Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan Cisgender Women
Phase: PHASE2
Conditions: HIV Infections
Sponsor: University of Washington

 
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STUDY PROTOCOL 
 
Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan Cisgender 
women 
 
 
The Women TAF-FTC Benchmark Study 
 
 
SPONSOR: 
University of Washington  
 
 
FUNDING SUPPORT: 
Gilead Sciences 
 
PHARMACEUTICAL SUPPORT: 
Study Drug Donated by Gilead Sciences  
 
 
 
PRINCIPAL INVESTIGATORS: 
Kenneth K. Mugwanya, MBChB, MS, PhD. 
Peter L. Anderson, Pharm.D. 
 
 
 
ClinicalTrials.gov: NCT05140954 
IND Status: Exempt 
 
 
 
Version 1.1 
15 August, 2022 
 
 
 
 
 

 
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The Women TAF-FTC Benchmark Study 
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TABLE OF CONTENTS 
LIST OF ACRONYMS .............................................................................................................................. 6 
PROTOCOL TEAM ROSTER .................................................................................................................. 8 
PROTOCOL SIGNATURE PAGE ............................................................................................................ 9 
PROTOCOL SCHEMA ........................................................................................................................... 10 
STUDY SUMMARY ................................................................................................................................ 12 
PROTOCOL ABSTRACT/SUMMARY .......................................................................................................... 12 
LAY SUMMARY ............................................................................................................................................... 13 
CONSORT DIAGRAM ..................................................................................................................................... 14 
1 
INTRODUCTION ............................................................................................................................. 15 
1.1 
Background and prior studies ................................................................................................................. 15 
1.1.1 
Disproportionate risk for HIV among African cisgender women ..................................................... 15 
1.1.2 
Evidence of TDF/FTC PrEP efficacy and relationship to adherence ................................................. 15 
1.1.3 
A new form of tenofovir for PrEP .................................................................................................... 15 
1.1.4 
Pharmacology of TFV and TFV-DP in African cisgender women ..................................................... 16 
1.2 
Problem statement ................................................................................................................................. 17 
1.3 
Justification ............................................................................................................................................. 17 
2 
STUDY OBJECTIVE AND DESIGN ............................................................................................... 17 
2.1 
Overall Hypothesis .................................................................................................................................. 17 
2.2 
Overall Objective ..................................................................................................................................... 17 
2.3 
Primary Objectives .................................................................................................................................. 17 
2.4 
Secondary Objectives .............................................................................................................................. 18 
2.5 
Study Design ............................................................................................................................................ 18 
2.6 
Enrollment Targets .................................................................................................................................. 19 
3 
STUDY POPULATION .................................................................................................................... 19 
3.1 
Inclusion Criteria ..................................................................................................................................... 19 
3.2 
Exclusion Criteria ..................................................................................................................................... 20 
3.3 
Study Setting ........................................................................................................................................... 20 
3.4 
Recruitment and Prescreening Process ................................................................................................... 21 
3.5 
Co-Enrollment Guidelines ....................................................................................................................... 21 
3.6 
Retention of Study Participants .............................................................................................................. 21 

 
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3.7 
Participant Withdrawal ........................................................................................................................... 22 
3.8 
Replacement of Study Participants ......................................................................................................... 22 
4 
STUDY PRODUCT .......................................................................................................................... 22 
4.1 
Study Product Formulation ..................................................................................................................... 22 
4.1.1 
Study product storage ..................................................................................................................... 23 
4.2 
Source of Study Product and Accountability ........................................................................................... 23 
4.2.1 
Study product dispensation ............................................................................................................ 23 
4.2.2 
Return and Destruction of Study Product ....................................................................................... 23 
4.3 
Assessment of Participant Adherence with Study Product/Intervention ............................................... 23 
4.4 
Concomitant Medications ....................................................................................................................... 23 
4.5 
Prohibited Medications ........................................................................................................................... 23 
4.6 
Precautionary Medications ..................................................................................................................... 24 
4.7 
Toxicity Management .............................................................................................................................. 24 
4.8 
HIV Seroconversion ................................................................................................................................. 24 
4.9 
Dose Modification ................................................................................................................................... 24 
5 
STUDY PROCEDURES .................................................................................................................. 24 
5.1 
Screening Procedures .............................................................................................................................. 24 
5.2 
Enrollment and Follow up Procedures .................................................................................................... 25 
5.2.1 
Dosing schedule and assessment of compliance ............................................................................ 25 
5.2.2 
Protocol pharmacology sampling visit schedule ............................................................................. 26 
5.2.3 
Clinical Evaluations/Procedures ...................................................................................................... 29 
5.3 
Procedures for participants identified as HIV infected and/or pregnant ................................................ 31 
6 
SAFETY MONITORING AND ADVERSE EVENT REPORTING ................................................... 31 
6.1 
Safety Monitoring ................................................................................................................................... 31 
6.2 
Clinical Data Review ................................................................................................................................ 32 
6.3 
Adverse Event Definition and Reporting ................................................................................................. 32 
6.4 
Relationship to Study Product ................................................................................................................. 32 
6.5 
Grading Severity of Events ...................................................................................................................... 32 
6.6 
Serious Adverse Event (SAE) ................................................................................................................... 33 
6.7 
Discontinuation of Study Medication ...................................................................................................... 33 
6.8 
Discontinuation of study drug with toxicity ............................................................................................ 33 
6.8.1 
AE Grades 1 or 2 .............................................................................................................................. 33 
6.8.2 
AE Grade 3 ....................................................................................................................................... 33 
6.8.3 
Grade 4 ............................................................................................................................................ 34 
6.8.4 
Creatinine Clearance ....................................................................................................................... 34 

