (62.5%), rhinorrhea (60.1%), dysgeusia (54.2%), 
odynophagia (52.9%) and fever (45.4%), respectively. Mean duration of symptoms was 11.5±5.7 
days (40).  

The China Medical Treatment Expert Group for COVID-19 retrospective cohort described 1.099 
patients with SARS CoV 2 confirmed infection finding that up to 88.7% of hospitalized patients 
developed fever followed by 67.8% of patients that developed cough. Mean duration of hospital 
stay was 12.8 which would correspond with the symptomatic period (41).  
Impact and prevention measures in health care workers  
The contagion in health care workers has been a critical point in the COVID-19 pandemic. Some 
series report that up to 19% of contagions occur in the health care setting (42). The main basic 
prevention measure is the use of personal protective equipment (PPE). Both WHO and the CDC 
recommend the use of standard precautions of contact and droplets with complete facial protection 
or at least ocular protection (42,43). Aerosol Isolation measurements are required only in the case 
of aerosol-generating procedures, such as orotracheal intubation or extubation, bronchoscopy, non-
invasive mechanical ventilation, nebulization, Cardiopulmonary resuscitation, or endoscopy (21).  
For its part, the CDC recommends that patients with suspected or confirmed COVID-19 be cohorted 
in individual rooms with a door and an exclusive bathroom (42). 
Special attention is given to the placement and removal sequence of PPE in order to avoid contagion 
when manipulating them.  The effectiveness of the adequate use of PPE has not been established 
by a clinical trial, however, it is known that it is a protective factor for COVID-19 (44). Nevertheless, 
shortage of PPE, PPE re use necessity and PPE use errors (especially when taking them out) might 
facilitate hand and mucous contamination, which may contribute to its ineffectiveness (45).  
According to a report of the Colombian Social Protection Ministry, as of May 1st, 2020 6.5% of the 
total COVID-19 cases were from health care workers. A total of 459 cases from which 30.1% were 
nurse assistants, 23.7% were medical doctors, 15% were nurse practitioners and 2.4% were 
Respiratory therapists. Most of the cases were in Bogota (35.9%) followed by Risaralda (20%) and 
Cali (9.6%). Data on the burden and incidence of COVID-19 for health care workers is limited. Data 
from china reported an incidence of 38.9 per 100 exposed health care workers and 6 to 11.6 per 
100 hundred health care workers in Madrid and The Netherlands respectively (7,44).  
 
Tenofovir/Emtricitabine as prophylaxis for SARS-CoV-2 Infection  
SARS-CoV-2 is a single strand positive-sense RNA virus similar to Hepatitis C Virus, West Nile Virus, 
Marburg, HIV, Ebola, Dengue virus, and Rhinovirus, among others. The RNA-dependent RNA 
polymerase (RdRp) is one of the structural proteins of SARS-CoV-2(46). The active site of RdRp is 
configured by two successive aspartate residues which protrude from a beta turn structure, making 
accessible to the surface through the nucleotide canal (47). The homology between SARS-CoV-2 
RdRp and SARS-CoV-1 is higher than 97%, thus facilitating in silico studies (48). 
Elfiky et al.  made an RdRp SARS-CoV-2 model based on different available structures in protein 
banks. Using it and through simulation, they documented the theoretical effectiveness of several 
antiviral agents such as IDX-184, Sofosbuvir, Ribavirin y Remdisivir, and TDF/FTC for the inhibition 
of RdRp (47,49).  

The antiretrovirals used in the treatment of HIV infection have been previously studied in vitro and 
in vivo for SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory 
Syndrome) (50,51). Particularly, in this pandemic some observational studies have identified a 
smaller number of patients with HIV acquiring COVID-19 in comparison to the general population 
which has brought attention to the scientific community (52).  
In silico studies have identified antiretroviral drugs with potential capability of binding the catalytic 
center of RdRp such as Nucleoside Reverse Transcriptase Inhibitors: abacavir, emtricitabine, 
lamivudine, zidovudine and tenofovir, also protease inhibitors such as: lopinavir, ritonavir , 
saquinavir and the booster cobicistat (53-55). This information has been confirmed in vitro studies 
for TDF, which acts as analogue of a nucleotide that early finishes the replication of the RNA strand 
(55). 
Cytotoxic and antiviral effects of some of the molecules have been evaluated in fibroblasts from 
human lung cells. For tenofovir and emtricitabine (TDF/FTC) the EC50 and the TC50 higher than 100 
µM, however, it is inferior compared to remdesivir which might be explain for the type of assembling 
to the RdRp in each case (48). 
Furthermore, Park, et al. developed an animal model of SARS-CoV-2 in ferrets in which the 
pathogenicity, transmissibility, and lung damage caused by the virus were demonstrated. In an 
experiment using this model, the virus was inoculated by the intranasal route, and a day after, 
numerous molecules with potential antiviral effect were administrated. These molecules were: 
Lopinavir/Ritonavir, Hydroxychloroquine, TDF/FTC. The duration of the intervention was 14 days 
and the ferret group given TDF/FTC presented lower temperature compared to the control group, 
and also an earlier recovery from signs including cough, rhinorrhea, and reduction of activity. 
Moreover, a lower load of virus was detected in the nasal samples from ferrets in the intervention 
group.  From the drugs studied TDF/FTC showed the best results in reducing clinical signs and 
clearing nasal viral shedding (46). 
Tenofovir/Emtricitabine is an antiviral that has been widely used for quite a long time in HIV pre 
exposure prophylaxis (PrEP) and treatment for hepatitis B with a known security profile and minimal 
incidence of adverse events (10-13). Its inhibitory effect on the RdRp of SARS CoV 2 shown in silico 
studies is added to some animal models which makes it a promising alternative in a high risk COVID-
19 population scenario. To date there are two ongoing clinical trials, one in Spain and the other in 
Argentina aiming to prove the effectiveness of TDF/FTC in the prevention of SARS CoV 2 infection. 
(See appendix 1).  
Diagnostic testing  
Various diagnostic tools based on the natural history of the diseases and experience obtained from 
other viruses have been proposed to have rapid results on the diagnosis status of the patient. 
Nevertheless, the power of viral identification varies according to the dynamics of the disease (57).  
Available testing alternatives are viral RNA detection by real-time polymerase chain reaction (RT-
PCR), viral antigen detection in nasopharyngeal swabs, specific antibodies detection, and viral 
culture. Antigen viral detection has low sensitivity in previous experience with HCovs, however, 
there are studies ongoing with good yield according to with the reports of Diao et al. which 

establish that the sensitivity is adequate in patients with 3-day fever, still at publishing stage (57). 
For its cost time and biosecurity required the viral culture has a research application but not a 
clinical one (57).   Thus, basing the clinical diagnoses in the method RT-PCR and antibody 
detection.  
 
During the COVID-19 outbreak, the RT-PCR has been one of the most used testing tools. Corman et 
al at Charité Hospital in Germany developed an RT-PCR identifying E and RdRP viral genes with a 
sensitivity greater than 95% and a specificity of 100% (58). It is important to clarify that detection 
varies from the site of the testing sample being positive in 32% of oropharyngeal swabs, 62% in 
nasopharyngeal swabs, and 80% from bronchoalveolar lavage. Only 15% of patients with 
pneumonia had positive serum RNA (59,60). 
In symptomatic patient the viral load has its peak at the first week of symptoms (60% sensitivity 
before day 11), usually, around day 4 with a gradual decline starting on the second week, still 
being detectable in up to 33% of patients. The median of negativization is 24 days (IQR: 18-31 
days) being lower in COVID-19 mild to moderate (13 days) and higher in critical patients (31 days) 
with detectable viral loads between 42 to 48 days after the onset of symptoms (36,61-64). 
Nevertheless, despite of the longtime of detectable viral load, there are studies suggesting that 
the viral culture negativize at day 8 from the onset of symptoms independently of initial viral load 
(65). 
With regards to antibody detection, it is important to know that according to a Cochrane 
Systematic review, the yield of the different test available depends on the onset of symptoms and 
sample taking. IgG and IgM sensitivity at day 15 from the onset of symptoms is 75.4% and 88.2% 
respectively, whereas, at day 21 from the onset of symptoms is 99.1% and 98.7% (66). Although, a 
recent published study found a seroconversion rate of 10% in asymptomatic contacts evaluated 
after 14 days from the onset of symptoms, there is not certain data of sensitivity and specificity of 
this tests in asymptomatic people (67). 
The detection of antibodies has been described even at the onset of symptoms; however, the 
general total antibody seroconversion starts at day 4 from the onset of symptoms. When 
evaluating IgM seroconversion, a 5-day median of positivization  (IQR:3-6 days) with a sensitivity 
around 50% at day 7, higher than 70% after day 8 and highest after day 10 with a progressive 
decline over the next month (68) . For IgG the positivization increases after day 9 with a median of 
14 days (IQR:10.18 days) with a sensitivity between 80 to 95% at day 15 and 98 to 100% between 
the third and fourth week after the onset of symptoms with an IgG duration yet unspecified (68-
73). Serologic testing may present crossed reactions with SARS-CoV explained by a 90.5% 
coincidence in the genomic sequence (74). 
Data available on diagnostic testing is based on symptomatic patient. It has been described on 
several occasions since the beginning of the pandemic asymptomatic people with positive RT-PCR 
in respiratory secretions (69,70). However, the RT-PCR sensitivity and the ideal moment to perform 
it remains unclear with report as low as 24.3% (75).  

Taking into consideration everything that has been discussed previously, we establish a research 
proposal in which it is planned to evaluate the efficacy and safety of Tenofovir/Emtricitabine and 
adequate use of PPE as a preventive measurement for COVID-19 in health care personnel.  
2. 
Objectives 
2.1. General Objective 
To evaluate the effectiveness and safety of Tenofovir/ Emtricitabine in addition to the use of 
Personal Protective Equipment (PPE) for the prevention of SARS-CoV-2 infection in health care 
personnel who provide clinical care to confirmed or suspected cases of COVID-19 in the 
emergency room, COVID wards and ICU.  
2.2. Specific Objectives   
 To determine the effectiveness of Tenofovir Emtricitabine in addition to the use of 
Personal Protective Equipment (PPE) for the prevention of SARS-CoV-2 infection in 
health care personnel caring for patients with confirmed or suspected COVID-19 in the 
emergency room, general ward and ICU.  
 
● To evaluate the safety (adverse events frequency) of Tenofovir Emtricitabine in addition to the 
use of Personal Protective Equipment (PPE) for the prevention of SARS-CoV-2 infection in 
health care personnel caring for patients with confirmed or suspected COVID-19 in the 
emergency room, general ward and ICU.  
● To evaluate the adherence to Tenofovir Emtricitabine of health care personnel caring for 
patients with confirmed or suspected COVID-19in the emergency room, general ward, and ICU.  
● To determine the frequency of discontinuation for any reason of Tenofovir Emtricitabine in 
health care personnel caring for patients with confirmed or suspected COVID-19 in the 
emergency room, general ward, and ICU.  
● To describe and compare the clinical course and severity of participants who develop COVID-
19 in the intervention and control groups. 
3. Methodology 
 
3.1. 
Study design 
Randomized triple-blinded multicentric clinical trial, conducted in parallel, with to arms:  
The trial Will be performed with health care workers ( Physicians, Nurses, Respiratory therapists, or nurse 
assistants) free of SARS-CoV-2 infection prior, recent or at the time of the inclusion and who directly care for 
confirmed or suspected cases of COVID-19 in the emergency room, general COVID wards or intensive care units. 
A screening at baseline will de carried out in order to evaluate for eligibility by performing:  SARS-CoV-2 RT-
PCR, SARS-CoV-2 IgG antibodies, as well as, hemogram, creatinine, serum phosphorus, AST, ALT, 
ELISA for HIV, surface Hepatitis B antigen antibodies, qualitative pregnancy test (b-HCG). Once 

eligibility is verified participants will be randomly assigned to either an intervention or a control 
group.  
The interventions consists in the administration of Tenofovir/  Emtricitabine  ( 300 mg / 200 mg daily 
during 60 days) + Personal Protective Equipment (PPE) and the control consists in the administration 
of placebo (1 tablet daily during 60 days) + Personal Protective Equipment (PPE) 
All participants will have PPE recommended for the preventions of COVID-19 by the WHO which 
include mayo dress, nonfluid   long sleeve gown, ocular protection with googles, face shield or visor 
and surgical mask in procedures that do not aerosolize. N-95 respirators are required for procedure 
that generate aerosols. For detailed description see Table 2.   
The re-use of N-95 respirators will be allowed according to CDC and WHO guidelines. This taking 
into consideration the shortage of supplies for the actual situation. The N-95 continuous use will be 
for 8 hours and the N-95 intermittent use will be allowed up to 5 times with the precaution of 
storage in a paper and plastic bag label them with the participant name and placed them in a plastic 
recipient at the end of shifts(48).   
After baseline evaluation and confirming eligibility an initial visit and 4 follow up visits at day 20, 40, 
60, 75 days will be carried out. See Table 1 and Graph 1.  
In the case of presenting COVID-19 related symptoms at any time after enrolling a  SARS-CoV2  RT-
PCR will be performed between day 1 to 5 of the onset of symptoms and will be repeated it after 72 
hours in case that the first one is negative. In the case of having any positive SARS-CoV2 RT-PCR or 
SARS-CoV2 IgG SARS-CoV2 infection will be confirmed and the intervention will be suspended.  
On the other hand, the participant who develop symptoms and has one or two negative SARS-CoV2 
RT-PCR the intervention will not be suspended with an exception if the participant requires 
hospitalization with a high clinical suspicion. For his group of participants, a SARS-CoV2 IgM and IgG 
antibodies will be performed at day 14 from the onset of symptoms. If they are positive, the 
participant Will be considered as a positive case of COVID-19.  
3.2. 
Study population  
-Reference population: Health care professionals (Physicians, Nurses, Respiratory therapists, 
or nurse assistants) between the ages of 18 and 70 years, who directly care for confirmed 
or suspected cases of COVID-19 in the emergency room, general COVID wards or intensive 
care units. 
-Eligible population: 
Inclusion criteria  
 Medical doctor, Nurse, Respiratory therapist, or nurse assistant who work in the 
emergency room, general COVID-19 ward, or intensive care unit  
 Age: between 18-70 years  
 RT-PCR and serology tests for SARS-CoV-2 negative at baseline evaluation 

 Direct care of patients in the emergency room, general COVID-19 ward, or intensive 
care unit 
 Informed consent signed  
Exclusion criteria  
● 
Two or more of the following  
 Body temperature higher than 38 Celsius  
 Cough of recent onset (in the previous 10 days) 
 Dyspnea 
 Odynophagia 
 Malaise, fatigue  
 Acute diarrheal disease 
● 
History of COVID-19 confirmed by RT-PCR or IgG antibodies  
● 
Family member with suspected or confirmed COVID 19  
● 
cohabitating with a suspected or confirmed case of COVID-19  
● 
Hepatitis B anti-surface antigen antibodies lower than 10mU/ml at baseline 
evaluation 
● 
Acute or chronic Hepatitis B  
● 
Confirmed diagnosis of HIV infection either by clinical history or ELISA immunoassay 
at baseline evaluation 
● 
Use of TDF/FTC in the last three months for other clinical conditions 
● 
ALT or AST higher than 2 times the upper reference limit  
● 
Serum hemoglobin <11g/dl or neutropenia<1.000cell/mm3 
● 
Renal dysfunction defined as eGFR lower than 60ml/min (using the CKDEPI formula) 
or history of Chronic kidney disease  
● 
Known hypersensitivity to TDF/FTC 
● 
Serum phosphorus level <2.5mg/dl 
● 
Use of the following medications (for detailed description see appendix 2):  
● 
Uso de los siguientes medicamentos (See appendix 2 for detailed description): 
Cidofovir, Celecoxib, Diclofenac, Ibuprofen, Methadone, Naproxen, Nimesulide, 
Piroxicam, 
Amiodarone, 
Quinine, 
Amikacin, 
Cephalexin, 
Clarithromycin, 
Gentamicin, Piperacillin / Tazobazorcin, Flucomycin, Sulfadiazine, Vancomycin , 
Ganciclovir, Ledipasvir / Sofosbuvir, Sofosbuvir / Velpatasvir, Furosemide, 
Hydralazine, Sacubitril, Verapamil, Interferon, Hydroxyurea, Dolutegravir / 
Lamivudine Abacavir, Didanosine, Lamivudine, Atazanavir / cobicistat, Atazanavir / 
ritonavir, Darunavir / ritonavir, Darunavir / cobicistat, Indinavir, Interferon, 
Hydroxyurea, Cyclosporine, Mycophenolate, Sirolimus, Tacrolimus, Acetazolamide 
Orlistat, Probenecid, Pyridostigmine, Sevelamer, Zoledronic acid. 
● 
Diagnosed osteopenia or osteoporosis 
● 
History of pathological fractures 
● 
Pregnancy, lactation, or pregnancy desire during the period of the study 
● 
Being a participant in another Clinical trial of prevention for COVID-19 

-Source population: Health care professionals (Physicians, Nurses, Respiratory therapists, or nurse 
assistants) between the ages of 18 and 70 years, who directly care for confirmed or suspected cases 
of COVID-19 in the emergency room, general COVID wards or intensive care units from seven health 
care institutions in Colombia (Hospital Universitario San Ignacio, Clínica Reina Sofía, Clínica 
Universitaria Colombia, Clínica Santa María de Lago, Hospital Universitario Nacional, Hospital 
Universitario de la Samaritana. Sede Bogotá y Hospital Universitario de la Samaritana. Sede 
Zipaquira, Hospital Universitario San Jorge de Pereira). 
 