 
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6.9 
Reporting Requirements for this Study ................................................................................................... 34 
6.10 
Social Impact Reporting .......................................................................................................................... 34 
7 
STATISTICAL CONSIDERATIONS ................................................................................................ 34 
7.1 
Review of Study Design ........................................................................................................................... 34 
7.2 
Study endpoints ...................................................................................................................................... 34 
7.3 
Data Analysis ........................................................................................................................................... 35 
7.3.1 
Primary outcomes ........................................................................................................................... 35 
7.3.2 
Secondary outcomes ....................................................................................................................... 35 
7.4 
Sample Size Considerations ..................................................................................................................... 36 
7.5 
Randomization and Blinding Procedures ................................................................................................ 36 
8 
HUMAN SUBJECTS CONSIDERATIONS ..................................................................................... 36 
8.1 
Ethical Review ......................................................................................................................................... 36 
8.2 
Informed Consent ................................................................................................................................... 37 
8.3 
Voluntary Participation ........................................................................................................................... 37 
8.4 
Potential Risks to Human Subjects .......................................................................................................... 37 
8.5 
Approaches to Minimize Risks ................................................................................................................ 39 
8.6 
Benefits. .................................................................................................................................................. 40 
8.7 
Treatment for Injury ................................................................................................................................ 40 
8.8 
Study Records .......................................................................................................................................... 41 
8.9 
Confidentiality ......................................................................................................................................... 41 
8.10 
Reimbursement ....................................................................................................................................... 41 
8.11 
Communicable Disease Reporting Requirements ................................................................................... 41 
8.12 
Reports of Sexual Abuse .......................................................................................................................... 41 
8.13 
Study Discontinuation ............................................................................................................................. 42 
9 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT .............................................. 42 
9.1 
Laboratory evaluations and specimen collections .................................................................................. 42 
9.2 
Specimen preparation, handling, and shipping ....................................................................................... 43 
9.3 
Specimen Storage and Possible Future Research Testing ....................................................................... 43 
9.4 
Quantification of drug concentrations .................................................................................................... 43 
9.5 
Biohazard Containment ........................................................................................................................... 43 
10 
ADMINISTRATIVE PROCEDURES ............................................................................................ 43 
10.1 
Study activation ....................................................................................................................................... 43 
10.2 
Study coordination .................................................................................................................................. 44 
10.2.1 
Data storage and management responsibilities .............................................................................. 44 
10.2.2 
Source Documents and Access to Source Data/Documents ........................................................... 44 

 
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10.2.3 
Data monitoring .............................................................................................................................. 44 
10.2.4 
Quality control and Quality assurance ............................................................................................ 44 
10.3 
Study monitoring ..................................................................................................................................... 44 
10.4 
Investigator’s Records ............................................................................................................................. 45 
10.5 
Use of Information and Publications ....................................................................................................... 46 
10.6 
Resource sharing and dissemination plan ............................................................................................... 46 
10.6.1 
Resource Sharing: ............................................................................................................................ 46 
10.6.2 
Data Sharing Plan ............................................................................................................................ 46 
10.6.3 
Collaborative research .................................................................................................................... 46 
10.6.4 
Dissemination plan .......................................................................................................................... 46 
10.6.5 
Presentations .................................................................................................................................. 47 
11 
TIMELINES .................................................................................................................................. 47 
12 
EXPECTED APPLICATION OF RESULTS ................................................................................ 47 
13 
STUDY LIMITATIONS ................................................................................................................. 48 
14 
REFERENCES ............................................................................................................................ 49 
15 
APPENDIXES— STUDY CONSENT FORM TEMPLATES ........................................................ 54 
Study Screening Informed Consent Form ............................................................................................... 54 
Study Enrollment Informed Consent Form .............................................................................................. 60 
 

 
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LIST OF ACRONYMS 
AE 
Adverse Event 
ART 
Anti-Retroviral Therapy 
BMI 
Body Mass Index 
CAB 
Community Advisory Board 
CBC 
Complete Blood Count 
CDC 
Centers for Disease Control and Prevention 
CLIA 
Clinical Laboratory Improvement Amendments 
CrCl 
Creatinine Clearance 
CRFs 
Case Report Forms 
Css 
Drug concentration at steady state 
CV 
Coefficient of Variation (SD/Mean) 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DBS 
Dried Blood Spots 
DNA 
Deoxyribonucleic acid 
DOT 
Directly Observed Therapy 
EAE 
Expedited Adverse Event 
FDA 
Food and Drug Administration 
FTC 
Emtricitabine 
FTC-DP 
Emtricitabine-diphosphate 
GCP 
Good Clinical Practices 
GEMS 
Global Evaluation of Microbicide Sensitivity 
GFR 
Glomerular Filtration Rate 
GT 
Gonorrhea Trichomoniasis 
HBAg 
Hepatitis B Antigen 
HBV 
Hepatitis B Virus 
HCT 
Hematocrit 
hDNA 
Human Deoxyribonucleic acid 
HIV 
Human Immunodeficiency Virus 
IEC 
Information, Education and Communication 
IoR 
Investigator of Record 
IRB 
Institution Review Board 

 
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KEMRI 
Kenya Medical Research Institute 
MEMS 
Medication Event Monitoring System 
MOH 
Ministry of Health  
MSM 
Men Who have Sex with Men 
NASCOP 
National AIDS & STI Control Programme 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PBMCs 
Peripheral Blood Mononuclear Cells 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PMTCT 
Prevention of mother-to-child transmission 
PPB 
Pharmacy and Poisons Board 
PrEP 
Pre-exposure prophylaxis 
PSRT 
Protocol Safety Review Team 
RBC 
Red Blood Cells 
RSC 
Regulatory Support Center 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
SSP 
Study Specific Procedures 
STI 
Sexually Transmitted Infection 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TAF 
Tenofovir Alafenamide Fumarate 
TDF 
Tenofovir Disoproxil Fumarate 
TDF/FTC 
Truvada® or Tenofovir Disoproxil Fumarate/Emtricitabine 
TFV 
Tenofovir 
TFV-DP 
Tenofovir-diphosphate 
TP 
Triphosphate 
UC 
University of Colorado 
UW 
University of Washington 
WB 
Whole blood 
WHO 
World Health Organization 
βHCG 
Beta-Human chorionic gonadotropin 
 
 
 

 
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PROTOCOL TEAM ROSTER 
Principal Investigator:  
Kenneth Mugwanya, MBChB, MS, PhD 
Assistant Professor, Global Health and Epidemiology 
University of Washington 
325 Ninth Avenue; Box 359927 
Seattle, WA 98104, USA 
Phone:206-520-3886 
Fax: 206 520 3831 
Email: mugwanya@uw.edu  
 
Co-Principal Investigator:  
Peter L. Anderson, PharmD 
Professor, Pharmaceutical Science 
University of Colorado Denver 
12850 E. Montview Blvd., V20-C238  
Aurora, CO 80045, USA 
Phone: 303 724 6128 
Fax: 303 724 6135 
Email: peter.anderson@ucdenver.edu  
 
Nelly R. Mugo, MBChB, M.Med, MPH. 
Senior Principal Clinical Scientist, Kenya Medical 
Research Institute, Nairobi, Kenya 
Research Associate Professor, University of 
Washington, Seattle, WA, USA 
Phone:254 067 2222561;  
Email: rwamba@uw.edu 
Role: Site Principal Investigator 
 
 
Elizabeth Irungu, MBChB, MPH, PhD. 
Research Scientist 
Kenya Medical Research Institute, Nairobi, 
Kenya 
Phone:2540672222561; 
Email: eirungu@uw.edu  
Role: Co-Investigator 
 
Catherine Kiptinness, B. Pharm, MPH 
Kenya Medical Research Institute, Nairobi, Kenya 
Phone:254 067 2222561 
Email: catherine@pipsthika.org  
Role: Pharmacist of Record and Site Study 
Coordinator. 
 
 
David Chege, BS. MLS, Dip. MLS 
Clinical Trials Research Laboratory Kenyatta 
National Hospital/Univ. of Nairobi 
Ground Floor Rm 7 and 8, Nairobi, Kenya 
Phone: 254725206216 
Email: dchege@pipsthika.org 
Role: Laboratory Manager 
Chohan Bhavna, MS, PhD 
Clinical Assistant Professor, Global Health 
University of Washington, Seattle, WA, USA 
Clinical Trials Research Laboratory Kenyatta 
National Hospital/Univ. of Nairobi 
Ground Floor Rm 7 and 8, Nairobi, Kenya 
Phone: 206-773-9901 
Email: bchohan@u.washington.edu 
Role: Laboratory Director 
Clare E. Brown, PhD 
University of Washington 
325 Ninth Avenue; Box 359927 
Seattle, WA 98104, USA 
Phone:206-520-3886 
Fax: 206 520 3831 
Email: brownce@uw.edu 
Role: Research Manager 
 
 
 
 

 
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Version 1.0 August 15, 2021 
 
ClinicalTrials.gov: NCT05140954  
 
PROTOCOL SIGNATURE PAGE 
 
Funding Support by: 
Gilead Sciences 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable protocol-
related documents. The signature below constitutes the approval of this protocol and the attachments, 
and provides the necessary assurances that this trial will be conducted according to all the stipulations 
of the protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable U.S. Federal regulations and International Conference on 
Harmonisation guidelines. 
 
 
__________________________________ 
Name of Site Investigator of Record 
 
__________________________________  
_________________________________ 
Signature of Site Investigator of Record 
 
Date  
 
 
 

 
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PROTOCOL SCHEMA 
Full Title: 
Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in African 
Cisgender women 
Short Title:            The Women TAF-FTC Benchmark Study 
Clinical Phase:      IIb 
Principal Investigators: Kenneth K. Mugwanya, MBChB, PhD, Peter L. Anderson, Pharm.D. 
Purpose: 
To assess the safety and define blood and tissue benchmark concentrations of 
Tenofovir (TFV) and Tenofovir diphosphate (TFV-DP) in cisgender women using 
directly observed tenofovir alafenamide (TAF)-emtricitabine (TAF-FTC) PrEP. These 
data will help guide accurate interpretation of efficacy results obtained in HIV 
prevention trials and programs in cisgender women. 
Study design: 
An open-label, randomized, three-arm, directly observed therapy, pharmacokinetics 
study. HIV-uninfected non-pregnant cisgender women will be randomly assigned 
1:1:1 to 1 of 3 dosing frequencies of DOT TAF-FTC PrEP: 2, 4, or 7 doses/week to 
help differentiate poor and modest adherence from perfect adherence. Drug 
concentrations in blood, cervico-vaginal fluid, and tissue will be measured during the 
study. The frequency of adverse events will be described. 
Study population: The study will enroll 18-30 years old HIV uninfected, non-pregnant Kenyan cisgender 
women at low risk of HIV. 
Study site: 
The Kenya Medical Research Institute-Thika Research Site, Thika, Kenya  
Study regimen: 
Volunteers will receive 25 mg TAF/ 200mg FTC according to the dosing regimens 
outlined in the study design.  
Study duration: 
The study will last for up to approximately 18 weeks for each participant. Recruitment, 
enrollment, and follow up will continue for approximately 2 years.  
Hypothesis: 
TFV and TFV-DP dose-response thresholds from DOT TAF-FTC PrEP dosing for 
cisgender women will be defined but will differ from thresholds defined for TDF-FTC 
PrEP 
Primary objectives: 
1. To describe the safety of TAF-FTC-based PrEP in HIV-uninfected cisgender women.  
2. To define cisgender women-specific expected blood concentrations and dose-
proportionality for TFV-DP in DBS and PBMCs using directly observed TAF-FTC 
therapy at 2, 4, 7 doses per week.  
3. To establish a model to predict adherence rate to TAF-FTC by level of TFV-DP in 
DBS for cisgender women. 
Secondary objectives: 
1. To define the expected concentrations and dose-proportionally for TFV-DP in 
PBMCs and vaginal tissue 

 
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2. To examine relationships among drug concentrations in plasma, WB, DBS, and 
PBMCs. 
3. To determine the influence of biological variables (e.g. mean corpuscular volume 
and HCT, age, weight, sex) on drug concentrations.  
4. To compare drug concentrations in DBS from fingerstick versus drug concentrations 
in DBS transferred from blood tubes. 
 
Primary outcomes: Benchmark concentrations of TFV-DP from TAF in DBS and PBMCs, and the 
dosing frequency (i.e., doses per week) required to generate them.  
 