3.3. 
Result and primary Outcome   
Primary Outcome  
 
SARS–CoV-2 infection defined as:  
 
-  Detection of SARS–CoV-2 nucleic acid using RT-PCR in any of the specimens collected during the 
study-follow-up including the asymptomatic participant 
-Positive IgG antibodies against SARS–CoV-2 in any of the specimens collected during the study-
follow-up 
 
     Secondary outcomes  
 
- Serious and non-serious adverse events  
- Discontinuation of using the intervention (TDF/FTC or placebo) for any reason 
- Adherence to TDF/FTC defined as: number of tablets taken/total number of dispensed tablets  
- Severity of SARS-CoV-2 infections according to the following categories: 
 
- Asymptomatic infection. 
 
- Mild symptomatic SARS-CoV-2 infection with no need for hospitalization. 
 
- Moderate symptomatic SARS-CoV-2 infection that requires hospitalization, but no ICU. 
 
- Severe SARS-CoV-2 infection: dyspnea with other SARS-CoV-2 symptoms requiring ICU 
hospitalization. 
 
 

Graph 1. Flowchart of assignations and follow up of the clinical trial.  
 
 
 
 
 
 
 
 
Invitation to participate  
 
Initial evaluation 
 
Explaining of objectives, potential risks and benefits 
 
Eligibility evaluation 
-Clinical evaluation 
-RT-PCR, IgG antibodies and blood chemistry 
sampling  
Randomization 
 
Gruop A 
 
Group B 
 
. SARS-CoV-2 RT-PCR will be performed at any 
time of the study if symptoms are present  
 
Visit 1: follow up at day 20: clinical follow up, adverse events and adherence  
 Visit 2:  follow up at day 40: clinical follow up, adverse events and adherence. SARS-CoV-2 
IgG antibodies and creatinine.
 Visit 3: follow up at day 60: clinical follow up, adverse events and adherence. SARS-CoV-
2 RT-PCR. Hemogram, creatinine, AST, ALL; b-HCG in women 19 
 
Visit 2:  follow up at day 75: clinical follow up, SARS-CoV-2 IgG antibodies 
End of follow up  
Evaluation of the severity of infection if applicable  

 
3.4. 
Sample size 
An estimative of the number of required participants was done according to the following 
parameters:  
● Risk of SARS-CoV-2 infection reported in the world: despite of the little data available on 
incidence reports from China, The Netherlands and Madrid vary from 6 to 38.9 per 100 exposed 
health care workers. The high variability on the incidence is related to the develop of 
institutional outbreaks, thus establishing a latent risk in all hospital institutions in a pandemic 
scenario (7,44,76). To assess the sampling size calculation for this study, besides what has been 
reported internationally, an approximate calculation of the incidence of SARS-CoV-2 infection 
in the health care institutions in which the study will be held was performed. It is important to 
know the infection and epidemic control variates from one institution to another. While some 
actively screen asymptomatic health care personnel others only screen symptomatic health 
care personnel. The incidence observed in a 2-month period of time variates between 3.3% and 
13.7% with a mean of 11.2 cases per 100 health care workers.  
Based on that preliminary information, an expected risk for SARS-CoV-2 infection in the control 
group (Placebo + PPE) of 0.10 was used for the calculation. With the objective of estimating 
precisely a 50% relative risk reduction an assumption of an expected risk of 0.05 was done in 
the intervention group (Tenofovir/Emtricitabine + PPE) in order for a difference of 0.05 to detec 
between both groups.  
● Power: 0,80.  Alfa level: 0.05  
● Assignation ratio n1/n2= 1: 1 (randomization1: 1). 
● Sample size: 858 (429 per group). 
Considering possible loses up to 10% it is risen to 950 in total (with randomization 475 participants 
to each group). 
As a limitation of the study, if the incidence or the effect of the interventions are considerably lower 
than expected, the power to detect significant differences between both groups will be reduce. 
However, due to the progression of the pandemic in our country, with a tendency to increase, it is 
probable that the incidence observed in health care professionals will remain stable or even increase 
not only for the intrahospital risk, but for the risk in the community,   
3.5. 
Duration of the study and time of termination  
● Duration of the interventions:  60 days 
● Total duration of the Project: 8 months  
 2 months planning, 5 months collecting data, 2.5 months recruiting and a month for 
data analysis and publication.  

 
3.6. 
Procedures 
In table 1. Detailed follow up evaluations are described.   
Table 1. Description of the evaluations to be done during the trial.  
Follow up table 
Da
y 
General activity   
Specific activity 
Responsible 
Result  
 0 
Base line 
diagnoses  
Initial Clinical 
evaluation  
Medical doctor 
of the study 
Evaluating inclusion and 
exclusion criteria. 
Signing informed consent form  
Blood samples  
Nurse  
Lab tech 
Laboratory report: hemogram, 
creatinine, phosphorus, AST, 
ALT HIV ELISA, HB Surface 
antigen antibodies  
SARS-CoV-2 RT-PCR 
sampling  
 
Respiratory 
therapist or 
nurse  
Result of SARS-CoV-2 RT-PCR 
SARS-CoV-2 IgM and 
IgG antibodies 
Nurse  
Lab tech 
Result of IgM and IgG antibodies 
b-HCG sampling in 
women  
 
Nurse  
Lab tech 
Report of b-HCG 
 
20 
Visit 1 
Clinical evaluation 
Medical doctor 
of the study  
Clinical record and eCRF for 
clinical evaluation, adherence, 
and adverse events  

40 
Visit 2 
Blood sample for: 
SARS-CoV2 IgM, IgG 
antibodies and blood 
chemistry  
Nurse  
Lab tech  
Laboratory report of SARS-CoV2 
IgM, IgG antibodies and 
creatinine  
Clinical evaluation  
 
Medical doctor 
of the study  
Clinical record and eCRF for 
clinical evaluation, adherence, 
and adverse events  
60 
Visit 3 
Blood samples 
Nurse  
Lab tech 
hemogram, creatinine, 
phosphorus, AST, ALT HIV ELISA, 
HB Surface antigen antibodies b-
HCG in women 
SARS-CoV-2 RT-PCR 
sampling  
 
Respiratory 
therapist 
Result of SARS-CoV-2 RT-PCR 
Clinical evaluation  
 
Medical doctor 
of the study  
Clinical record and eCRF for 
clinical evaluation, adherence, 
and adverse events 
75 
Visit 4 
Blood samples 
Nurse  
Lab tech 
Laboratory report of SARS-CoV2  
IgG 
Clinical evaluation  
 
Medical doctor 
of the study  
Clinical record and eCRF for 
clinical evaluation, 
End of follow up and 
communication to 
study subject 
Clinical 
coordinator  
Minutes  
 
During follow up to any participant who develop COVID-19 related symptoms at any time after 
randomization given by two or more of the following: Body temperature higher than 38 Celsius, 
cough of recent onset (in the previous 10 days), dyspnea, odynophagia, malaise, fatigue, acute 
diarrheal disease, ageusia, dysgeusia, anosmia or hyposmia, an RT-PCR will be performed within 
the next 5 days and will be repeat it if the result is negative and the symptoms persist. This RT-PCR 
will be performed at every of the centers of the study and will request the patient the immediate 
report of the symptoms through an app or via phone call. In case of a positive RT-PCR the infection 

will be confirmed. While confirmation RT-PCR arrives, the participant will not quit taking the 
intervention. In that scenario, the intervention will only be suspended in the case of a highly 
suspected case or severe case requiring hospitalization.  
 
In case the infection is ruled out in the follow up, the participant will continue the interventions and 
follow up scheduled, according to graph 1.  
With regards to diagnostic testing during follow up as shown in table 1. IgG antibodies will be done 
at visit 2 and 4 (40 days from initially taking the intervention and 15 day after finalizing it). This 
considering volunteer that might acquire the infection in the last days of the pharmacological 
intervention. Moreover, at day 60, last of the intervention, an RT-PCR will be performed to all 
participants. This in order to detect participants who develop asymptomatic infection. The research 
group is aware that this follow up will not identify a 100% of the asymptomatic infection for the low 
sensitivity of testing in this scenario, approximately 30 to 40% (46,47), yet it will be done in both 
arms.   
Importantly, for the covid-19 emergency, clinical follow up, adverse event reporting and adherence 
reporting could be done online. 
Personal Protective Equipment  
All volunteers will be using the following personal protective equipment. This based on the 
guidelines of the WHO (23). See table 2.  
 
Table 2. Use of PPE by study volunteers. 
Area 
Health 
care 
personnel 
or 
patients 
Activity 
Type of PPE or activity 
Emergency room, 
general 
COVID 
wards or intensive 
care units 
Health 
care 
workers 
Direct contact with the 
patient of non-aerosol 
generating procedures.  
 
Surgical mask 
Visor or glasses. 
Long sleeve gown 
Nonsterile 
gloves. 
Direct contact with the 
patient 
and 
aerosol 
generating procedures.  
 
N95 respirator 
Visor or glasses. 
Long sleeve gown 
Nonsterile gloves. 
May 
dress 

under 
the 
robe that is 
removed at 
the end of 
the shift 
Other 
areas 
of 
transit 
(hallways 
or waiting 
rooms) 
 
All 
personnel 
including 
health 
care 
workers 
Any activity that does 
not involve contact 
shorter 
than 
2 
meters in distance 
between people  
Surgical mask  
Adapted from: Rational use of personal protective equipment for coronavirus disease 2019 (COVID-19). Interim guidance 
27 February 2020. World Health Organization. (23) 
*Health care worker: person in whose activity directly care a contact, suspected, or confirmed case of COVID-19.   
 
3.6.1. 
Informed consent and enrolling  
Volunteers Will be recruited at High complexity Health institutions that are part of the study. 
Through direct invitation either personal or by email. An information sheet for the participant Will 
be done (appendix 5. According to good clinical practice and considering eligibility criteria one of 
the investigators will perform the informed consent process explaining study objectives, potential 
benefit, and risks. After verifying understanding by the potential participant, the informed consent 
format will be signed according to current regulation.  
3.6.2. 
 Baseline evaluation 
The doctor assigned to the study takes a medical history that includes a review of systems, past 
medical history, and a complete physical examination. In addition, he or she will order laboratory 
exams described in Table 1. In case of clinical or laboratory alteration defined in the exclusion 
criteria, the volunteer will be excluded and will not continue in the following phases. Additionally, a 
RT-PCR will be carried out with a nasopharyngeal swab sample and a serological test of IgG antibody 
titers against SARS-CoV-2. In case of having any of the previously mentioned tests positive, the 
volunteer will be excluded. Female volunteers will undergo qualitative β-HCG and, if positive, they 
will be excluded or if they report the desire to become pregnant in the next two months. At 24 to 
48 hours with the results of the examinations and a new anamnesis the eligibility of the volunteer 
will be confirmed. If so, the randomization process will be carried out and the intervention will be 
delivered according to the process defined in the concealment section of allocation (3.6.4) and 
administration of the intervention product or placebo (3.6.5). 

 
3.6.3. 
 Randomization 
A simple randomization will be carried out, considering that it is not deemed necessary to stratify 
by any characteristics of the individuals, or by center. Additionally, due to the size of the sample 
there is little possibility of presenting a significant imbalance between the groups regarding 
characteristics that affect the outcome. 
The randomization will be carried out with a 1:1 relationship between the active intervention and 
the placebo, a randomization system generated by the REDCap software will be used, with random 
numbers that will meet the following requirements: each volunteer will have a known probability, 
and equal to be assigned to any of the interventions, future assignments will not be predictable 
based on previous assignments, the order of assignment will be reproducible. 
The randomization will be carried out centrally, by a trained member of the HUSI research office, 
who is not part of the research group, or the study staff, after generating the randomization, this 
will be communicated exclusively to the chemist central pharmacist of the research team. 
3.6.4. 
Allocation concealment 
Mechanisms will be applied to ensure concealment of randomization. The decision to include a 
volunteer in the study will be made without knowing the intervention that said individual will 
receive if they participate, that is, neither the investigators nor the study personnel will know the 
assignment before the start of the intervention. The following strategies will be used in the study to 
ensure this: 
- The randomization will be carried out centrally, the center that sends the volunteer to randomize 
at the central level, ensures that he meets all the eligibility criteria and registers the volunteer in the 
REDCap system, in such a way that it is impossible to subsequently change the allocation generated. 
- Prior to the start of recruitment, the central pharmaceutical chemist will mark 1000 bottles with 
labels with randomly assigned numerical codes, to the 500 bottles corresponding to TDF/FTC 
300/200mg and the other 500 bottles containing placebo. The only one who will know the 
information on the specific contents of the vials is the central pharmaceutical chemist of the study. 
- The person who will carry out the randomization process is not part of the research group or the 
research team, he will receive a notification by telephone and by REDCap, that there is a volunteer 
who is eligible to participate in the study. Through REDCap the random assignment will be 
generated, and the system will give you the code of the bottle that the volunteer should receive. 
This person will only inform the central pharmaceutical chemist, the code of the bottle that the 
subject must receive. 
- The central pharmaceutical chemist will communicate with the local pharmaceutical chemist, by 
means of a telephone call, and will inform him of the code of the bottle that must be given to each 
volunteer. The local pharmaceutical chemist will be blind to the intervention. 
- In REDCap a record will be kept of the selection of the study patient, as well as the fulfillment of 
the delivery of the bottle assigned by the program. 
 