 
 

 
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STUDY SUMMARY 
PROTOCOL ABSTRACT/SUMMARY 
Pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil 
fumarate (TDF) is a potent HIV prevention method for cis- and transgender men and gender women. 
Efficacy is highly dependent on adherence. Pivotal studies that combined clinical epidemiology and 
pharmacology defined thresholds for PrEP protection in cisgender men who have sex with men (MSM) 
that have been key to PrEP promotion and development of new PrEP agents. For African cisgender 
women at risk for HIV, a priority group due to disproportionately high incident HIV infections, variable 
adherence in PrEP clinical trials and limited pharmacokinetics data have resulted in lack of clarity about 
levels of PrEP use required for HIV protection. A new form of tenofovir, tenofovir alafenamide fumarate, 
co-formulated with emtricitabine (TAF-FTC) or Descovy® has recently been approved by the U.S. Food 
and Drug Administration for PrEP use in cisgender men and transgender women. However, Descovy® 
is not indicated in at risk cisgender women because its safety and effectiveness in this population has 
not been evaluated. Studies are now planned or ongoing in African cisgender women to evaluate TAF-
FTC for PrEP. Tenofovir-diphospate (TFV-DP) in dried blood spots was critical for interpreting Descovy® 
study outcomes in the DISCOVER trial, and will again be essential for the planned studies to evaluate 
the effectiveness of Descovy® for PrEP in cisgender women. Thus, clear knowledge of African cisgender 
women-specific adherence-concentration benchmark for TAF-FTC relationship is essential to define 
success of these studies. To date, no study has evaluated safety and directly observed expected TAF-
FTC PrEP concentrations in African cisgender women with varying frequency of PrEP adherence. TAF 
efficiently achieves higher concentrations within lymphoid cells while attaining lower TFV concentration 
in plasma compared to TDF. This creates potential advantages of TAF for PrEP, as the higher TFV-DP 
in lymphoid cells may confer high activity, whereas the lower plasma TFV concentrations may improve 
markers of bone and renal changes compared with TDF. Although the clinical significance of these 
marker changes is unknown, it is thought that TAF may exhibit improved long-term safety compared with 
TDF. We will conduct an open-label, randomized, three-arm, directly observed dosing pharmacokinetics 
study of TAF-FTC PrEP in African cisgender women. The primary objectives are: 1) To assess the 
safety of TAF-FTC PrEP in cisgender women. 2) To define the cisgender women-specific expected 
blood concentrations and dose-proportionality for TFV-DP in DBS and PBMCs using directly 
observed TAF-FTC therapy at 2, 4, 7 doses per week. 3) To establish a model to predict adherence 
rate to TAF-FTC by level of TFV-DP in DBS for cisgender women. HIV-uninfected non-pregnant 
cisgender women will be randomly assigned to 1 of 3 dosing frequencies of directly observed therapy 
(DOT) TAF-FTC PrEP: 2, 4, or 7 doses/week, to represent poor, modest, and perfect adherence, 
respectively. The study will enroll up to 54 18-30 years old HIV uninfected cisgender women at low risk 
of HIV at Thika site in Kenya. The proposed study will be the first to define TAF-PrEP adherence-blood 
concentration thresholds for African cisgender women, a priority population for HIV prevention. The 
findings will guide accurate interpretation of safety, adherence, and efficacy of planned or ongoing HIV 
prevention trials in African cisgender women. 
 

 
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LAY SUMMARY 
Title:  Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan Cisgender 
women 
Lay title: A project to assess the safety and define the expected blood levels of PrEP medications in 
cisgender women derived from varying number of PrEP doses taken per week. 
Background: 
African cisgender women are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) is an 
effective HIV prevention strategy, but variable adherence in PrEP clinical trials among African cisgender 
women and limited pharmacokinetics data have resulted in a lack of clarity about the degree of PrEP use 
required for HIV protection in cisgender women. For cisgender men who have sex with men, the STRAND 
and DOT-DBS studies defined the adherence levels to PrEP medication and expected drug 
concentrations arising from varying directly observed therapy (DOT) doses per week. Those thresholds 
are today being applied to studies of African cisgender women taking PrEP, and cisgender women-
specific levels associated with HIV prevention have never been defined. However, recent data from large 
PrEP studies we have done among African cisgender women ─ including the Partners PrEP Study and 
Partners Demonstration Projects conducted at Thika site ─ suggest those these levels may not reflect 
the pharmacology of cisgender women in African settings. In these studies in African populations, 
however, PrEP dosing was not directly observed therapy; no study has established expected PrEP 
concentrations in African cisgender women with varying frequency of PrEP adherence. Thus, there is an 
urgent need to define the frequency of adverse events, adherence and expected blood concentrations of 
PrEP medications in cisgender women.  
What questions are we trying to answer? 
We seek to assess the safety and define the expected blood levels of PrEP medications (tenofovir) for 
cisgender women taking directly observed oral PrEP therapy to understand the frequency of PrEP dosing 
associated with HIV protection in cisgender women. Cisgender women will be randomly assigned to 
receive varying frequency of weekly PrEP doses and followed for up to 18 weeks.  
Where is the project taking place? 
The study will take place in Thika, Kenya.  
How will the project benefit society? 
We propose to conduct the first study of oral PrEP adherence-concentration thresholds in Kenyan 
cisgender women, a population facing significant burden of incident HIV infection. Knowledge gained 
from the proposed study will include the frequency of adverse events, key blood concentrations of PrEP 
medications, and the frequency of pill taking required to achieve those concentrations in cisgender 
women. The results of this work will have immediate implications for PrEP programs, HIV prevention, 
and the global HIV prevention field. 
 
 
 
 
 

 
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CONSORT DIAGRAM 
 
 
  

 
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1 
INTRODUCTION 
1.1 
Background and prior studies 
Adherence is critical to therapeutic success for HIV treatment and pre-exposure prophylaxis of new HIV 
infections (PrEP). This section describes HIV risk in African cisgender women, TDF/FTC effectiveness 
and the importance of adherence, the lack of progress in quantifying adherence clinically, the high 
promise of TFV-DP in DBS as a novel adherence measure, and considerations for implementing 
adherence monitoring into clinical care.   
1.1.1 Disproportionate risk for HIV among African cisgender women 
More than 600 000 new HIV infections occur annually among young African cisgender women1, with 
incidence rates often double or more than those among their cisgender male age-mates2-4. A recent 
clinical trial in eastern and southern Africa (the ECHO Study)5 that evaluated the risk of HIV acquisition 
in HIV-negative cisgender women who used three common contraceptive methods found that HIV 
incidence among sexually active cisgender women was alarmingly high ─ on average nearly 4% ─ with 
higher rates of HIV infection for cisgender women <25 years irrespective of the contraceptive method. 
These recent results emphasize that HIV remains a significant personal risk and public health challenge 
for many cisgender women in African countries. 
1.1.2 Evidence of TDF/FTC PrEP efficacy and relationship to adherence 
FTC/TDF PrEP is a highly efficacious and safe strategy for reducing HIV risk among cisgender men and 
transgender women who have sex with men 6, heterosexual cis- and transgender men and women7, 8, 
and injection drug users9, and is now recommended as a prevention option for all persons at high risk for 
acquiring HIV10-12. There was variation in HIV protection across first generation FTC/TDF PrEP trials 
(Figure 1)13, and pharmacokinetics measurements as markers of adherence have transformed our 
understanding of FTC/TDF PrEP adherence and efficacy. In the Partners PrEP Study, which included 
1,785 East African cisgender women with a mutually disclosed HIV-infected partner, PrEP efficacy 
among cisgender women was 66% for TDF and 
71% for FTC/TDF PrEP vs placebo7, and the 
protective effect was consistent in subgroups of 
cisgender women at high risk for HIV 
acquisition14. In the TDF2 study in Botswana, 
PrEP efficacy among cisgender women was 
49%, but interpretation was limited by the small 
sample size8. However, the enthusiasm for 
PrEP use in cisgender women faltered after the 
FEM PrEP and VOICE trials failed to 
demonstrate efficacy15, 16. While there were 
initially several potential explanations for the 
failure of PrEP in these two trials, including behavior and biologic factors, the consensus settled on poor 
adherence17. 
1.1.3 A new form of tenofovir for PrEP  
The DISCOVER trial evaluated the safety and efficacy tenofovir alafenamide fumarate co-formulated with 
emtricitabine (F-TAF) (Descovy®) for PrEP use in cisgender men and transgender women18. This 
randomized, double-blind multinational trial, enrolled 5,387 HIV-negative cisgender men and transgender 
women who have sex with men and were at risk of HIV-1 infection to  compare once daily Descovy® to 
Truvada (emtricitabine, tenofovir disoproxil fumarate, 200 mg/300 mg)19. Following the trial, Descovy® 
was approved by the U.S. Food and Drug Administration for PrEP use in cisgender men and transgender 
women18. However, Descovy® is not yet indicated in at risk cisgender women because the effectiveness 
in this population has not been evaluated. Studies are now ongoing in African cisgender women to 
Figure 1. Graphical presentation how PrEP efficacy varied by adherence across 
PrEP trials (credit AVAC) 

 
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evaluate F-TAF (TAF-FTC) for PrEP. For persons with HIV, Descovy® has been approved for FDA for 
treatment of HIV in combination with other antiretroviral drugs since 201620. 
In the original TDF prodrug form, tenofovir was liberated during hepatic first pass by esterases and 
phosphodiasterases leading to high tenofovir concentrations in the plasma compartment21. TAF, on the 
other hand, largely survives first pass intact allowing it circulate in blood from which it efficiently enters 
lymphoid cells where it liberates TFV through cathepsin A21. This creates potential advantages of TAF 
for PrEP, as the higher TFV-DP in lymphoid cells may confer high activity, whereas the lower plasma 
TFV concentrations may improve markers of bone and renal changes compared with TDF. Although, the 
clinical significance of these marker changes is unknown, it is thought that TAF may exhibit improved 
long-term safety compared with TDF22. 
DISCOVER used tenofovir diphosphate concentrations (TFV-DP) in DBS to determine adherence to 
FTC/TDF and TAF-FTC. To interpret adherence, adherence benchmarks were determined in cisgender 
men and cisgender women in the USA through the DOT-DBS and TAF-DBS studies using directly-
observed therapy (DOT). These benchmarks were determined using 2, 4, and 7 DOT doses/ week, has 
and have proven to be critical for understanding PrEP adherence and efficacy in cisgender men and 
transgender women. Taken together, TAF is a promising new pro-drug for treatment and as PrEP for 
prevention of HIV infection, but studies are needed in cisgender women to determine if TFV-DP in DBS 
will provide the same adherence assessments for TAF as it did for TDF. This due to differing cell 
pharmacology between TDF and TAF, meaning that TFV-DP in DBS described above from TDF cannot 
be extrapolated to TAF. Ultimately, we believe that TFV-DP in DBS will have a similar half-life and 
accumulation as TDF, and will thus provide similar “dose-response” information for TAF-based PrEP, but 
studies are needed to define TFV-DP in DBS following F-TAF dosing. This protocol is designed to fill that 
need. The results from this protocol will be used to interpret drug levels and DBS testing that has been 
incorporated into planned or ongoing TAF-FTC PrEP studies in African cisgender women, where 
adherence monitoring is a key outcome. 
1.1.4 Pharmacology of TFV and TFV-DP in African cisgender women 
For African cisgender women at risk for HIV, variable adherence in PrEP clinical trials and limited data 
for TFV-DP in DBS have resulted in lack of clarity about levels of PrEP use required for HIV protection. 
Indeed, the absence of robust pharmacokinetics data for cisgender women, particularly studies that link 
adherence to expected concentrations, helped prevent the TAF-FTC indication for HIV prevention to be 
extended to cisgender women. Recent data from large FTC/TDF PrEP studies we have done among 
cisgender women23, 24, including the IMPAACT 2009 
Study 25, indicate that the pharmacology of FTC/TDF 
in DBS in cisgender women in African settings may 
be different from that in USA settings, in general and 
particularly 
in 
pregnancy 
where 
TFV-DP 
concentrations may be reduced by 30-40%23, 24. 
With NIH funding, we will define adherence 
benchmarks and dose-proportionality for TFV-DP in 
DBS (and PBMCs) among Kenyan cisgender 
women using directly observed F-TDF therapy at 2, 
4, 7 doses per week.  
TFV-DP in DBS was critical for interpreting 
Descovy® study outcomes in the DISCOVER trial, and will again be essential for the planned studies to 
evaluate the effectiveness of Descovy® for PrEP in cisgender women. Interpretation of reductions in HIV 
infection rates attributable to TAF-FTC and defining success of these studies will greatly depend, in great 
part, on accurate understanding of the degree of adherence/non-adherence to TAF-FTC and FTC/TDF 
Figure 2: Concentrations among Cisgender women with 100% Adherence by 
MEMS (Pyra, Anderson et al AIDS 2018) 
 
1250 fmol/punch: US male–derived TFV-DP concentration threshold for 100% 
adherence (7 doses/week) 