3.6.5. 
Administration of the intervention product and placebo 
Volunteers assigned to the intervention group will receive one tablet of TDF/FTC 300/200mg each 
day. Each volunteer will be given 60 tablets of the medicine at the beginning of the treatment and 
its administration will be verified daily by sending a virtual survey, in which the subject answers if 
he took the intervention, plus a follow-up diary that will be given to the patient of Virtual or manual 
way for people without access, to write adverse events, as well as the hours of daily exposure to 
patients with suspected or diagnosed COVID 19 and adherence to personal protection elements. 
These data will be stored in an eCRF for clinical follow-up, adverse events, and adherence. 
Patients assigned to the control group will receive a placebo that will have the same appearance 
and size and will not have any active ingredients. Similarly, 60 placebos will be delivered from the 
start of treatment. 
The medicine must be stored at a temperature not exceeding 30 ° C and in an environment without 
excessive humidity in its authorized container and packaging. 
3.6.6. 
 Blind or masked evaluation 
To control for biases related to the measurement or evaluation of the study subjects, during the 
study, it will be ensured that the investigators and the volunteers are blind to the assigned 
intervention. 
To ensure that the volunteer is blind to the intervention, they will not be informed which 
intervention they are receiving (tenofovir / emtricitabine or placebo) and additionally a placebo with 
a taste and presentation similar to tenofovir / emtricitabine will be used, on the other hand, the 
vials In which both the active drug and the placebo will be packed, they will be the same and will 
only be differentiated by the numbers on the labels. 
The researcher will be blind throughout the volunteer's follow-up, and this will be ensured because 
a central randomization will be carried out, only the central pharmaceutical chemist will know the 
assignment and the researcher will only know the code of the drug that the patient receives, which 
is not decodable. 
Finally, the person in charge of data analysis will receive a database that will be downloaded from 
REDCap, in which there will be a code that will identify which of two different interventions a 
volunteer has received, but which will not allow identifying whether they correspond to 
tenofovir/emtricitabine or placebo. This coding will only be revealed when the analysis is complete. 
There is only one person independent of the analysts and the researchers, who knows the code. 
3.6.7. 
 Study variables 
The study variables are in Annex 3 with their respective conceptual and operational definitions. 
3.6.8. 
Sample processing and interpretation of laboratory tests. 
● RT-PCR: it will be processed in the HUSI clinical laboratory for the volunteers of the HUSI, the 
National University Hospital and the Samaritana Hospitals; The centers of the Colsanitas Group will 
perform the PCR in the Colsanitas group laboratory and the PCR of the San Jorge Hospital at the 

Technological University of Pereira according to the protocols used in each of these institutions, 
with internal and external quality controls, as well as technical endorsed by the National Institute of 
Health. The results will be sent within 24 hours after taking the sample to the doctors assigned to 
the study, who will inform the patient and carry out the pertinent follow-up. (See Annex 6. 
Diagnostic tests) 
● Serological tests for IgG antibodies will be processed in the HUSI clinical laboratory and the 
Colsanitas Group centers. The qualitative detection of IgG antibodies against SARS-CoV-2 will be 
carried out in human serum or whole blood obtained from the volunteers, using the 
immunochromatography test: Standard Q, SD Biosensor®. The antibodies present in the sample 
form a complex with the antigen labeled with colloidal gold (SARS-CoV-2 recombinant antigen), the 
complex progresses under the action of chromatography and combines with the coated antibody 
(mouse monoclonal antibody IgM / IgG anti-human) in the IgG line to form a complex and develop 
color, which is a positive result. When the sample does not contain the SARS-CoV-2 IgG antibody, 
the complex cannot form and a red band does not appear on the IgG line, which is a negative result. 
Regardless of whether either SARS-CoV-2 IgG or IgM antibodies are present in the sample, the gold-
labeled quality control antibody will bind to the coated antibody on line C to form a complex and 
develop color (line C ) to validate the test. For the study, only IgG antibody results will be considered, 
contemplating the high rate of false positives of IgM tests, especially in asymptomatic patients (66). 
● Blood samples will be taken by nurses or bacteriologists assigned to the study, who will store, 
label, and manage them following the SOPs (standard operating procedures) established in each 
participating center. Complete blood count, liver, kidney function, phosphorus, HIV- ELISA, HBsAg 
Ab tests will be processed following the SOPs of the clinical laboratories hired for this purpose. The 
results will be sent via institutional email to the physicians assigned to the study and in charge of 
monitoring each volunteer. Their interpretation will be carried out in accordance with the values 
established as normal by said laboratory, in conjunction with the criteria described in this protocol 
to graduate the severity of AE (See table 4). The results of the paraclinical tests will be interpreted 
by a doctor assigned to the study who decide on the volunteer's continuity in the study. 
3.6.9. 
Procedure in case of presenting the primary outcome 
If the volunteer, after the start of the study, has a positive result of RT-PCR or IgG for SARS CoV2, 
which confirms the infection by COVID 19, they will be contacted virtually or in person. During this 
intervention, the following actions will be carried out: 
- You will be given information about your result, and you will be instructed to contact your 
occupational risk and health insurer. 
- The presence of alarm signs (drowsiness, dyspnea, cyanosis) will be evaluated. In case of any of 
these symptoms are present, the patient will be instructed to attend the emergency service, to 
receive treatment in accordance with current national and institutional guidelines.  
- The volunteer will be instructed to suspend the intervention product, and the masking will be 
released. 
- National Public Health Surveillance System mandatory notification form will be filled out, the 
institution where the volunteer works will be informed, and the completed form will be sent. 

- The volunteer will be informed that telephone follow-up will be carried out every 5 days until the 
symptoms are resolved or a maximum of six weeks after the diagnosis of COVID 19. In case of 
presenting any alarm sign during the follow-up, the patient will be recommended to attend the 
emergency department.  
During the telephone follow-up, the volunteer's primary outcome (COVID 19 infection) will be 
classified as follows: asymptomatic, mild, moderate, or severe COVID. If the patient does not answer 
due to physical impossibility (e.g. intubation), communication with a companion or family member 
previously authorized by the patient will be sought. 
3.6.9 Study withdrawal criteria 
The following criteria should determine the immediate withdrawal of the volunteer from the study: 
● Grade 2 or greater kidney abnormalities at any time of follow-up. 
● Clinical indication to start a drug with significant interactions with TDF/FTC during the 
development of the study. 
● Presentation of any serious adverse event related to the intervention, defined by the physicians 
assigned to the study. 
● Any Adverse Event (AE) that determines that the volunteer wishes to interrupt the intervention. 
● That the volunteer voluntarily and for any reason decide to withdraw from the study. 
If any of the previously mentioned criteria are met, the doctor assigned to the study in charge of the 
follow-up will immediately inform the coordinator of their respective center. The report of all AE 
will be made by the principal investigator of each center, in accordance with the INVIMA regulations 
and taking into account the Standardized Operating Procedures (SOP) established by the study. 
In the event that the patient withdraws their consent, no additional monitoring will be possible. This 
situation will be reported immediately to the clinical monitor and monthly to the Institutional 
Research and Ethics Committee (CIEI). 
 
3.6.10. 
Follow-up of volunteers with a positive pregnancy test at the end of follow-up 
Despite the fact that TDF/FTC is a classification B drug in pregnancy, and its use is recommended as 
one of the antiretrovirals of choice in pregnant women with HIV (76), within this study it was defined 
to exclude pregnant women, or with the desire to become pregnant, to avoid exposure to this drug 
given its high placental transfer to the fetus. 
There is no evidence in humans of teratogenicity with TDF/FTC, however there is evidence in 
monkeys, at doses twice as high as the therapeutic doses in humans, of decreased fetal growth and 
reduced fetal bone porosity within two months of initiation of maternal therapy; Regarding human 
studies, there is no demonstrated relationship with low birth weight, but there are conflicting results 
on the outcome of growth in childhood (77). 

In a randomized, double-blind, placebo-controlled trial of PrEP in African women, Mugo NR, and 
colleagues (78) evaluated the effect of TDF/FTC on pregnancy for HIV-uninfected women. 
Differences in the incidence of pregnancy, delivery outcomes, and infant growth were not 
statistically different for women who received PrEP with TDF alone, or combination of FTC + TDF 
compared to placebo at conception. Considering that PrEP was discontinued when pregnancy was 
detected and that the confidence intervals for delivery outcomes were wide, the authors did not 
commit to making definitive statements about the safety of PrEP in the period of periconception 
(78) . 
For the above reasons, if any volunteer presents a pregnancy at the end of the intervention period, 
a specific Informed Consent Form will be filled out to carry out a follow-up during the pregnancy. 
4. Statistical analysis plan 
Initially, a descriptive analysis of the information will be made, and measures of central tendency 
and dispersion will be reported according to the type of variables. In this phase, the similarity 
between the groups of the experiment will be evaluated and it will be calculated if there are 
differences in the groups due to chance. 
Primary outcome 
Taking into account that this study is a pragmatic clinical experiment, which will evaluate 
effectiveness, an intention-to-treat analysis will be carried out, to solve the main objective, the 
proportion of incidence of SARS-CoV-2 infection in each group will be determined at the day 75 post-
randomization, estimated as the cumulative incidence of infection using the Kaplan Meier method. 
Exposure of interest: Prophylaxis with TDF/FTC plus EPP vs placebo plus EPP. 
Primary outcome: SARS CoV2 infection 
Zero follow-up time (registration time in the registry): the time that the volunteer is randomized to 
the study interventions. 
Follow-up time: All individuals have a follow-up until they present the primary outcome, or meet 
any of the withdrawal criteria, or up to 75 days after the zero follow-up time, if they do not present 
the outcome. 
Event: SARS-CoV-2 infection. 
Censorship: censorship occurs when the outcome is not presented, the two types of censorship will 
be: administrative censorship 75 days after randomization, or censorship for compliance with any 
of the criteria for withdrawal from the study, or loss of follow-up. 
The hazard ratio will be estimated by comparing the risk of infection in the intervention group 
(TDF/FTC + EPP), with the risk in the control group (placebo + EPP), with a confidence interval of 95 
%, using a univariate Cox regression model. 
If necessary, adjustment will be made for variables that may affect the occurrence of the primary 
outcome and that are not balanced between the intervention group and the placebo group; The 
need for adjustment with an OR greater than 1.5 will be considered for dichotomous categorical 

variables, such as sex; or if there are differences between the groups greater than 0.25 of the 
standard deviation for continuous variables such as age, adherence to pharmacological intervention 
or EPP, and hours of exposure to the COVID area. For the calculation of the adjusted hazard ratio, a 
multivariate Cox proportional hazards model will be used, if the proportionality assumption is met, 
or an extended Cox model if this assumption is not met. 
For secondary outcomes 
-The proportion of incidence of total adverse effects in each group will be determined at day 60 
after randomization, estimated as the cumulative incidence using the Kaplan Meier method. 
The hazard ratio (“Hazard Ratio”) will be estimated by comparing the risk of adverse events in the 
intervention group (TDF/FTC + EPP), with the risk in the control group (placebo + EPP), with a 
confidence interval of 95%, using a univariate Cox regression model. 
Additionally, the same analysis will be performed for serious adverse events. 
- The proportion of incidence of discontinuation of the intervention in each group, for any reason, 
will be determined at day 60 after randomization, estimated as the cumulative incidence using the 
Kaplan Meier method. 
The hazard ratio will be estimated by comparing the discontinuation of the intervention in the 
intervention group (TDF/FTC + EPP), with the risk in the control group (placebo + EPP), with a 
confidence interval of 95 %, using a univariate Cox regression model. 
- It will be determined as the difference in the mean or median (according to the distribution of the 
data) of the percentage in which the individuals were adherent 
-For the severity of the clinical course of the patients who develop the infection in both groups, a 
descriptive analysis will be carried out, the quantitative variables will be summarized by measures 
of central tendency and dispersion, according to the most appropriate measures for their 
distribution. The qualitative variables will be summarized by using absolute and relative frequencies 
(proportions) represented by percentages. 
4.1 Data and Security Surveillance Committee: 
A data and safety surveillance committee (DSSC) is defined as a group of experts, independent of 
the sponsor and investigators, who monitor the safety and validity of clinical trials. The committee 
carries out surveillance activities during established time intervals, in which, in addition to the safety 
data, the adequate recruitment of volunteers, compliance with the protocol, and the quality of the 
data obtained are evaluated (79). 
 A review of the literature by Sydes and colleagues (80) found that a DSSC is recommended when 
trials have any of the following characteristics: trials on high-profile topics that are a focus of 
community concern, to be used to search regulatory approval, or likely to profoundly affect clinical 
practice; trials with serious safety problems, unknown risks or that are implemented in vulnerable 
populations; and trials where independent monitoring is needed due to double-blind treatment 
allocation or long-term follow-up or because the sponsoring company does not have standard 
operating procedures. These authors also consider that DSSC may not be needed for trials of short 

duration (where it is not feasible to convene a DSSC in a timely manner to review the data), for trials 
with known risks that are minimal, for trials where the objective is to demonstrate biological 
principles (as in early phase clinical trials) or for trials on behavioral or administrative problems. 
In the case of this study, in favor of having a data and security monitoring committee, it is found 
that the issue addressed in the research is of high concern to society, given the importance of health 
workers for the management of people with COVID-19 infection, but also the implications that 
demonstrating the effectiveness of this intervention in this population may have, to later be able to 
demonstrate it in other populations such as the elderly or the general population. However, the 
difficulty of conducting a data monitoring committee in this experiment lies in its short duration, 
with a collection of information in only four months, which makes it impossible, a timely review of 
it, which allows making decisions before Upon completion of recruitment, on the other hand, 
TDF/FTC is not a new drug and there is extensive knowledge about its safety and tolerance, and 
based on this information, a large part of the inclusion and exclusion criteria of the present study 
have been included , therefore, frequent and serious safety problems are not expected (10-13) 
For this reason, it has been decided that this clinical experiment does not have a data monitoring 
committee, for the reasons previously stated. To avoid deviations in the protocol, there will be an 
investigator's manual, in which the management of serious and non-serious adverse events is 
explicit, as well as their causality analysis, and a set of standard operating procedures (SOPs). that 
will be delivered, disseminated and knowledge will be guaranteed by each of the participating 
centers during the enlistment process, strict monitoring by each of the monitors of the centers will 
also be guaranteed during recruitment, with internal audits and with minus one external audit 
before the third month of recruitment for each center, which will evaluate the conduct of the study, 
adequate recruitment of volunteers, compliance with the protocol, investigator's manual, SOPs, 
good clinical practice, and data quality. 
5. Risks and benefits for volunteers 
5.1 Risks for volunteers 
The risks for volunteers will be divided into those related to the pharmacological intervention. 
5.1.1 Risks potentially associated with pharmacological intervention 
TDF/FTC is considered a safe drug in the short term, and in periods of up to 2 to 3 years of use (81). 
In the studies of PrEP in HIV in which this drug is used as monotherapy, the systematic review by 
Fonner et al. (82) found no differences in the proportion of adverse events comparing TDF/FTC with 
placebo, in 10 randomized clinical trials (RCTs) controlled (OR 1.01, 95% CI 0.99 to 1.03, p = 0.27); It 
also found no differences in the subgroup analysis, according to adherence, gender, dose or age; 
nor in grade 3 or 4 adverse events when comparing the PrEP and placebo groups in 11 placebo-
controlled RCTs (risk ratio = 1.02, 95% CI 0.92-1.13, p = 0.76). 
The most common adverse effects reported with the drug are nausea, gastrointestinal (abdominal 
pain, bloating), and headache (77, 81). The use of TDF-FTC as PrEP has been associated with a mild 
non-progressive decrease in creatinine clearance (83), which is reversible on discontinuation of the 
drug (84). 

An association has also been described between a decrease in bone mineral density (BMD) and the 
use of FTC-TDF for 24 weeks (84-87), but no evidence of an increased risk of fractures has been 
found, on the other hand, change in BMD did not progress after 24 weeks of use and recovered to 
levels seen in the placebo arm after stopping TDF/FTC (88-89). 
Finally, there is a risk of severe acute exacerbations of hepatitis B in patients with hepatitis B virus 
(HBV) infection who discontinue TDF/FTC. Liver function should be closely monitored with clinical 
and laboratory follow-up for several months in HBV-infected patients who interrupt TDF/FTC, 
however, this phenomenon is rare, and the only evidence available is case reports. (90-92). In the 
present study, this risk will be avoided, because people with acute or chronic hepatitis B infection 
will be excluded and all volunteers will have immunity to hepatitis B, with anti-HBs greater than 10 
IU/ml. 
The following information presents, in more detail, the safety of TDF/FTC based on clinical, 
laboratory abnormalities, as well as alterations in bone mineralization and kidney function. 
- Experience based on clinical experiments 
Due to the control conditions of clinical trials, it is possible that the rates of adverse reactions that 
have been described do not necessarily reflect those observed in clinical practice and may be 
overestimated. 
Gallant JE et al. In a randomized clinical trial comparing efavirenz (EFV) plus TDF/FTC (N = 257) vs 
EFV  plus zidovudine (AZT) / lamivudine (3TC) (N = 254) for the management of HIV infection in 511 
Subjects over 18 years of age, for 144 weeks, reported the following adverse reactions: dizziness 
(8%), diarrhea (7%), nausea (8%), fatigue (7%), headache (5%), depression ( 4%), insomnia (4%), skin 
rash (5%) (93). 
Reported laboratory abnormalities included: amylase greater than or equal to 132 (17%), 
triglycerides greater than 400 mg / dL (13%), neutrophils less than 1000 (7%), hematuria (9%), AST 
greater than 109 in men or 86 in women (8%), ALT greater than 91IU / L in men or 86 IU / mL in 
women (7%) (93). However, in this study TDF/FTC was accompanied by EFV, which explains several 
of the adverse effects, especially psychiatric ones, and skin rash. 
More recently, the safety and risk profile of TDF/FTC adverse reactions has been studied in clinical 
studies of HIV pre-exposure prophylaxis (PrEP) in monotherapy. Grohskopf A. et al. Conducted a 
clinical experiment to evaluate the safety of a daily dose of TDF in HIV-uninfected subjects for 24 
months. The study drug was initiated by 373 (93%) volunteers (186 TDF and 187 placebo), of whom 
325 (87%) completed the final study visit. Of 2428 adverse effects (AE) reported among 334 (90%) 
volunteers, 2366 (97%) were of mild or moderate severity. The frequencies of commonly reported 
AE did not differ significantly between the TDF and placebo arms. In multivariate analyzes, back pain 
was more likely among TDF recipients (P = 0.04), these reports were not associated with 
documented fractures or other objective findings. There was no grade ≥3 creatinine elevations, and 
grade 1 and 2 creatinine elevation were not associated with TDF reception. The estimated 
percentage of adherence was 92% per pill count. (94). 
The Partners PrEP study recruited 4,758 couples, of which 4,747 were followed, 1,584 randomly 
assigned to TDF, 1,579 to TDF-FTC, and 1,584 to placebo. The rate of serious adverse events at 36 