 
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in the study population. Thus, clear knowledge of African cisgender women-specific adherence-
concentration benchmark relationship is essential to define success of these studies, and this study will 
directly address this need. Using our combined complementary expertise in HIV prevention research in 
African women and antiretroviral pharmacology, we will define specific adherence-concentration 
benchmarks for TAF-FTC in African cisgender women that will help interpretation of ongoing F/TAF 
(Descovy®) PrEP studies in cisgender women. 
1.2 
Problem statement 
TAF-FTC (Descovy®) is a promising new pro-drug for treatment and prevention of HIV infection and is 
approved by the U.S18. Food and Drug Administration as HIV PrEP to reduce the risk of HIV infection 
from sex in at-risk adult and adolescent cisgender MSM and transgender women weighing at least 35kg18. 
However, the absence of robust pharmacokinetics data for cisgender women, in particular studies that 
link adherence to expected drug concentrations, prevented the extension of the TAF-FTC indication for 
HIV prevention to cisgender women. Thus, studies are needed in cisgender women to determine if TFV-
DP levels in blood will provide the same adherence assessments for TAF as it did for TDF. This study 
will address this issue, and the study results from this  will be used to interpret safety and drug levels and 
DBS testing that has been incorporated into ongoing TAF-FTC PrEP studies in African cisgender women, 
where adherence monitoring is a key outcome. 
1.3 
Justification  
TFV-DP in DBS was critical for interpreting Descovy® study outcomes in the DISCOVER trial, and was 
critical for understanding PrEP efficacy for Truvada in cisgender men and transgender women. As 
described above, TAF may improve upon TDF for HIV prevention in both efficacy and safety, and there 
is a need to define cisgender women-specific adherence benchmarks. To interpret adherence, adherence 
benchmarks were determined in cisgender men and cisgender women in the USA through the DOT-DBS 
and TAF-DBS studies using DOT which has proven to be critical for understanding PrEP adherence and 
efficacy in cisgender men and transgender women. Because the cell pharmacology for TDF and TAF 
differs, and TFV-DP benchmarks defined TDF in cisgender men and transgender women cannot be 
extrapolated to TAF, cisgender women-specific benchmark concentration thus need to be defined. 
Ultimately, we believe that TFV-DP in DBS will have a similar half-life and accumulation as TDF thus 
providing similar “dose-response” information for TAF-based PrEP, but studies in cisgender African 
women ─ who are disproportionately affected by HIV and thus a priority target for PrEP ─ are needed to 
define safety and TFV-DP in DBS following TAF-FTC dosing in cisgender women.  
2 
STUDY OBJECTIVE AND DESIGN 
2.1 
Overall Hypothesis 
Safety and TAF-FTC dose-response thresholds from DOT dosing for cisgender women will be defined 
but will differ from TDF-FTC thresholds defined for cisgender women. The comparator thresholds from 
TDF-FTC  PrEP will be obtained from an ongoing contepreneous DOT dosing study for cisgender women 
at same site. 
2.2 
Overall Objective 
The central objective of this proposal is to describe the safety and expected blood and tissue adherence-
concentration benchmarks for DOT TAF-FTC PrEP for Kenyan cisgender women. 
2.3 
Primary Objectives 
1) To describe the safety of TAF-FTC-based PrEP in HIV-unifected cisgender women.  
2) To define the cisgender women-specific expected blood concentrations and dose-
proportionality for TFV-DP in DBS and PBMCs in cisgender women using directly observed 
TAF-FTC therapy at 2, 4, 7 doses per week.  

 
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3) To establish a model to predict adherence rate to TAF-FTC by level of TFV-DP in DBS for 
cisgender women. 
2.4 
Secondary Objectives 
1) To define the expected concentrations and dose-proportionally for TFV-DP in PBMC and 
vaginal tissue 
2) To examine relationships among drug concentrations in plasma, WB, DBS, and PBMC. 
3) To determine the influence of biological variables (e.g., HCT, age, weight, sex, metabolites 
from metabolomics, and genetic variability in drug transporter/clearance proteins) on drug 
concentrations.  
4) To compare drug concentrations in DBS from fingerstick versus drug concentrations in 
DBS transferred from blood tubes. 
2.5 
Study Design 
This is an open-label, randomized, three-arm, directly observed therapy, pharmacokinetic study of TAF-
FTC PrEP among low-risk HIV-uninfected non-pregnant cisgender women. HIV-uninfected non-pregnant 
cisgender women at 
low risk for HIV will be 
randomly assigned to 1 
of 3 dosing frequencies 
of DOT TAF-FTC PrEP 
(Figure 3): 2, 4, or 7 
doses per week to help 
differentiate poor and 
modest from perfect 
adherence (Figure 3).  
Enrollment 
will 
continue until 54 non-
pregnant 
evaluable 
participants 
(i.e., 
participant 
with 
completed 
data 
on 
dosing 
and 
PK 
samples) are enrolled. 
– Group #1: “7 doses 
per week or Perfect Adherence arm”— cisgender women will receive a single tablet of co-formulated 
25 mg TAF/ 200mg FTC once daily (7 doses per week).  
– Group #2: “4 doses per week or Moderate Adherence arm” — cisgender women will receive a single 
tablet of co-formulated 25 mg TAF/ 200mg FTC tablet on Monday, Tuesday, Thursday, Friday. 
– Group #3: “2 doses per week or Poor Adherence arm” — cisgender women will receive a single 
tablet of co-formulated 25 mg TAF/ 200mg FTC tablet on Monday and Tuesday 
Justification for non-daily dosing of PrEP groups:  
In this study we propose to randomize cisgender women to non-daily dosing of PrEP (2, or 4 doses per 
week). The non-daily dosing is needed to investigate and demonstrate dose proportionality of TFV and 
TFV-DP concentrations. The adherence-concentration thresholds derived from this dosing frequency will 
help guide appropriate interpretation of adherence to TAF-based PrEP in clinical studies and 
implementation programs of PrEP. To minimize the risk of HIV infection in the non-daily dosing groups, 
as detailed in the eligibility section, only non-pregnant cisgender women at low HIV risk based on Kenya 
Figure 3 :  Schema for directly observed TAF-FTC PrEP dosing and pharmacokinetics sampling  
 

 
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guidelines will be enrolled and participants will receive a full package of HIV prevention, including risk 
reduction counseling, condoms and STI treatment at each visit. We will also perform monthly HIV testing. 
We will closely monitor the frequency of adverse events, including emergent HIV serocoversion 
(expected to be very rare) between groups. 
2.6 
Enrollment Targets 
A cohort of up to 54 cisgender women who meet the inclusion and exclusion criteria described in Section 
3 below will be enrolled at the KEMRI Thika Research Site, in Thika, Kenya. Enrollment will continue until 
54 evaluable cisgender women are enrolled who agree to use PrEP at the Enrollment visit. Cisgender 
women who accept PrEP will be randomized 1:1:1: 2, 4, or 7 DOT doses per week to help differentiate 
poor and modest from perfect adherence.  
3 
STUDY POPULATION  
We will enroll a novel cohort of up to 54 healthy, HIV-uninfected non-pregnant Kenyan cisgender women 
volunteers 18-30 years to establish benchmark adherence-concentration thresholds for TAF-based 
PrEP. Participants will be selected for the study according to the criteria in Sections 3.1 and 3.2. They 
will be recruited, screened, and enrolled as described in Section 3.4.  
3.1 
Inclusion Criteria 
This study will enroll young Kenyan cisgender women (aged 18-30 years old). Cisgender women bear 
the greatest burden for HIV infection; thus, the study will focus solely on cisgender women. HIV incidence 
is greatest in younger cisgender women ages 15-24, as is interest in accumulating PrEP data from Kenya. 
Thehe age limitation on enrollees into the study reflects that clinical and epidemiologic need. Enrollment 
criteria will be finalized at the time of protocol development to account for any updates to Kenyan national 
guidelines, but the central clinical criteria are as follows: 
 
For all cisgender women 
- 
Age ≥18 and ≤30 years old. 
- 
Willing to undergo urine pregnancy tests. 
- 
Has understood the information provided and has provided written informed consent before 
any study-related procedures are performed. 
- 
HIV uninfected based on negative HIV rapid tests, according to Kenyan national algorithm. 
- 
Normal renal function (estimated glomerular filtration rate >60 mL/min). 
- 
Hepatitis B surface antigen negative. 
- 
No active, clinically significant medical or psychiatric conditions that, in the opinion of the 
investigators, would interfere with study participation . 
- 
Lack of severe anemia (Hemoglobin >10 g/dL). 
- 
Willing to use DOT and come to clinic frequently for DOT PrEP for at least 10 weeks. 
- 
Willing to have home visits for follow up. 
- 
Has access to an active smartphone to allow off-site observation of dosing if unable to come 
to the clinic, or, as determined by the study staff, the participant resides in a close enough 
location  to the clinic to permit a home visit if unable to come to the clinic. That is, potential 
participants without a smatphone may be enrolled in the study if investigator determines that 
the participant resides within reasonable distance from the clinic for a home visit in the case 
of a missed clinic visit. 
- 
Intention to stay within the study site’s catchment area for at least 10 weeks. 
- 
Resides or works in catchment area with high speed internet coverage to permit video 
streaming. 
- 
Not pregnant or breast feeding. 
- 
Willing to use effective contraception during the study period. 
- 
At low risk for HIV. In Kenya, national guidelines define substantial risk for HIV and 
recommend PrEP be an option for individuals reporting: partner of HIV-infected person not on 

 
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ART or on ART for <6 months, >1 partner of unknown status, transactional sex, recent STI, 
recurrent PEP use, inconsistent condom use, or injection drug use. So, non-pregnant 
cisgender women reporting any of these factors will not be eligible for the study but will be 
linked for PrEP at clinic of choice including at Thika Site itself. 
- 
Willing to be randomized to non-daily PrEP and to come to the clinic frequently for DOT PrEP. 
- 
Willingness and ability to be abstinent for at least 7 days after each vaginal biopsy visit. 
 
3.2 
Exclusion Criteria 
For all cisgender women 
– Inability to give informed consent 
– Positive screening HIV+ as determined by standard rapid serologic assays or suspected acute 
HIV infection in the opinion of the clinician. (Example signs and symptoms of acute HIV 
infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, 
diarrhea, pharyngitis, rash, night sweats, and cervical or inguinal adenopathy.) 
– Positive HBV surface antigen test at screening. 
– Calculated creatinine clearance <60 ml/min. 
– Any laboratory value or uncontrolled medical conditions that, in the opinion of the 
investigators, would interfere with the study conditions such as, heart disease and/or cancer. 
– Prohibited concomitant medications are: investigational agents (within 30 days of enrollment), 
aminoglycosides, 
ganciclovir/valganciclovir, 
chronic 
high-dose 
acyclovir/valacyclovir 
(>800mg acyclovir or >500mg valacyclovir for >7 days), cyclosporine, amphotericin B, 
foscarnet, and cidofovir, and products with same or similar active ingredients as the study 
medications including TAF®, TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, 
VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and 
tenofovir, respectively.  
– Current or past use of PrEP (pre-exposure prophylaxis). 
– Not willing to have home visits. 
– Pregnant or plan to become pregnant in the next 6 months or unwillingness to use birth control 
. 
– Currently breastfeeding. 
– High risk of HIV infection (for example: sexually active with an HIV infected partner; engages 
in condomless intercourse with HIV-infected partners or partner of unknown status during the 
study; exchanges sex for money, shelter, or gifts; active injection drug use or during the last 
12 months; newly diagnosed sexually transmitted infections in last 6 months.  
3.3 
Study Setting 
The proposed work will take place in Thika, Kenya. The site has extensive experience conducting large 
biomedical and PK studies7, 26-35 and has a long-standing relationship with local public health authorities, 
HIV prevention advocates, and community leaders. Over the past decade, the Thika site has established 
a multi-disciplinary team focused on HIV prevention research (more than a dozen projects currently) and 
on provision of clinical care, including clinical studies involving follow up of pregnant cisgender women. 
The Thika site is a center of excellence for PrEP in Kenya and leads PrEP technical assistance to other 
clinics as part of Kenya national PrEP scale-up. As stated in the background section, the Thika site 
conducted the DOT PrEP PK study in breastfeeding cisgender women (see Figure 3)26, achieving 100% 
retention. 