months of follow-up was similar in all study groups. There were no statistically significant differences 
in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus 
abnormalities in the study arms. Neutropenia was seen more frequently in the TDF/FTC arm (15% 
with a grade 1 or 2 event, 4% with a grade 3 or 4 event), but not in the TDF arm (12% with a grade 
1/2 , 2% grade 3/4), compared to placebo (12% grade 1/2, 2% grade 3/4). The study medication was 
well tolerated, with a moderate increase in reports of gastrointestinal side effects and fatigue in the 
two active arms compared to the placebo arm, mainly during the first month of administration 
(77,95) 
Retention was 96% or greater during the study period. Study medication interruptions for safety-
related reasons accounted for less than 1% of the total follow-up time: 0.6% in the TDF group, 0.7% 
in the TDF-FTC group, and 0.6% in the placebo group. (77.95) 
The iPrEX study enrolled 1603 volunteers, of whom 1,225 chose to take PrEP. Reported symptoms 
peaked in the first month, with 39% potentially related to PrEP compared to 22% at baseline. 
Symptoms largely resolved within 3 months. Symptoms related to the digestive tract in the first 4 
weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI 0.23 to 0.96). Reports 
of gastrointestinal symptoms were associated with 7% (95% CI, 4% -11%) of suboptimal adherence 
in this cohort (96). 
In this study, PrEP delivery was discontinued during the study in 56 (5%) volunteers due to "adverse 
effects." The study volunteer or medical staff could initiate interruptions. The interruption was 
temporary for 22 volunteers, the combined duration of these temporary interruptions totaled 10 
person-years, a reduction of 0.6% (10 person-years from a possible 1784 person-years) in the total 
possible person-years. The discontinuation was permanent for 34 volunteers and decreased the 
total possible use of PrEP in 35 person years, 2.9% of the possible use in the cohort. The most 
common adverse effects cited for non-dispensing were nausea, abdominal pain (0.9% possible use), 
diarrhea (0.4%), and skin problems / itching, pain in head and flatulence (0.3% each (96). 
 
- Laboratory abnormalities 
Grade 2 to 4 laboratory abnormalities seen in the iPrEx and Partners PrEP assays are rare, generally 
less than 5% (80-82). Six subjects in the TDF-containing arms of the Partners PrEP trial discontinued 
the trial due to an increase in serum creatinine, compared with no discontinuation in the placebo 
group. One subject in the TDF/FTC arm of the iPrEx trial discontinued due to an increase in serum 
creatinine and another subject discontinued due to low serum phosphorus. Grades 2-3 proteinuria 
(2-4 +) and / or glycosuria (3+) occurred in less than 1% of TDF/FTC-treated subjects in the iPrEx trial 
and the Partners PrEP trial. 
 
- Alterations in bone mineralization. 
In some clinical trials evaluating TDF/FTC in pre-exposure prophylaxis for HIV for 18 months, 
decreases in bone mineral density (BMD) have been observed and described in uninfected 
individuals. In the iPrEx trial, a substudy of 503 subjects found mean changes from baseline in BMD 

ranging from –0.4% to –1.0% in total hip, spine, femoral neck, and trochanter in the TDF/FTC group 
compared to the placebo group, who returned to their baseline values after PrEP was discontinued. 
13% of TDF/FTC treated subjects, in contrast to 6% of placebo treated subjects, lost at least 5% of 
BMD in the spine during treatment. Bone fractures were reported in 1.7% of the TDF/FTC group 
compared to 1.4% in the placebo group, however, no correlation was observed between BMD and 
fractures. (96) 
The Partners PrEP trial found similar fracture rates between the treatment and placebo groups (0.8% 
and 0.6%, respectively); BMD was not assessed in this trial (81). Liu AY, et al. In 2011 evaluated the 
prevalence of low BMD using dual energy X-ray absorptiometry (DEXA), in a baseline cohort of 210 
HIV-uninfected men who have sex with men (MSM) who underwent a randomized clinical trial of 
daily TDF versus placebo. At baseline, 20 volunteers (10%) had low BMD (Z score ≤ 2.0 at L2-L4 spine, 
total hip, or femoral neck). Low BMD was associated with the use of amphetamines (OR = 5.86, 95% 
CI 1.70-20.20) and inhalants (OR = 4.57, 95% CI 1.32-15.81); there was a 1.1% net decrease in mean 
BMD in the TDF group versus the pretreatment / placebo group in the femoral neck (95% CI 0.4-
1.9%), 0.8% net decrease in the total hip (95% CI 0.3-1.3%) and 0.7% in column L2-L4 (95% CI -0.1-
1.5%). At 24 months, 13% vs. 6% of volunteers experienced more than 5% loss of BMD at the femoral 
neck in the TDF versus placebo groups, however these associations were not statistically significant 
(p = 0.13) (87) 
Kasonde M, et al. Evaluated the effect on bone mineral density of daily TDF/FTC use compared to 
placebo among heterosexual men and women aged 18 to 29 years enrolled in the Botswana TDF2 
PrEP study. Volunteers had BMD measurements at baseline and then every 6 months with dual-
energy X-ray absorptiometry (DEXA) performed on the hip, spine, and forearm. A total of 220 
volunteers (108 TDF-FTC, 112 placebo) had baseline BMD measurements at all three anatomical 
sites; 15 (6.8%) of the volunteers had a low BMD level at baseline (z-score <-2.0 at each anatomical 
site) including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02) (97). 
Low baseline BMD was associated with low weight (p = 0.02), high blood urea nitrogen content (p = 
0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses> 
3.0% at any anatomical site at any time after study initiation were significantly greater for the TDF-
FTC treatment group [34/68 (50.0%) versus 26/79 (32.9%) placebo (p = 0.04). There was a small but 
significant difference in mean percentage change in BMD from baseline for TDF/FTC versus placebo 
at all three sites at month 30 [forearm -0.84% (p = 0.01), column -1.62% (p = 0.0002), hip -1.51% (p 
= 0.003). In conclusion, the use of TDF-FTC was associated with a small but statistically significant 
decrease in BMD in the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy young 
adults in Botswana had an abnormal baseline BMD. This association is in relation to the time of 
exposure to TDF/FTC. (97). 
- TDF/FTC and kidney function 
Tenofovir-associated nephrotoxicity encompasses a spectrum of manifestations including proximal 
tubular dysfunction, acute kidney injury, CKD, and nephrogenic diabetes insipidus. Proximal tubular 
dysfunction is the main one among them, it has to do with the depletion of mitochondrial DNA 
mediated by the accumulation of drugs within the proximal renal tubules. Proximal tubular 
dysfunction can rarely progress to Fanconi syndrome, a complete tubulopathy that includes 

metabolic acidosis and bone disorders and occurs in 0.3 to 2% of people who take this drug 
chronically (98,99) 
In patients with human immunodeficiency virus infection, it has been recommended to avoid the 
use of tenofovir when the glomerular filtration rate (GFR) is less than 60 mL / minute / 1.73 m2, this 
is a strong recommendation in favor made by IDSA ( Infectious Diseases Society of America). 
Likewise, in patients in whom a decrease in GFR greater than 25% from baseline or when it is less 
than 60 mL / minute / 1.73 m2 has been confirmed, it is recommended to replace tenofovir, 
especially when there is evidence of proximal tubular dysfunction. (100) 
Tenofovir has been infrequently associated with renal dysfunction due to tubular necrosis. Herlitz 
LC, et al., described 13 cases of tenofovir-associated nephrotoxicity: 6 women and 7 men with a 
mean age of 51.1 ± 9.6 years. Patients were treated with tenofovir for a mean of 19.6 months. Nine 
patients had acute kidney injury and 4 had mild kidney failure with sub nephrotic proteinuria. The 
mean serum creatinine was 1.3 ± 0.3 mg/dl, increasing to 5.7 ± 4.0 mg/dl at the time of the biopsy. 
Renal biopsy revealed acute toxic tubular necrosis. Clinical follow-up after tenofovir discontinuation 
averaged 13.6 months in 11 of the 13 patients. Recovery of kidney function occurred in all patients, 
including 4 who required temporary hemodialysis. The study showed that tenofovir disoproxil can 
lead to a form of reversible acute tubular necrosis. (101) 
This effect in the reduction of GFR with the use of tenofovir seems to be related to the time of 
exposure to the drug and behaves as a reversible toxic damage, for which the timely withdrawal of 
the drug is indicated (102). During the clinical experiment, the intervention with tenofovir disoproxil 
is planned to be administered for 60 days, for which we estimate that this nephrotoxic effect will be 
very infrequent. 
Cooper RD et al., In a systematic review and meta-analysis of 17 studies that included 9 randomized 
clinical trials and 7 prospective observational cohorts found that tenofovir was associated with 
lower creatinine clearance (averaging -3.9 ml / minute ) compared to regimens without tenofovir 
(103). The studies included in the meta-analysis had a median follow-up of 48 weeks, and subjects 
with a GFR <50 or <60 ml/min/1.73 m2 were excluded in 11 of them (102, 103). 
 
Post marketing experience 
Multiple adverse reactions have been described during post-approval use of TDF. No additional 
adverse reactions have been identified during use after FTC approval. These reactions are voluntarily 
reported by a population of uncertain size; Therefore, it is not always possible to establish causal 
relationships with drug exposure. 
Among the adverse reactions that have been reported for TDF during surveillance are: 
 
o Immune system disorders: allergic reaction, including angioedema. 
o Metabolism and nutrition disorders: lactic acidosis, hypokalemia, hypophosphatemia. 
o Respiratory, thoracic, and mediastinal disorders: dyspnea 

o Gastrointestinal disorders: pancreatitis, increased amylase, abdominal pain. 
o Hepatobiliary disorders: hepatic steatosis, hepatitis, increased liver enzymes (most commonly 
AST, ALT) 
o Skin and subcutaneous tissue disorders: rash 
o Musculoskeletal and connective tissue disorders: rhabdomyolysis, osteomalacia (manifested as 
bone pain and may contribute to fractures), muscle weakness, myopathy. 
o Renal and urinary disorders: acute renal failure, renal failure, acute tubular necrosis, Fanconi 
syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic 
diabetes insipidus, renal failure, increased creatinine, proteinuria, polyuria. 
Most of the adverse events as described are mild and infrequent. Severe events are much rarer and 
most of them are dose dependent and occur with prolonged use of the drug. During the present 
study, the intervention time is short, which minimizes the risk of adverse events dependent on the 
prolonged use of TDF. 
 
5.1.2 Potential risks not associated with pharmacological intervention 
Volunteers are potentially exposed to the risks inherent in taking any blood sample such as: 
● Pain at the puncture site. 
● Extravasation or bruising. 
● Peripheral nerve injury (Very rare). 
● Infection (Very rare). 
● Anxiety. 
All these risks will be mitigated by using established and validated protocols in each of the 
participating institutions, taking timely paraclinical tests, and constant supervision of the study by 
qualified personnel trained in the study procedures. 
5.2 Benefit for volunteers 
The study is based on previously reported findings in the scientific literature regarding the potential 
ability of tenofovir disoproxil/emtricitabine to inhibit SARS-CoV-2 replication (13, 47–50). Therefore, 
volunteers could benefit from the reduced risk of developing COVID-19 which could mean a 
decreased risk of developing symptoms, temporary disability, hospitalization, transmission to family 
members and close contacts, and to other members of the community. Among the possible 
complications associated with COVID-19, it could reduce the severity or risk of mortality during the 
follow-up period. Additionally, the continuous and accessible use of EPP for the study volunteers 
reduces the risk of contagion by COVID-19. The findings of the present study could lead to a change 
in public policies that in the future will reduce the risk of acquiring COVID-19 by health personnel. 
In accordance with current Colombian regulations, volunteers will not receive any type of financial 
compensation for their participation in the study. 

6. Report of adverse events 
6.1. Definitions 
● Adverse event (AE) 
Any adverse medical occurrence in a patient or subject of a clinical investigation to whom a 
pharmaceutical product was administered and that does not necessarily have a causal relationship 
with this treatment. Therefore, an adverse event (AE) can be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom or illness temporarily associated with the use 
of a medicinal (research) product, whether it is related. (104). 
Considering the above, the United States National Institute of Health in conjunction with the 
National Cancer Institute of the same country published standardized definitions of adverse events 
known as Common Terminology Criteria for Adverse Events (CTCAE). Events, for its acronym in 
English), to describe the severity of the organic damage caused to patients by the various 
medications (104,105). According to them, the following events are considered: 
● Serious adverse event (SAE) 
Any unfavorable occurrence than at any dose that: 
 Results in death. 
 Is life threatening, requires hospitalization of the patient or prolongation of existing 
hospitalization. 
 Results in persistent or significant disability / disability. 
 Generates a congenital anomaly / birth defect. 
● Fatal Serious Adverse Event. 
EAS that end in the death of the subject or threaten the life of the same. 
● Expected / Listed Serious Adverse Event. 
EAS whose specificity or severity is consistent with that described in the Research Protocol, 
Investigator's Manual / basic prescription information or product label. 
● Unexpected / Unlisted Serious Adverse Event. 
EAS whose specificity or severity is not consistent with that described in the Research Protocol, 
Investigator's Manual / basic prescription information or product label. 
● Non-Serious adverse event 
All other events that do not meet any of the EAS seriousness criteria 
● Adverse event requested 
They are the AE that will be searched for in each assessment of the subjects participating in the 
study. 
● Unsolicited adverse events 

They are the AEs that are voluntarily manifested by the patient that may or may not be related to 
the study drug. 
 
6.2. Assessment and documentation of adverse events. 
The researcher assigned to follow up the study subjects will be responsible for recording all adverse 
events in each participating institution, regardless of the group evaluated, with the following 
exceptions: 
A case report form will be created which must have the following information: 
● Description of the adverse event 
● Date of presentation, duration, and day of resolution. 
● Severity according to degrees mentioned 
● Conduct taken (need for treatment, suspension of medication, hospitalization) 
● The probability of relationship with the drug under study. 
All the follow-up of adverse events will be determined according to the Standardized Operational 
Plan for adverse events of the study. 
 
6.3. Degree of severity 
If the definition is met, the degree of severity of adverse events will be categorized. The 
categorization is found in Table 4 and is based on the (CTCAE) (104,105). According to them and the 
medicine used, the following events are considered: 
Table 4. Adverse event’s degree of severity  
CTCAE Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
Grade 5    
Nervous system disorders 
Headache 
Mild pain 
Moderate pain; 
limiting 
instrumental 
ADL 
Severe pain; 
limiting self-
care ADL 
 - 
 - 
Insomnia 
Mild difficulty 
falling asleep, 
staying asleep 
or waking up 
early 
Moderate 
difficulty falling 
asleep, staying 
asleep or 
waking up early 
Severe 
difficulty in 
falling asleep, 
staying asleep 
or waking up 
early 
 - 
 - 
Gastrointestinal disorders 

Abdominal 
pain 
Mild pain 
Moderate pain; 
limiting 
instrumental 
ADL 
Severe pain; 
limiting self-
care ADL 
 - 
 
Nausea 
Loss of 
appetite 
without 
alteration in 
eating habits 
Oral intake 
decreased 
without 
significant 
weight loss, 
dehydration, or 
malnutrition 
Inadequate 
oral caloric or 
fluid intake; 
tube feeding, 
TPN, or 
hospitalization 
indicated 
 - 
 - 
Vomiting 
Intervention 
not indicated 
Outpatient IV 
hydration; 
medical 
intervention 
indicated 
Tube feeding, 
TPN, or 
hospitalization 
indicated 
Life-
threatening 
consequenc
es 
Death 
Flatulence 
Mild 
symptoms: 
intervention 
not indicated 
Moderate; 
persistent; 
psychosocial 
sequelae 
 - 
 - 
 - 
Skin and subcutaneous tissue disorders 
Rash 
maculo-
papular 
Macules/papul
es covering 
<10% BSA with 
or without 
symptoms 
(e.g., pruritus, 
burning, 
tightness) 
Macules/papule
s covering 10 - 
30% BSA with or 
without 
symptoms (e.g., 
pruritus, 
burning, 
tightness); 
limiting 
instrumental 
ADL; rash 
covering > 30% 
BSA with or 
without mild 
symptoms 
Macules/papul
es covering 
>30% BSA with 
moderate or 
severe 
symptoms; 
limiting self-
care ADL 
 - 
 - 
Stevens-
Johnson 
syndrome 
 - 
 - 
Skin sloughing 
covering <10% 
BSA with 
associated 
signs (e.g., 
Skin 
sloughing 
covering 10 - 
30% BSA 
with 
Death 

erythema, 
purpura, 
epidermal 
detachment, 
and mucous 
membrane 
detachment) 
associated 
signs (e.g., 
erythema, 
purpura, 
epidermal 
detachment, 
and mucous 
membrane 
detachment) 
Allergic 
reaction 
Systemic 
intervention 
not indicated 
Oral 
intervention 
indicated 
Bronchospasm
: 
hospitalization 
indicated for 
clinical 
sequelae; 
intravenous 
intervention 
indicated 
Life-
threatening 
consequenc
es: urgent 
intervention 
indicated 
Death 
 
Table 5. Tables for Laboratory Abnormalities 
Laboratory 
abnormality 
Mild 
(Grade 1) 
** 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life 
Threatening 
(Grade 4) 
Death 
(Grade 
5) 
Laboratory 
ALT and AST 
>3 x ULN if 
baseline was 
normal. 1.5-3 
x ULN of 
baseline if it 
was not 
normal.  
>3-5 x ULN 
ULN if 
baseline was 
normal. >3-5 
x ULN of 
baseline if it 
was not 
normal. 
>5-20 x ULN 
if baseline 
was normal. 
>5-20 x ULN 
of baseline if 
it was not 
normal. 
>20 x LSN ULN 
if baseline was 
normal. >20 x 
ULN of 
baseline if it 
was not 
normal. 
 
Hemoconcentration 
Rise of 0-2 
g/dl from 
baseline. 
Rise of 2-4 
g/dl from 
baseline. 
Rise of > 4 
g/dl from 
baseline. 
 
 
Anemia  
Hb<ULN-
10g/dl 
Hb<10-8g/dl 
Hb<8g/dl 
Life 
Threatening; 
Medical 
Death   

intervention is 
required.   
Lymphocytes 
Decrease - 
cell/mm3 
< 800/mm3; 
< ULN - 0.8 x 
10e9/L  
<800 - 
500/mm3; 
<0.8 - 0.5 x 
10e9 /L  
<500 - 
200/mm3; 
<0.5 - 0.2 x 
10e9 /L  
<200/mm3; 
<0.2 x 10e9 /L  
 
Neutrophils 
Decrease - 
cell/mm3 
<LLN - 
1500/mm3; 
<LIN - 1.5 x 
10e9 /L  
<1500 - 
1000/mm3; 
<1.5 - 1.0 x 
10e9 /L  
<1000 - 
500/mm3; 
<1.0 - 0.5 x 
10e9 /L  
<500/mm3; 
<0.5 x 10e9 /L  
 
Platelets 
Decreased - 
cell/mm3 
<LLN - 
75,000/mm3; 
<LLN - 75.0 x 
10e9 /L  
<75,000 - 
50,000/mm3; 
<75.0 - 50.0 x 
10e9 /L  
<50,000 - 
25,000/mm3; 
<50.0 - 25.0 x 
10e9 /L  
<25,000/mm3; 
<25.0 x 10e9  
 
Creatinine – 
mg/dL 
Rise of 1.5x 
ULN  
Rise of 1.5 – 
3x from 
baseline; 1.5 
– 3 x ULN  
Rise of 3x 
ULN from 
baseline.; 3 – 
6 x ULN 
Rise of 6x ULN  
 ULN: Upper limit of normal range. LLN: Lower limit of the normal range.  
 
Table 5. Causation of adverse events. Taken from the Common Terminology Criteria for Adverse 
Events (104,105). 
Imputed 
causation 
Definition 
Definitive  
A clinical event, or alterations in laboratory tests, that manifests with a 
plausible temporal sequence in relation to the administration of the drug, and 
that cannot be explained by the concurrent disease, or by other drugs or 
substances. The response to drug withdrawal (withdrawal; dechallenge) must 
be clinically plausible. The event must be definitive from a pharmacological or 
phenomenological point of view, with a conclusive re-exposure (rechallenge). 
Probable  
A clinical event, or alterations in laboratory tests, that manifests with a 
reasonable time sequence in relation to the administration of the drug, that 
is unlikely to be attributed to the concurrent disease, or to other drugs or 
substances, and that when withdrawing the drug presents a clinically 
reasonable response. Information on re-exposure is not required to assign this 
definition. 

Possible 
A clinical event, or alterations in laboratory tests, that manifests with a 
reasonable time sequence in relation to the administration of the drug, but 
that can also be explained by the concurrent disease, or by other drugs or 
substances. Information regarding the withdrawal of the drug may be missing 
or unclear. 
Improbable 
 
A clinical event, or alterations in laboratory tests, that manifests with an 
unlikely time sequence in relation to the administration of the drug, and that 
can be more plausibly explained by the concurrent disease, or by other drugs 
or substances. 
Conditional / 
Not classifiable 
A clinical event, or laboratory test abnormalities, reported as an adverse 
reaction, for which more data is required to make a proper evaluation, or 
additional data is under review. 
Not assessable 
/ Unclassifiable 
A notification that suggests an adverse reaction but cannot be judged because 
the information is insufficient or contradictory, and that cannot be verified or 
completed in your data. 
 
7. Ethical considerations 
This research is considered to have a risk greater than the minimum, since it is a clinical experiment 
in which a pharmacological intervention will be carried out, according to Resolution 8430 of 1993. 
Therefore, there may be modifications in the biological variables, and adverse effects from the 
intervention could occur. 
This research will be presented to the Research and Ethics Committee of the Hospital Universitario 
San Ignacio and the Pontificia Universidad Javeriana, and to the ethics committees of the 
participating institutions for approval. Attached to this document, the informed consent forms 
(Annex 4), as well as the corresponding annexes, will be presented. These documents will be 
thoroughly evaluated and approved when the committee considers that they meet the necessary 
quality and ethical standards. 
To obtain the data, an in-depth explanation of the informed consent will be made to the volunteers 
in individual sessions. Additionally, the volunteer will be explained the days of clinical follow-up, the 
possible adverse effects of the intervention, any doubts that may arise will be resolved and it will 
be made clear to them that they are free to participate or not in the study and that they can be 
withdrawn at any time. moment. 
● Privacy and confidentiality 
It will seek to respect privacy, confidentiality and promote the rights and well-being of all the 
subjects involved in this research defined in article 5 of this same resolution. Additionally, under the 
support of statutory law 1581 of 2012 "Habeas data", approval will be requested for the handling 
of personal data in the informed consent. It will be guaranteed that their identification is not taken 
within the variables to be analyzed in the study, and that, at the time of information analysis, the 
database is anonymized (each volunteer will have an assignment code that will not be decipherable), 

respecting the this way the confidentiality and privacy of the data of each volunteer who is part of 
the study. 
All the data of the study volunteers will be kept in a password-protected database and stored 
according to the information management protocols for research purposes of the Hospital 
Universitario San Ignacio and the other participating centers. Volunteers will not be able to access 
their personal information related to the study. 
The database will be known to the principal investigators and will be stored during the study on 
their computer (s). Researchers will have access for data analysis through a storage platform called 
"RedCap". This platform complies with the transfer law. Upon completion of the study, a copy of 
the information will be made, and it will be stored on magnetic media and deleted from the work 
computer (s). The study information will be stored for up to 5 years after this. 
● Conflicts of interest 
The researchers declare that they have no conflicts of interest. However, if this changes, conflicts of 
interest will be declared for each researcher. In Annex 7. The conflicts of interest of each of the 
researchers are presented during the development of the research protocol. 
● Policy of publication and dissemination of results 
No personal information that can identify the study subjects will be disclosed when the research 
results are published. A report will be prepared with the conclusions of the study to present in the 
academic-scientific spaces of the San Ignacio University Hospital, the participating centers and in 
national and international scientific academic events. Additionally, two manuscripts will be 
prepared for publication in a journal of national or international biomedical interest. The first 
manuscript about the main results of the study and the second about the description of the kinetics 
of diagnostic tests in the clinical experiment. 
The decision about the order of the authors will be determined by the scientific committee of the 
experiment, which will be made up of one person from each of the participating institutions. 
● Completion of the study 
The Research and Ethics Committee of the Hospital Universitario San Ignacio and the Pontificia 
Universidad Javeriana, may decide to terminate the study at any time with prior notice to the 
researchers and co-investigators. 
● Insurance policy for clinical trials 
This study will have an insurance policy for volunteers in clinical trials that complies with article 13 
of Resolution 8430 of 1993 of the Ministry of Health of Colombia. This policy will be taken for a value 
of COP $ 70,000,000 MCTE and will cover the probable adverse events caused by the intervention 
that the volunteers may present. 
The policyholder is the Pontificia Universidad Javeriana, and this has been preliminarily contracted 
with the Previsora, Insurance company. Headquarters Address: Calle 57 # 9 -07. PBX: +571 348 5757 
/ Postal Code 52946. 

 
 
 
 
 
 
 
Table 6. Study schedule 
 
 
 
 
 
 
 
 
WORK PLAN AND SCHEDULE 
Timetable 
 
Prepara
tion 
and 
logistics 
Recruit
ment 
Follow up 
Results 
Data 
analysi
s 
Communica
tion and 
publication 
 
Months 
1-2 
3-5 
Visits 
5-7 
8 
8 
Activities 
 
 
1 2 
3 4 
 
Product 
Deliverable 
result 
Documentary 
enlistment of 
procedures 
X 
 
 
 
 
 
 
 
 
Standard 
Operating 
Procedures 
and 
Investigator 
Manual 
SOP protocol 
documents and 
Investigator 
Manual 
Acquisition of 
supplies and 
equipment 
X 
 
 
 
 
 
 
 
 
Diagnostic 
test kits, 
PPEs, 
computers, 
tablets 
Inventories, 
purchase 
orders, invoices 
CRF design 
X 
 
 
 
 
 
 
 
 
Data 
extraction 
form 
CRF registration 
number - 
Certificate 

Training and 
opening of 
centers 
X 
 
 
 
 
 
 
 
 
GCP courses 
carried out in 
centers, Visits 
to study 
centers 
Minutes - GCP 
course approval 
certificates 
Telephone 
contact 
potential 
volunteers 
 
X 
 
 
 
 
 
 
 
Registration 
with 
participants 
interested in 
being 
included 
Record of 
execution of the 
procedure and 
database in 
Excel. 
Informed 
consent 
 
X 
 
 
 
 
 
 
 
Signed 
informed 
consents 
Database of 
study subjects 
recruited 
Clinical CRF 
history 
 
X 
X X 
X X 
 
 
 
Clinical 
History of the 
study subject 
Clinical CRF 
Registry 
Clinical 
Assessment 
 
X 
X X 
X X 
 
 
 
Clinical 
History of the 
study subject 
Clinical CRF 
Registry 
Supervised 
first dose of 
drug 
administratio
n 
 
x 
 
 
 
 
 
 
 
Confirmation 
of taking at 
least 1 dose 
of TDF/FTC or 
placebo 
Drug dispensing 
registration 
document 
Taking of RT-
PCR for SARS-
CoV-2 
 
X 
 
 
X 
 
 
 
 
Positive or 
negative 
diagnostic 
test result 
Laboratory 
report 
Antibody IgG 
- IgM SARS - 
CoV-2 testing 
 
X 
 
x 
 
x 
 
 
 
Positive or 
negative 
diagnostic 
test result 
Laboratory 
report 
Sampling for 
CBC, 
Creatinine, 
AST, ALT, P, 
HIV ELISA, 
Acs anti 
HBsAg and 
 
X 
 
X 
 
X 
 
 
 
Results of 
liver, kidney, 
hematologica
l, electrolyte 
function tests 
and 
pregnancy 
status in the 
Laboratory 
report 

Beta HCG in 
women 
case of 
participating 
women. 
Verification 
of eligibility 
criteria 
 
X 
 
 
 
 
 
 
 
Determinatio
n of the 
inclusion or 
not of the 
participant 
Check list 
Randomizatio
n 
 
X 
 
 
 
 
 
 
 
Random 
Assignments 
to 
Intervention 
or Placebo 
Database 
CRF Adverse 
Events 
Registry 
 
 
X X 
X X 
 
 
 
History of 
adverse 
events 
CRF registration 
document 
Adverse event 
Finish follow-
up and 
communicati
on to the 
study subject 
 
 
 
 
 
 
X 
 
 
Formal 
follow-up 
completion 
record 
Completion 
certificate 
document 
Systematizati
on and 
organization 
of data 
 
 
 
 
 
 
X 
 
 
Office registry 
refined with 
data 
extracted 
from the 
clinical trial 
Systematized 
database 
Results 
analysis 
 
 
 
 
 
 
 
X 
 
Outcome 
estimates, 
statistical 
associations, 
causality 
inferences 
and risks of 
bias and 
limitations 
Document with 
results, tables, 
graphs and data 
of the study 
Communicati
on and 
publication of 
results and 
conclusions. 
 
 
 
 
 
 
 
 
X 
National and 
international 
communicati
on of the 
results and 
Two articles of 
scientific 
publication, 
report of results 
and 
recommendatio

conclusions 
of the study 
ns of the 
researchers 
 
9. 
Budget  
  
9.1 Technical services  
  
No.  
  Item  
Site  
Justification  
Quantity  
Unit value  
(cop)  
Subtotal  
(cop)  
1  
Civil liability policy for 
volunteers and clinical trial 
personnel  
Pontificia  
Universidad  
Javeriana  
Regulatory agency 
requires a liability 
protection for 
both, volunteers and 
clinical 
trial personnel regarding 
risks during COVID-19 
pandemic.  
1  
 $           96,101,872.44    $           96,101,872.44   
2  
Clinical laboratory 
tests (Creatinine; CBC; ALT; 
AST; 
BHCG in women, antiHBS; HIV, 
IgG Antibodies; Serum 
phosphorus, CRP)  
Pontificia  
Universidad  
Javeriana  
Laboratory exams required 
at baseline and follow-up  
1  
 $         535,959,372.00    $         535,959,372.00   
3  
rtPCR for symptomatic 
volunteers (7,5%)  
Pontificia  
Universidad  
Javeriana  
rtPCR for follow-up 1, for 
volunteers who develop 
respiratory symptoms 
(estimated of 7.5%)  
71  
 $                250,000.00    $           17,750,000.00   
4  
  
Laboratories for follow-up 
2 (creatinine and antibodies)  
Pontificia  
Universidad  
Javeriana  
Laboratory 
tests for 950 volunteers  
1  
 $           50,071,650.00    $           50,071,650.00   
5  
RtPCR including transport 
media for follow-up 2.  
Pontificia  
Universidad  
Javeriana  
Laboratory tests.  It is 
estimated that 7.5% of 
volunteers will develop 
symptoms that 
require rtPCR. Services will 
be provided by recruitment 
sites  
71  
 $                250,000.00    $           17,750,000.00   
6  
Laboratory tests (Creatinine, 
CBC, ALT, AST, BHCG for 
women (80% of volunteers) 
and rtPCR for all subjects.   
Pontificia  
Universidad  
Javeriana  
Laboratory tests for each 
participant (80% women; 
20% men)   
1  
 $         285,512,810.00    $         285,512,810.00   
7  IgG antibody tests for follow up 
4  
Pontificia  
Universidad  
Javeriana  
IgG antibody tests for 
follow up 4   
1  
 $           43,320,000.00    $           43,320,000.00   
8  
Recruitment services  
Pontificia  
Universidad  
Javeriana  
Recruitment costs per 
volunteer including PPE + 
workhours of 
pharmaceutical 
chemist, respiratory 
therapist, 
assistant nurse, and 
laboratory assistant  
950  
 $                     105,699    $              100,414,240   
   
TOTAL  
   
   
   
   
$1,146,879,944   
  
  
  
9.2 Materials and supplies  
No.  
  Item  
Site  
Justification  
Quantity  
Unit value  
(cop)  
Subtotal  
(cop)  

1  
IgG antibody 
tests box (20 kits)  
Pontificia  
Universidad  
Javeriana  
Antibody test for 342 
subjects at baseline; 
950 for follow-up 1, 475 
for follow-up 3   
(Brand: Biosensor) 
55  
$ 780,000  
$ 42,666,000  
2  
Placebo; 60 units 
X 475 volunteers  
Pontificia  
Universidad  
Javeriana  
475 volunteers X 
60 days  
30000  
$ 200   
$ 6,000,000   
3  
Investigational 
drug TDF/FTC  
Pontificia  
Universidad  
Javeriana  
475 volunteers X 
60 days  
30000  
$ 800   
$ 24,000,000   
  
  
  
  
  
  
$ 72,666,000  
  
  
  
9.3 Total budget  
  
Item  
Funded by grant   Pontificia Universidad Javeriana  
offsetting  
Hospital Universitario San 
Ignacio offsetting  
Total  
Cash  
In kind  
Cash  
In kind  
Registry and certification 
costs  
$0.00 
$0 
$0  
$0  
$0 
$0 
Equipment  
$0.00 
$0 
$0  
$0  
$0 
$0 
Materials and supplies  
$67,876,084 
$4,789,916 
$0  
$0  
$0 
 $     72,666,000  
Scientific staff  
$0.00 
$0 
$18,322,123  
$0  
$172,708,003 
 $   191,030,126  
Support staff  
$284,472,000 
$0 
$0  
$0  
$0 
 $   284,472,000  
Publications  
$28,000,000 
$0 
$0  
$0  
$0 
 $     28,000,000  
Technical support and 
assistance services  
$23,690,536 
$0 
$0  
$0  
$0 
 $     23,690,536  
Technical services  
$1,131,535,948.00 
$15,343,996 
$0  
$0  
$0 
 $1,146,879,944  
Management (7%)  
$107,490,220 
$0 
$0  
$0  
$0 
 $   107,490,220  
CTEI instrument management 
(5%)  
$82,153,239 
$0 
$0  
$0  
$0 
 $     82,153,239  
TOTAL  
$1,725,218,040 
$20,133,912 
$18,322,123  
$0  
$172,708,003 
$1,936,382,066 
 
Appendix 1.   
Clinical 
trials on prophylaxis 
for 
COVID-19 
with TF/FTC currently 
registered in 
ClinicalTrials.gov  
  
Study  
Recruitment  Study site  
Description and 
objectives  
Outcomes  
Design  
Clinical Trial for the 
Prevention of SARS-
CoV-2 Infection 
(COVID-19) in 
Healthcare Personnel 
(EPICOS)  
Recruiting  
Plan Nacional 
sobre el Sida 
(PNS), Spain  
To evaluate the efficacy of 
a daily single dose of 
TDF/FTC (245/200 mg) or 
a daily single dose of 
hydroxychloroquine or 
combination of both vs 
placebo for prevention of 
COVID-19. 4000 
volunteers will be included 
assigned to treatment arm 
in proportion of 1:1:1:1. 
The length of treatment 
will be 12 weeks. Follow-
up will go on for 4 weeks 
after completion of 
treatment. Interim 
analyses will be 
performed monthly.  
 
Number of 
symptomatic serology confirmed 
SARS-CoV-2 infections.  
Number of asymptomatic 
serology confirmed SARS-CoV-
2 infections.  
 
Severity of COVID-19, 
determined as follows:  
- Duration of symptoms.  
- Relationship between 
treatment duration 
and development of symptoms.  
- Relationship between 
treatment duration and duration 
of symptoms.  
- Seroconversion of IgM/IgG 
since development of 
symptoms.  
Study type: Clinical trial.  
Number of participants: 
4000.  
Allocation: randomized.  
Trial design: parallel.  
Masking: double.  
Primary outcome: 
protection.  
Estimated recruitment start 
date: April 1, 2020.  
Estimated recruitment end 
date: June 30, 2020.  
Estimated   completion 
date: July 31, 2020.  

TAF/FTC for Pre-
exposure Prophylaxis 
of COVID-19 in 
Healthcare Workers 
(CoviPrep Study)- 
ARGENTINA  
Not yet 
recruiting  
Hospital 
Italiano, 
Buenos Aires, 
Argentina  
To evaluate the efficacy of 
TAF/FTC for 12 weeks vs 
placebo for the prevention 
of COVID-19 in health 
care workers.  
Number of symptomatic or 
asymptomatic COVID-
19 cases assessed by 
antibodies and confirmed 
by rtPCR.   
Number 
of asymptomatic serology 
confirmed COVID-19.  
Severity of symptoms defined 
as follows:   
- Mild: malaise, fever, cough, 
myalgia, arthralgia.  
- Moderate: shortness of 
breath.   
- Severe: requirement of 
intensive care.   
Duration of symptoms.   
Relationship between treatment 
and duration of symptoms.   
Time to seroconversion.   
Study type: Clinical trial.   
Number of participants: 
1378  
Allocation: randomized.  
Trial design: parallel  
Masking: triple.   
Primary outcome: 
protection.   
Estimated recruitment start 
date: June 15, 2020.   
Estimated recruitment end 
date: non specified.   
Estimated completion date: 
November 11, 2020  
 
A real-world study for 
lopinavir/ritonavir 
(LPV/r) 
and emtritabine (FTC) 
/ Tenofovir 
alafenamide 
Fumarate tablets 
(TAF) regimen in the 
treatment of novel 
coronavirus 
pneumonia (COVID-
19)- CHINA  
Not yet 
recruiting  
Sichuan 
Academy of 
Medical 
Sciences & 
Sichuan 
Provincial 
People's 
Hospital  
Real-life stydy. Non-
randomized non-blinded 
study of treatment of 
health care professionals 
with TAF/FTC plus LPV/r 
vs LPV/r alone. Duration 
not specified.   
 
Primary outcome: survival rate.   
Secondary outcomes:   
-Time to negative rtPCR.  
-Time to ARDS development.   
- Hospitalization length.   
  
Study type: real 
life interventional study.   
Number of participants: 
120.   
Allocation: non-specified.   
Masking: no masking.   
Primary outcome: 
protection.   
Estimated recruitment start 
date: February 2, 2020.   
Estimated recruitment end 
date: not specified.   
Estimated completion date: 
June 30, 2020.   
  
  
  
  
  
  
Appendix 2. Drug interactions of TDF/FTC  
Drugs not allowed in the trial.  
 
 
Analgesics  
Chronic use (two or more weeks) of any of the following:  
Celecoxib,  
 Diclofenac,  
Ibuprofen  
Methadone  
Naproxen  
Nimesulide  
Piroxicam  
 
 
Antiarrhythmics  
Amiodarone  
Quinidine  
Antibiotics  
 
 
 
 

Amikacin  
Cefalexin  
Clarithromycin  
Gentamicin  
Piperacillin/ Tazobactam  
Rifampicin  
Sulfadiazine  
Vancomycin  
Contraceptives  
Ethinyl estradiol and norgestimate  
Anticonvulsants  
Topiramate  
Antidepressants  
Lithium  
Antidiabetics  
Canagliflozin  
Empagliflozin  
Antifungal  
Amphotericin B  
Fluconazole  
Itraconazole  
Flucytosine  
Ketoconazole  
Antiretrovirals  
Dolutegravir/Lamivudine  
Abacavir  
Didanosine  
Lamivudine  
Atazanavir/cobicistat  
Atazanavir/ritonavir  
Darunavir/ritonavir  
Darunavir/cobicistat  
Indinavir  
Antivirals  
Acyclovir  
Ganciclovir  
Ledipasvir/Sofosbuvir  
Sofosbuvir/Velpatasvir  
Calcium channel blockers  
Verapamil  
Antihypertensives / Heart failure  
Furosemide  
Hydralazine  
Sacubitril  
Immunomodulators  
Interferon  
Hydroxyurea  
Immunosuppressors  

Ciclosporin  
Mycophenolate  
Sirolimus  
Tacrolimus  
Others  
Acetazolamide  
Orlistat  
Probenecid  
Pyridostigmine  
Sevelamer  
Zoledronic Acid  
 
  
Low interaction drugs allowed in the trial:  
  
  
References  
  
 
HIV Drug interactions. University of Liverpool.   
https://www.hiv-druginteractions.org/view_all_interactions/445855  
  
 
Ficha técnica TDF/FTC TRUVADA Gilead Sciences Ireland UC  
https://www.ema.europa.eu/en/documents/product-information/truvada-epar-
product-information_es.pdf  
 
Appendix 3. Variables  
Inclusion-exclusion criteria   
Variable  
Variable type   
Conceptual definition  
Operative definition  
Informed consent signature 
date  
Quantitative  
Informed consent signature date  
Day/Month/Year  
Age  
Qualitative/dichoto
mous  
Age 18 to 70 years according to legal ID  
0- No  
1- Yes  
Profession  
Qualitative/nominal
 
Profession  
1- Physician  
2- Nurse  
3- Nursing assistant  
4- Respiratory therapist  
Caring for COVID-19 patients  Qualitative/dichoto
mous  
Subject has direct contact with confirmed or
suspected COVID-19 patients  
0- No  
1- Yes  
Serology IgG for SARS-CoV-2  Qualitative/dichoto
mous  
Result of serology IgG test for COVID-19 before
randomization and administration of drug/placebo  
0- Negative  
1- Positive  
 
Baseline RT-PCR for SARS-
CoV-2  
Qualitative/dichoto
mous  
Result of RT-PCR for SARS-CoV-2 of nasopharyngeal
swab before randomization and administration
of drug/placebo   
0- Negative  
1- Positive  
 
Exclusion criteria  
COVID-19 related symptoms  Qualitative/dichoto
mous  
Presence of two or more of the following at initial 
screening:  
- Body temperature ≥ 38 °C  
- Acute cough (onset less than 10 days)  
- Shortness of breath  
- Sore throat  
- Malaise.   
- Acute diarrhea  
0- No  
1- Yes  

History of COVID-19  
Qualitative/dichoto
mous  
History of serology or rtPCR confirmed COVID-19  0- No  
1- Yes  
Cohabitation with people 
with COVID-19 infection or 
COVID-19 symptoms  
Qualitative/dichoto
mous  
Cohabitation with people with COVID-19 infection
or COVID-19 symptoms  
0- No  
1- Yes  
Treatment during last month 
with medications that have 
significant interactions with 
TDF/FTC  
Qualitative/dichoto
mous  
Treatment during last month with medications that 
have significant interactions with TDF/FTC (see
Appendix 2)  
0- No  
1- Yes  
HIV infection   
Qualitative/dichoto
mous  
Confirmed HIV infection  
 
0- No  
1- Yes  
B hepatitis immunity  
Qualitative/dichoto
mous  
Volunteer with anti-HBsAg less than 10 UI/ml  
0- No  
1- Yes  
Hepatitis B infection  
Qualitative/dichoto
mous  
History of hepatitis B virus infection  
0- No  
1- Yes  
Recent use of TDF/FTC  
Qualitative/dichoto
mous  
Use of TDF/FTC within the last month for any other
indication  
0- No  
1- Yes  
Hypophosphatemia  
Qualitative/dichoto
mous  
Phosphorus serum concentration less than lower
reference laboratory value  
0- No  
1- Yes  
Liver disfunction  
Qualitative/dichoto
mous  
Liver disfunction as defined by ALT or AST levels ≥
2 times upper limit of normal (x ULN) (66)  
0- No  
1- Yes  
Hematologic disfunction  
Qualitative/dichoto
mous  
Hemoglobin concentration less than 11 mg/dl or
neutrophil count less than 1000 cel/mm3  
0- No  
1- Yes  
Chronic kidney disease  
Qualitative/dichoto
mous  
eTFG ≤ 60 mL/min/1.73 m2, calculated by CKD-EPI
formula with baseline creatinine or past history of
chronic kidney disease as disclosed by volunteer  
0- No  
1- Yes  
Hypersensitivity to TDF/FTC  Qualitative/dichoto
mous  
History of hypersensitivity to TDF/FTC  
0- No  
1- Yes  
Metabolic bone disease  
Qualitative/dichoto
mous  
History of osteopenia, osteoporosis or pathologic
fractures  
0- No  
1- Yes  
Pregnancy, breastfeeding 
or plans to seek pregnancy 
during the study  
Qualitative/dichoto
mous  
Pregnancy, 
breastfeeding 
or plans 
to 
seek
pregnancy 
during 
the foreseen 
duration 
of
participation in the study  
0- No  
1- Yes   
2- Not applicable  
Pregnancy test  
Qualitative/dichoto
mous  
Result of quantitative serum Beta-HCG above the
limit of detection of laboratory for non-pregnant
women  
0- No  
1- Yes   
2- Not applicable  
Participation in another 
study  
Qualitative/dichoto
mous  
Participation in any other study of prevention of 
COVID-19  
0- No  
1- Yes  
Withdrawal criteria   
Kidney disfunction  
Qualitative/dichoto
mous  
Any 
grade 
2 kidney 
function
adverse evento during the study  
0- No  
1- Yes  
Related Serious adverse 
evento   
Qualitative/dichoto
mous  
Any serous adverse event deemed to be related to
study intervention as assessed by investigators  
0- No  
1- Yes  
Voluntary withdrawal  
Qualitative/dichoto
mous  
The volunteer decides to withdraw from study for 
any reason  
0- No  
1- Yes  
Requirement of any 
medication with significant 
interactions  
Qualitative/dichoto
mous  
Requirement of any medication that has significant
interactions with TDF/FTC during participation in
study  
0- No  
1- Yes  
Demographic variables  
Age  
Quantitative/contin
uous  
Age of volunteer at the beginning of the study  
Number of years  
Randomization date  
Quantitative/contin
uous  
Randomization date  
Day/Month/Year  
Date drug/placebo start  
Quantitative/contin
uous  
Date of drug/placebo start  
Day/Month/Year  
Sex  
Cualitativa/ 
nominal   
Birth sex of patient   
1- Feminine  
2- Masculine  
Site  
Cualitativa/ 
nominal  
Research site where volunteer works   
1-Hospital Universitario San 
Ignacio  
2-Clínica Colombia  
3-Clínica Reina Sofia  

4-Clinica Santa María del Lago  
5-Hospital Universitario 
Nacional  
6-Clínica Samaritana-Bogotá  
7-Clínica Samaritana-
Zipaquira  
8-Hospital San Jorge  
Profession  
Qualitative/nominal
 
Profession  
1- Physician  
2- Nurse  
3- Nursing assistant  
4- Respiratory therapist  
Department  
Qualitative/nominal
 
Hospital department in which volunteer works.
Multiple answers possible  
1- Emergency department  
2- Hospitalization floors  
3- ICU  
Time of daily exposure to 
COVID-19 patients  
Quantitative/contin
uous  
Declared average time of daily exposure per
volunteer to COVID-19 patients  
Number of hours  
Shift  
Qualitative/nonomi
no  
Volunteer’s work shifts  
1- Morning  
2- Afternoon  
3- Night  
4- Whole day  
5- Whole day and night shifts  
Number of institutions in 
which volunteer works  
Quantitative/    disc
rete  
Number of institutions in which volunteer works  
Number of institutions  
Physician role in institution  Qualitative/nonomi
no  
Role of physician in the institution  
1. 
Intern  
2. 
General 
practitioner  
3. 
Resident  
4. 
Specialist  
5. 
Not applicable  
Specialty  
Qualitative/nonomi
no  
Physician’s specialty (or residency)  
1. 
Emergency 
medicine  
2. 
Internal medicine  
3. 
Adult intensive 
care  
4. 
Pediatric intensive 
care  
5. 
Geriatrics  
6. 
Anesthesiology  
7. 
Pediatrics  
8. 
Neonatology  
9. 
Surgery  
10. 
Surgical 
specialties   
11. 
Pulmonology  
12. 
Infectious diseases  
13. 
Other  
14. 
Not applicable  
Weight  
Quantitative/contin
uous  
Weight at enrollment measured with a calibrated
clinical scale   
Weight in kilograms with 
one decimal  
Height  
Quantitative/contin
uous  
Height at enrollment measured with a clinical
stadiometer  
Height in centimeters without 
decimals  
Number of cohabitating 
people  
Quantitative/discret
e  
Number of people that cohabit with volunteer  
Number of people  
Comorbidities  
Chronic obstructive 
pulmonary disease (COPD)  
Qualitative/dichoto
mous  
History of confirmed COPD as disclosed by the
patient  
 
0- No  
1- Yes  
Cardiovascular disease   
Cualitative/nominal  History of hypertension, stroke, peripheral artery
disease, heart failure  
1- No  
2- HTA  
3- Stroke  
4- PAD  
5- HF  
Diabetes mellitus  
Qualitative/nominal
  
Classification of diabetes mellitus  
0- No  
1-Diabetes tipo I  
2-Diabetes tipo II  

Diabetes control  
Qualitative/nonomi
no  
Controlled diabetes: 
defined 
as 
glycated A1C
hemoglobin (HbA1C) equal or less than 7% within
the last 3 months.   
Uncontrolled diabetes: defined as HbA1C higher
than 7%.  
1-Uncontrolled diabetes  
2-Controlled diabetes  
3-No HbA1C data  
  
Data to be collected in Follow-up 1, Follow-up 2 y Follow-up 3  
Follow-up date  
Quantitative/contin
uous  
Date  
Day/Month/Year   
COVID-19 related symptoms  Qualitative/dichoto
mous  
Development of 
any 
of the 
following
symptoms:                                                                         
                           
- Fever: body temperature higher than 38°C  
- Acute cough (start within the last 10 days)  
- Shortness of breath  
- Rhinorrhea  
- Sore throat  
- Malaise  
- Acute diarrhea  
- Anosmia or hyposmia  
- Dysgeusia  
- Headache  
 
0- No symptoms  
1- Fever  
2- Acute cough  
3- Shortness of breath  
4- Rhinorrhea  
5- Sore throat  
6- Malaise  
7- Acute diarrhea  
8- Anosmia or hyposmia  
9- Dysgeusia  
10- Headache  
11- Other, Specify  
  
Date of symptom start  
Quantitative/contin
uous  
Date of start of first COVID-19 related symptom. If
no symptoms register 00/00/00.  
Day/Month/Year  
Adverse event (AE)  
Quantitative/nomin
al  
Any untoward adverse event during administration
of investigational product that may or may not have
a causal relationship with it.  
0-No  
1-Yes  
Serious adverse event (SAE)  Qualitative/nonomi
no  
Any adverse event that:   
- Results in death.  
- Threatens life and requires hospitalization or 
prolongation of hospitalization.  
- Results in permanent or prolonged inability or 
disability.  
- Causes congenital defects or malformations.  
0-No  
1-Yes  
Serious adverse 
event classification  
Qualitative/nonomi
no  
Expected SAE:   
An AE whose nature and severity is consistent
with what is described in investigator’s brochure or
drug insert.   
 
Unexpected SAE:  
An 
AE 
whose natura and 
severity 
are 
not
consistent with what is described in investigator’s
brochure or drug insert.  
1- Expected serious adverse 
event  
2- Unexpected serious adverse 
event  
Fatal SAE   
Qualitative/nonomi
no  
SAE that results in death  
0- No  
1- Yes  
Type of SAE  
Qualitative/nonomi
no  
Type of SAE the volunteer developed  
1- Acute kidney injury  
2- Proximal tubulopathy  
3- Emesis  
4- Abdominal pain   
5- Headache  
6- Insomnia  
7- Diarrhea  
8- Hypersensitivity skin 
reaction  
9- Steven-Johnson’s 
syndrome  
10- Maculopapular rash  
11- Appendicitis  
12- Pancreatitis  
13- Other, specify  
Date of SAE start   
Quantitative/contin
uous  
Date when SAE started  
Day/Month/Year  
Date of SAE end   
Quantitative/contin
uous  
Date when SAE ended  
Day/Month/Year  

Non serious AE  
Qualitative/nonomi
no  
Whether volunteer developed non serious AE  
0- No  
1- Yes  
Type of non-serious AR  
Qualitative/nominal
 
Type of non serious AE that volunteer developed  1- Nausea  
2- Headache  
3- Abdominal pain  
4- Flatulence  
5- Weakness or tiredness  
6- Insomnia  
7- Fatigue  
8- Vomiting  
9- Maculopapular rash   
10- Steven-Johnson’s 
syndrome  
11- Allergic skin reaction  
12- Other, specify  
Nausea   
Qualitative/nonomi
no  
A feeling of sickness featured by an urge to vomit.  1-Grade 1  
2-Grade 2  
3-Grade 3  
Headache  
Qualitative/nominal
 
Headache   
1-Grade 1  
2-Grade 2  
3-Grade 3  
Abdominal pain  
Cualitativa/ 
Nominal  
A feeling of distress or pain in abdominal area.   
1-Grade 1  
2-Grade 2  
3-Grade 3  
Flatulence  
Qualitative/nonomi
no  
A disorder highlighted by abnormally increased gas
discharge by lower gastrointestinal tract.   
1-Grade 1  
2-Grade 2  
Insomnia  
Qualitative/nominal
 
A disorder characterized by difficulty to start or
maintain sleep.   
1-Grade 1  
2-Grade 2  
3-Grade 3  
Vomit   
Qualitative/nonomi
no  
A disorder featured by a reflex act or actively 
regurgitating stomach contents through mouth  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
5-Grade 5  
Maculopapular skin rash  
Qualitative/nominal
 
A disorder featured by the appearance of macules
and 
papules. Also 
known 
as
morbilliform eruption. Often associated with prurit
us.  
1-Grade 1  
2-Grade 2  
3-Grade 3  
 
Steven-Johnson’s syndrome  Qualitative/nominal
 
A disease in which at least 10% of body surface 
area develops a severe sphacelating lesions and 
bullae, also compromising mucosal membranes.   
3-Grade 3  
4-Grade 4  
5-Grade 5  
Allergic reaction  
 
Qualitative/nominal
 
A disorder featured by a local or diffuse skin 
reaction upon exposure to an allergenic.   
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
5-Grade 5  
Other allergic reaction  
Qualitative/nominal
 
Se coloca la clasificación de la reacción alérgica 
reportada según la   
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
5-Grade 5  
Adherence by tablet count   Qualitative/discrete
 
Number of drug/placebo tablets taken to follow-up 
date  
Number of tablets  
Drug/placebo interruption  
Qualitative/dichoto
mous  
Any interruption of investigational product  
0- No  
1- Yes  
Days of product interruption  Quantitative/discret
e  
Days of drug interruption  
Number of days  
Cause of drug interruption  
Qualitative/nominal
 
Reason of drug interruption  
1- Omission  
2- AE  
3- Accidental los of 
drug/placebo  
4- Non-availability of 
drug/placebo  
Additional data to be collected in Follow-up 2 and 3  

Temperature  
Quantitative/contin
uous  
Body temperature in Celsius degrees  
Temperature in Celsius 
degrees  
Heart rate  
Quantitative/discret
e  
Heart rate  
Heart rate in beats per 
minute  
Respiratory rate  
Quantitative/discret
e  
Respiratory rate  
Respiratory rate in 
respirations per minute  
Systolic blood pressure  
Quantitative/discret
e  
Systolic blood presure  
Systolic blood pressure in 
mmHg  
Diastolic blood pressure  
Quantitative/discret
e  
Diastolic blood presure  
Diastolic blood pressure in 
mmHg  
Creatinine  
Quantitative/contin
uous  
Serum creatinine concentration (mg/dl).   
Serum creatinine 
concentration (mg/dl).  
Creatinine rise  
Qualitative/nominal
 
Severity of creatinine rise  
0-Normal0  
1-Grado 1  
2-Grado 2  
3-Grado 3  
4-Grado 4  
IgG forSARS-CoV-2  
Qualitative/dichoto
mous  
Result of serology test for SARS-CoV-2 (only for 
follow-up 2)  
0- Negative  
1- Positive  
Data to be collected in follow-up 3  
Platelets  
Quantitative/discret
e  
Number of platelets in complete blood count (CBC)  Number of platelets 
per microliter (Cels/μl).  
Thrombocytopenia   
Qualitative/nominal
 
Severity of thromocytopenia  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
Hemoglobin (Hb)  
Qualitative/continu
ous  
Hemoglobin concentration in CBC  
Hb (g/dl).   
Anemia   
Qualitative/nominal
 
Classification of severity of anemia  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
Lymphocytes  
Quantitative/discret
e  
Number of lymphocytes in complete blood count
(CBC)  
Number 
of lymphocytes per microliter (
Cels/μl).  
Lymphopenia   
Qualitative/nominal
 
Classification of severity of lymphopenia  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
Neutrophils  
Quantitative/discret
e  
Number of neutrophils in complete blood count
(CBC)  
Number 
of neutrophils per microliter (
Cels/μl).  
Neutropenia  
Qualitative/nominal
 
Classification of severity of neutropenia  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
Aspartate 
aminotransferase (AST)  
Quantitative/contin
uous  
AST 
concentration 
in international 
units 
per
litter (UI/l)   
AST (UI/l).   
Aspartate aminotransferase 
elevation   
Qualitative/nominal
 
Severity of elevation of AST  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  
Alanine 
aminotransferase (ALT)  
Quantitative/contin
uous  
ALT concentration in international units per litter
(UI/l)  
ALT (UI/l).   
Alanine aminotransferase ele
vation   
Qualitative/nominal
 
Severity of elevation of ALT  
0-Normal  
1-Grade 1  
2-Grade 2  
3-Grade 3  
4-Grade 4  

Pregnancy test   
Qualitative/dichoto
mous   
Applicable 
only 
to 
women. 
Result
of quantitative serum 
Beta-HCG 
test regarding
upper reference value for non-pregnant women.   
0- Negative  
1- Positive  
RT-PCR SARS-CoV-2  
Qualitative/dichoto
mous  
Detection of SARS-CoV-2 by RT-PCR de   
0- Undetectable  
1- Detectable   
Data to be collected only in Follow-up 4  
Follow-up date  
Quantitative/contin
uous  
Follow-up date   
Day/month/year  
COVID-19 related symptoms  Qualitative/dichoto
mous  
Development 
of 
any 
of the 
following
symptoms:                                                                         
                           
- Fever: body temperature higher than 38°C  
- Acute cough (start within the last 10 days)  
- Shortness of breath  
- Rhinorrhea  
- Sore throat  
- Malaise  
- Acute diarrhea  
- Anosmia or hyposmia  
- Dysgeusia  
- Headache  
 
0- No symptoms  
1- Fever  
2- Acute cough  
3- Shortness of breath  
4- Rhinorrhea  
5- Sore throat  
6- Malaise  
7- Acute diarrhea  
8- Anosmia or hyposmia  
9- Dysgeusia  
10- Headache  
11- Other, Specify  
 
Date of symptom start  
Quantitative/contin
uous  
Date of start of first COVID-19 related symptom. If
no symptoms register 00/00/00.  
Day/Month/Year  
Temperature  
Quantitative/contin
uous  
Body temperature in Celsius degrees  
Temperature in Celsius 
degrees  
Heart rate  
Quantitative/discret
e  
Heart rate  
Heart rate in beats per 
minute  
Respiratory rate  
Quantitative/discret
e  
Respiratory rate  
Respiratory rate in 
respirations per minute  
Systolic blood pressure  
Quantitative/discret
e  
Systolic blood presure  
Systolic blood pressure in 
mmHg  
Diastolic blood pressure  
Quantitative/discret
e  
Diastolic blood presure  
Diastolic blood pressure in 
mmHg  
Serology IgG for SARS-CoV-2  Qualitative/dichoto
mous  
Result of serology IgG test for COVID-19 before
randomization and administration of drug/placebo  
0- Negative  
1- Positive  
 
Dependent variables/primary outcomes  
Development of COVID-19  
Qualitative/dichoto
mous  
Positive RT-PCR for SARS-Cov-2 at any time during
follow-up   
0- No  
1- Si  
Date of positive RT-PCR for 
SARS-CoV-2  
Quantitative/contin
uous  
Date of positive result   
Day/Month/Year  
Time to positive 
result positive RT-PCR for 
SARS-CoV-2  
Quantitative/discret
e  
Time 
between start of administration 
of
drug/placebo to a positive RT-PCR result.  
Number in days  
Symptoms probably related 
to COVID-19  
Qualitative/nominal
 
Recording 
of 
presence 
or 
absence of
solicited symptoms probably related to COVID-19
during each of 4 follow-up visits.   
0-None  
1-Fever  
2-Acute cough  
3-Shortness of breath  
4-Rinorrhea  
5-Sore throat  
6-Malaise  
7-Acute diarrhea  
8-Anosmia hyposmia  
9-Dysgeusia   
10-Mialgya  
11-Other, specify  
 
Date of symptom start  
Quantitative/contin
uous  
Date of start of first COVID-19 related symptom. If
no symptoms register 00/00/00.  
Day/Month/Year  
Time to development of first 
COVID-19 related symptom  
Quantitative/discret
e  
Number of days between start of administration of
drug/placebo and appearance of first COVID-19
related symptom  
Number of days  
Dependent variables/secondary outcomes  

Withdrawal of investigational
product  
Qualitative/nominal
 
Decision 
by 
investigator 
or patient
to withdraw investigational 
product
before planned.   
0-Not aplicable  
1- Withdrawal due to kidney 
disfunction.    
2- Withdrawal due to need 
for new interacting medicatio
ns.   
3- Withdrawal due to 
development of any SAE 
deemed to be related to 
intervention.   
4- Withdrawal due to any AE 
that makes the volunteer 
decide to interrupt 
investigational product.   
5-Voluntary withdrawal.  
Date of investigational 
product withdrawal  
Quantitative/contin
uous  
Date of discontinuation of investigational product,
only if previous answer was other than 0  
Day/month/year  
Time to discontinuation of 
investigational product   
Quantitative/discret
e  
Time between initiation of investigation product to
discontinuation  
Number of days   
Severity of COVID-19  
Qualitative/nominal
 
Classification of severity as follows:  
- Asymptomatic infection  
- Mild disease: defined as not requiring 
hospitalization.   
- Moderate disease: defined as requiring 
hospitalization outside of the ICU.   
- Severe disease: defined as 
requiring hospitalization in ICU.   
1-Asymptomatic  
2-Mild  
3-Moderate  
4-Severe  
Date of hospitalization start  Quantitative/contin
uous  
Date of hospitalization start   
Day/month/year  
Date of hospital discharge  
Quantitative/contin
uous  
Date of hospital discharge  
Day/month/year  
Date of ICU admission  
Quantitative/contin
uous  
Date of ICU admission   
Day/month/year  
Fecha de egreso del UCI  
Quantitative/contin
uous  
Date of ICU discharge or date of death  
Day/month/year  
Date of recovery from COVID-
19  
Quantitative/contin
uous  
Recovery from COVID-19 defined as a minimum
of 10 days after symptom start plus at least 72 hours
of 
symptom 
improvement. 
If 
the patient
died, record 00/00/00  
Day/month/year  
Final status  
Quantitative/contin
uous  
Record of volunteer status at the end of follow-up  0- Death  
1- Alive  
Date of end of follow-up  
Quantitative/contin
uous  
Date of end of follow-up  
Day/month/year  
 
 
Appendix 4. Informed consent format  
  
  
MANAGEMENT OF CLINICAL 
RESEARCH  
  

     
  
 
  
  
INFORMED CONSENT IN 
CLINICAL RESEARCH 
PROJECTS  
  
  
  
 
 
 
 
 
 
 
       
  
                                           
      
    
 
  
INTRODUCTION  
 
Volunteer’s code: ________________  
 
This informed consent format is intended for use in a project with subjects that can consent 
participation. In this document “you” refers to the research volunteer or participant.   
  
You are being invited to participate in the research project “effectiveness of personal 
protective elements plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 
prevention of transmission of SARS-CoV-2 in previously healthy adult health care workers 
younger than 60 years.” This document will give you the necessary information to participate 
willingly and freely. This project is conducted by Pontificia Universidad Javeriana, Hospital 
Universitario San Ignacio, Clínica Colsanitas (Clínica Universitaria Colombia see, Clínica Reina 
Sofía see, Clínica Santa María del Lago see), Fundación Universitaria Sanitas, Hospital 
Universitario Nacional de Colombia, Hospital Universitario de la Samaritana E.S.E, Hospital 
Universitario de la Samaritana Unidad Funcional Zipaquirá, Universidad del 
Quindío, Fundación Universitaria Autónoma de Las Américas, Hospital Universitario San 
Jorge and La Universidad Tecnológica de Pereira. Before consenting, you need to 
fully understand the purpose of your decision. This process is called informed consent. 
Once you have read this document and solved with the investigator any doubt, you will be 
asked whether you want to participate in this study.    
GENERAL INFORMATION  

 
Why is this study carried out?   
 
The pandemic of COVID-19 caused by SARS-CoV-2 is an event of interest in public health that 
directly affects health care workers. Social distancing and temporary isolation of infected 
people and their contacts are the main strategies to contain the spread of disease. However,
health care workers are at increased risk of infection.  
 
Personal protective equipment (PPE) is required for assisting suspected or confirmed COVID-
19 and other preventive strategies have been proposed. That is why this research will evaluate 
the use of TDF/FTC as prevention of SARS-CoV-2 transmission in health professionals.   
 
TDF/FTC is a drug routinely used for treatment of HIV and Hepatitis B infection. It has an 
established safety profile and has been evaluated for prophylaxis of HIV infection in at risk 
populations. Additionally, its inhibitory activity on ARN dependent ARN polymerase of SARS-
CoV-2 has been confirmed in biologic models.  
 
 
What is the aim of this study?   
 
To evaluate the efficacy and safety of TDF/FTC (300/200 mg/day) in addition to the use of 
personal 
protective 
equipment 
for 
the 
prevention 
of SARS-CoV-2 infection 
in 
health professionals that care for COVID-19 patients in the emergency department, hospital 
ward and intensive care unit.   
 
 
How will the study be carried out?   
 
It is a randomized clinical trial with triple masking (which means neither you nor the 
investigators that directly take care of you or the personnel performing statistical analyses, will
know whether you are receiving  TDF/FTC or placebo) that involves health professionals 
(physicians, nurses, nurse assistants, respiratory therapists) in the emergency department, 
hospitalization ward and ICU.   
 
During initial screening, we will perform a clinical assessment, laboratory blood tests, and 
molecular (nasal swab) and antibody tests to rule out the presence of SARS-CoV-2 before 
starting your participation. Women will also receive a pregnancy tests and will be excluded in 
case of a positive result.  
 
Eligible participants will be randomly assigned to one of two groups: TDF/FTC 
(300/200 mg) once daily for 60 days plus PPE or placebo plus PPE. The participant will attend a
baseline visit and 4 follow-up visits at days 20, 40 and 60 after starting the investigational 
product, and 15 days after  ending-up investigational product administration (75 days after 
baseline visit). During these visits, we will perform clinical assessment, look for adverse events, 
confirm adherence to treatment, and take samples for the aforementioned tests, including tests 
for detection of COVID-19.   
 

We may also perform an additional virtual or telephonic follow up in between visits, and require 
you to keep a diary of adherence, symptoms and adverse events and use of PPE.   
 
In case of developing COVID-19, treatment will be withheld and we will give you 
recommendations to consult with your EPS or ARL, while keeping a telephonic follow up. This 
will be reported to the institutional review board (IRB) and also to SIVIGILA, as required by the 
authorities.   
 
 
What are the risks involved in your participation?  
 
There are risks involved with the participation of this study. The most frequently reported risk in
clinical trials (25-32%) independently of receiving the investigational intervention or placebo 
are:   
 
o Nausea  
o Headache  
o Abdominal pain, bloating  
Less frequently  
o Malaise, fatigue  
o Sleep disturbances  
o Diarrhea  
o Skin rash  
o Kidney disfunction associated to the use of TDF/FTC, which comprises a variaty of
manifestations, including proximal tubular disfunction, acute kidney injury, diabetes 
insipidus. However, it is infrequent, and it presents in less than 1% of patients that use it for 
less than six months. For that reason, people with baseline kidney disfunction defined as 
estimated glomerular filtration rate less than 60 ml/min/1,72 m2 will be excluded, as will 
people taking other potentially nephrotoxic medications.   
o Acute severe exacerbation of B hepatitis. To avoid this possibility, all people without 
immunity to B hepatitis, defined as Anti-HBs less than 10 UI/ml will be excluded.   
o Loss of bone mineral density. This effect has been described after six months of use and 
are reversible after drug withdrawal.   
Most of adverse events are mild. Serious adverse events are much more infrequent 
and depend of a prolonged use of the medicines.  In previous studies involving TDF/FTC for 
prophylaxis, less than 2% of participants suspended the medication due to adverse events.   
 
The length of treatment in this study will be short, thus minimizing the risk of serious adverse 
events.   
 
Additionally, you may present discomfort associated with sample drawing. A total of 4 samples 
are scheduled (one prior to starting the drug and again on days 40, 60 and 75 after initiation of 
treatment), during which you may feel:   
 
o Pain and bruises in puncture sites.   

o You may also feel discomfort (cough, irritation and pain of nasal or nasopharyngeal 
mucosa, nausea, vomiting) associated with nasopharyngeal swab, of which you will receive 
at least two, one prior to starting the medication and one at day 60.   
 
 
What are the potential benefits of my participation in the study?    
 
o In case of intervention being effective, you may have your risk of developing COVID-19
reduced.   
o You may also contribute to acquire information that will help other health care 
workers.   
o You may also benefit to access to early diagnosis of infection.   
  
 
Will there be confidentiality with management of my data?   
 
This Project is subjected to law 1581 of 2012 (Habeas data) that applies for the treatment of 
personal data. When signing this document you agree to the use of your personal data by the 
investigators.   
 
Only the members of the research team will know that you are participating in the study. Your 
records will be stored granting confidentiality by using a ciphered database in the 
software REDCap, which is held by Hospital Universitario San Ignacio. The database has 
controlled access using individual passcodes and it is restricted to the data analysis personnel.  
 
All the study forms will be assigned a unique code that differs from your legal identification 
number. None of your personal data, such as name, address, telephone number or ID, will be 
used in any of the study forms, except for this informed consent form.   
 
You will have the possibility of knowing and requiring rectification of all your personal data, and
to withdraw your consent for personal data use.   
 
 
Is there any financial obligation for me?   
 
You will incur in no financial obligation or expenditure while participating in this trial.   
 
 
How long will be my participation in the study?  
 
Your expected participation time will be approximately 65 days (between 65 and 80 days), 
taking into account that if you develop COVID-19 at the end of the study, we will perform a 
telephone follow up to define the duration of infection and we may take some additional tests.  
 
 
What happens if I chose not to participate?  
 
You may choose not to participate or withdraw at any moment along the course of the study 
without this carrying any consequence for you at work.   

The investigators commit to update you with any new information that arises along the course 
of the study, even if this may affect your decision to continue your participation.   
 
 
 
What happens if this research directly affects my health?   
 
While it is very unlikely that the intervention results in significant lesion, Pontificia Universidad 
Javeriana will cover all the medical expenditure resulting from a direct injury to your health 
related with the medication or study procedures. The study site will deliver any required 
treatment without any cost to you or to the health system. To cover all these potential costs, 
Pontificia 
Universidad Javeriana 
has 
purchased 
an 
insurance 
policy 
with 
La Previsora, Compañía de Seguros. Address of headquarters: Calle 57 # 9 -07, Bogotá, DC. PBX:
+571 348 5757 / Código Postal 52946.   
 
 
 What liability does my ARL (professional risks insurance company) have regarding any 
adverse events of damages resulting from my participation in the study?  
  
Since this is a study for which you are completely free to participate, neither you employer not
your ARL are responsible for the coverage of any risks directly associated with your 
participation in the study.  These risks are covered by the terms and mechanism described 
above. However, should you develop COVID-19, your participation does not limit or
exclude your ARL from the coverage of all disease associated expenditures.  
 
In case you need information or in case of emergency, you may contact the principal 
investigator, Dr. Sandra Valderrama to the number 3103322297. The principal investigator will
contact the Director of Clinical Research office of Hospital Universitario San Ignacio, Dr. 
Margarita 
Manrique 
to 
the 
phone 
number 
31534656992 or 
to 
the 
email mmmanrique@husi.org.co.  
 
If you have any doubt regarding the ethical issues of this research, which apply to all the study 
sites, you may contact the Institutional Review Board of the Pontificia Universidad Javeriana, 
Dr. Carlos Gómez-Restrepo (President) to the number 3208320 ext. 2770.  
 
By signing this from you DO NOT give up any legal right to receive medical care or accept 
payment for medical expenditures.  
AUTHORIZATION  
I have understood all explanations that have been given to me in a clear and simple 
language. The investigator has allowed me to put forward all my doubts and concerns regarding 
aims, methods, benefits, inconveniences, and prognosis associated with my participation in the 
study and they have been clarified. I received a copy of this document.   
 
By signing this document, I voluntarily consent to participating in the study “effectiveness of 
personal protective elements plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 

prevention of transmission of SARS-CoV-2 in previously healthy adult health care workers 
younger than 60 years.”.   
 
If you have any doubts regarding your participation in this study, you may contact the principal 
investigator, Dr. Sandra Valderrama to the number 3103322297, 5946161 ext. 6932 or
the president of the Institucional Review Board of Pontificia Universidad Javeriana, Carlos
Gómez-Restrepo, 3208320 ext. 2770, Carrera 7 No 40-62 Piso 8 Facultad de Medicina.    
Volunteer’s name  
 
 
Volunteer’s signature  
 
 
Type and number of identification  
 
 
Telephone  
 
 
Date  
 
 
 
Name of impartial witness 1  
 
 
Signature  
 
 
Type and number of identification  
 
 
Telephone  
 
 
Relationship with volunteer  
 
 
Date  
 
 
 
Name of impartial witness 2  
 
 
Signature  
 
 
Type and number of identification  
 
 
Telephone  
 
 
Relationship with volunteer  
 
 
Date  
 
 

 
Name of the research team member that 
carries-out the informed consent process  
 
Signature  
 
 
Type and number of identification  
 
 
Date   
 
 
Role in the study   
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Aappendix 5. Informed consent form in pregnancy  
  
  
  
MANAGEMENT OF CLINICAL RESEARCH  
  

    
  
 
  
  
INFORMED CONSENT IN CLINICAL 
RESEARCH PROJECTS  
 
 
 
 
 
 
 
 
       
  
                               
           
      
    
 

  
  
  
  
  
INTRODUCTION  
 
Volunteer’s code: ________________  
 
Since you became pregnant during your participation in the study effectiveness of personal 
protective elements plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 

prevention of transmission of SARS-CoV-2 in previously healthy adult health care workers 
younger than 60 years.” This document seeks to obtain your authorization to gather 
information regarding de development and outcome of you pregnancy and the health of 
your newborn.   
INFORMACIÓN GENERAL  
1. Why is this follow-up carried out?   
TDF/FTC is a medication classified as B in pregnancy, which means it belongs to a group of 
medicines for which there is no evidence fetal risk. The use of this medication is generally accepted 
during pregnancy. For instance, it is a drug of choice as part of the antiretroviral regimen for 
pregnant women infected with HIV, to avoid transmission of infection to the newborn.   
There is no evidence of teratogenicity in humans, which means it does not induce or increase the 
risk of malformations while administered during pregnancy. Nevertheless, there is evidence that it 
may cause fetal growth delay and reduction of fetal bone porosity while administered to monkeys 
at doses twice the dose used in humans during the first two months of pregnancy. In human studies, 
there is no proven association with these outcomes.   
 
In spite of being a drug with well established safety in pregnancy, we chose to carry out this follow 
up because at the beginning of the study you had a negative pregnancy test and now you have a 
positive pregnancy test, which means you pregnant and were exposed to TDF/FTC.  
2. How will be this follow-up done?   
 
After confirming your pregnancy we will gather information at the following moments:   
 
We will make phone calls every trimester and keep a record of the status of your pregnancy, 
maternofetal ultrasound and gestational age.   
 
We will contact you after birth to record the newborn’s sex, weight, length, cephalic 
perimeter, gestational age, delivery route and clinical status.   
 
By signing this document, you voluntarily accept telephone follow-up and review of your 
clinical records.   
 
3. 
What are the benefits of this follow-up?   
 
The only Benefit is to grant that you will have a follow up under the conditions described in question 
2, due to your exposure to TDF/FTC during pregnancy.  
 
 
Will there be confidentiality with management of my data?   
 
As described in the main informed consent form for the participation in the study, information 
contained in this follow-up will be protected according to law 1581 of 2012 (Habeas data) that 
applies for the treatment of personal data.   
 
All information gathered regarding your pregnancy and the health of you newborn will be kept 
confidential and will not be shared with any person or institution apart from investigators or 
the Institucional Review Board, without you prior authorization.   
 
Information obtained in this follow-up will be kept in the same manner as described in the main 
Informed Consent Format of the study, which was previously signed by you.   
 

 
Is there any financial obligation for me?   
 
You will incur in no financial obligation or expenditure while participating in this additional 
follow-up regarding your pregnancy.   
 
 
How long will be my participation in the study?  
 
Information will be collected along all your pregnancy up to birth.   
 
 
What happens if I chose not to participate?  
 
You may choose not to accept this follow-up or to withdraw your consent for follow-up at any time 
without this having any consequence for you or your newborn.   
   
4. 
What happens if this follow-up results in any direct injury or damage to 
my health?   
 
There is no potential medical risk associated with gathering this information by telephone.   
 
While it is very unlikely that you or your child suffer any damage derived from you taking TDF/FTC 
during pregnancy, Pontificia Universidad Javeriana will cover for any medical expenditures resulting 
from direct damage related with the investigational drug. The study site with deliver any necessary 
treatment to you or your newborn without you or the health system incurring in any expenditure. To 
cover for all these potential costs, Pontificia Universidad Javeriana has purchased an insurance 
policy with La Previsora, Compañía de Seguros, address: Calle 57 # 9-07, Bogotá, Colombia.  
 
Likewise, the policy will cover the costs of medical care and treatments in the case your newborn 
suffers any damage or disability resulting from participation in the study. The causality of the drug 
over these injuries or disabilities must be effectively established and demonstrated.   
 
In case you need information or in case of emergency, you may contact the principal 
investigator, Dr. Sandra Valderrama to the number 3103322297. The principal investigator 
will contact the Director of Clinical Research office of Hospital Universitario San Ignacio, Dr. 
Margarita 
Manrique 
to 
the 
phone 
number 
31534656992 
or 
to 
the 
email mmmanrique@husi.org.co.  
 
By signing this from you DO NOT give up any legal right to receive medical care or accept 
payment for medical expenditures.  
AUTHORIZATION  
I have understood all explanations that have been given to me in a clear and simple 
language. The investigator has allowed me to put forward all my doubts and concerns 
regarding aims, methods, benefits, inconveniences, and prognosis associated with my 
participation in this pregnancy follow up and they have been clarified.   
 

By signing this document, I voluntarily consent to be contacted with the purpose of 
gathering information about my pregnancy and its outcome, during pregnancy and after 
childbirth. Likewise, I authorize access to my personal information and that of my child.   
 
I received a copy of this document.   
 
If you have any doubts regarding your participation in this study, you may contact the 
principal investigator, Dr. Sandra Valderrama to the number 3103322297, 5946161 ext. 
6932 or the president of the Institutional Review Board of Pontificia Universidad Javeriana, 
Carlos 
Gómez-Restrepo, 
3208320 
ext. 
2770, 
Carrera 
7 
No 
40-
62 Piso 8 Facultad de Medicina.     
Volunteer’s name  
 
 
Volunteer’s signature  
 
 
Type and number of identification  
 
 
Telephone  
 
 
Date  
 
 
 
 
 
Name of couple/other parent of the minor   
 
 
Signature of 
couple/other parent 
of 
the 
minor   
 
 
Type and number of identification  
 
 
Telephone  
 
 
Date  
 
 
 
 
Name of impartial witness 1  
 
 
Signature  
 
 
 
Type and number of identification  
 
 

Telephone  
 
 
Relationship with volunteer  
 
 
Date  
 
 
 
 
 
 
Name of impartial witness 2  
 
 
Signature  
 
 
 
Type and number of identification  
 
 
Telephone  
 
 
Relationship with volunteer  
 
 
Date   
 
 
 
 
Name of the research team member that 
carries-out the informed consent process  
 
Signature  
 
 
Type and number of identification  
 
 
Date   
 
 
Role in the study   
 
 
 
  
  
  
  
  
  
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