 
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3.4 
Recruitment and Prescreening Process 
We will enroll a novel cohort of up to 54 evaluable non-pregnant, healthy, HIV-uninfected adult cisgender 
women volunteers. The experienced community outreach team at the study site in Thika employs 
community-based mobilization strategies, including working with the neighboring Thika District Hospital 
to identify pregnant cisgender women, 
engaging community health volunteers, 
gate keepers, peer to peer mobilization, 
youth peer providers and ambassador 
models, use of printed and electronica IEC 
materials, social media (WhatsApp and 
Facebook), radio talk shows in English and 
Kiswahili, active participation in local social 
events 
for 
information 
sharing, 
and 
partnering with learning institutions to give health talks and to provide study related information. The 
methods for recruitment proposed in this study are similar to those that were successfully used to conduct 
the pharmacokinetic study of PrEP in Breastfeeding cisgender women at the Thika site. From these 
strategies, we will identify those that are highest yielding and shift focus to primarily rely on them. The 
outreach team at PHRD is well-suited to develop innovative recruitment methods and collaborate with 
local partners to ensure that we achieve the accrual rate needed and enroll cisgender women who are 
highly dedicated to research procedures. The Thika team has >10 years of experience of conducting 
clinical trials, including in populations of cisgender women (Table 1). In many of the studies we have 
conducted, the Thika site has achieved the highest recruitment and data quality site compared to others 
in multisite/multinational studies – for example, in the Partners PrEP Study clinical trial of PrEP, and the 
MPYA Study. We will replicate and extend all of those previously proven recruitment strategies for this 
study. 
3.5 
Co-Enrollment Guidelines 
Participants in this study should not take part in any concurrent research studies that use drugs or medical 
devices while on follow up. Co-enrollment in observational or other studies may be allowable with 
approval of the site IoR or designee. Previous participation in the placebo arm of an HIV vaccine trial 
may be allowable with approval of Co-Chairs. 
3.6 
Retention of Study Participants 
For this DOT pharmacokinetics study, high retention begins with the exclusion of participants who 
indicate a high likelihood of travel outside of the study area, who appear to lack dedication to the research 
process, or who may experience personal challenges with compliance with study visits. We will follow 
usual Kenyan clinical practices for notifying participants of their study follow-up visits, which include 
sending participants reminders via SMS messaging and telephone calls. In addition, an extensive tracing 
record at the time of study entry will be completed by a trained research staff member and will be used 
to trace participants who miss visits; the experienced community outreach team has established methods 
for successful participant tracing. As detailed in the Introduction Section, the Thika Site successfully 
recruited lactating cisgender women (and their infants, half <13 weeks of age) into a similar DOT PrEP 
PK study previously, achieving 100% retention for breastfeeding-month infant pairs and sample 
collection. The following approaches will be used to promote compliance and to achiev planned evaluable 
enrollment with pharmacokinetic sample collection. 
Medication calendar: At study enrollment, subjects will be given a calendar for study visit 
appointments, dosing schedules, and to record unsolicited adverse events. For those interested 
and willing, visit schedule and reminders will be added to the calendar on their smartphones. 
Table 1:  Studies involving pregnant cisgender women at Thika 
Study and funding 
Number of cisgender 
women enrolled 
Partners PrEP (BMGF) 
112 
Partner Demo Project 
(R01MH0559907) 
332 
SCIP (R00HD076679) 
74 
MPYA (R01MH109309) 
175 
NuvaRing (R01HD077872) 
122 
GHS (CDC U48DP005013) 
400 

 
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Video streaming and phone reminders: Flexible clinic scheduling will be available to promote 
high rates of follow-up and compliance and to minimize participant’s burden. Video live streaming 
services via social media (e.g., WhatsApp, Skype, etc.) will be employed; only cisgender women 
with an active smart phone will be enrolled into the study to permit offsite observation of required 
DOT PrEP doses if needed. Use of live streaming will be supported with provision of weekly 
data/internet bundles consistent with the local IRB regulation. Remote DOT via video streaming 
is intended to increase compliance as well as minimize participant burden. Enrolled participants 
will receive a reminder message (sent via text message or phone call) the morning of every 
scheduled study visit. A one-month supply of back-up medication will be provided to participants 
at study enrollment to be used if the participant is unable to complete a visit at the clinic; all doses 
taken offsite will be directly observed by study staff via live video streaming on smart cell phone 
or computer via WhatsApp. For DOT doses taken via video streaming, participants will be asked 
to open their mouth afterwards to confirm swallowing.and  
Home visits: We will conduct home visits for patients unable to attend their scheduled clinic visits 
or procedures in order to promote compliance with study procedures. During home visits, study 
staff may conduct study procedures e.g., observing of dose taking or collection of study samples 
(blood, urine, hair) where applicable. Any offsite collection of study sample will follow the same 
safety standards followed at the clinic. For this short-term intensive pharmacokinetics study 
where complete DOT compliance is pivotal for primary outcome measurement, only 
cisgender women who consent for home visits will be enrolled. 
3.7 
Participant Withdrawal 
Regardless of the participant retention methods used, participants may voluntarily withdraw from the 
study for any reason at any time. The Site Investigator of Record or designee also may withdraw 
participants from the study to protect their safety and/or if they are unwilling or unable to comply with 
required study procedures. Participants also may be withdrawn if the study sponsor, government or 
regulatory authorities, or site IRBs/ECs terminates the study overall or at a specific site prior to 18 weeks.  
 
Every reasonable effort will be made to complete final evaluations for participants who terminate from 
the study prior to the last study assessment or visit; study staff will record the reason(s) for all withdrawals 
from the study in participants’ study records. 
3.8 
Replacement of Study Participants 
Data from participants who permanently discontinue study treatment will be used in analyses. Study 
participants who miss two consecutive scheduled doses, miss any pharmacokinetic samples, or 
permanently discontinue DOT PrEP will be replaced so that approximately 54 evaluable participants 
complete the study. No more than 20% of the target population (n=54) will be replaced. Data from 
subjects who discontinue prematurely will be used in analyses. Cisgender women who become pregnant 
will be replaced but will continue to be followed up to the end of their scheduled protocol study follow up. 
Seroconversions (unlikely, though possible) will not be replaced. 
4 
STUDY PRODUCT 
The study product is Descovy® formulated as tenofovir alafenamide (TAF) 25 mg/ emtricitabine 200 mg 
(FTC). 
4.1 
Study Product Formulation  
Each TAF-FTC tablet contains a co-formulation of TAF 25mg / FTC 200mg. An authorized study clinician 
will prescribe TAF-FTC as part of this study, with dosing instructions as described in this protocol. 

 
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4.1.1 Study product storage  
Prior to dispensing, TAF-FTC tablets will be stored in the pharmacy in the original container. Each bottle 
contains a desiccant to protect the product from humidity. Study drug is to be stored at 68 °F to 77 °F (20 
°C to 25 °C), with temperature excursions permitted between 15° to 30°C. 
4.2 
Source of Study Product and Accountability 
Gilead Sciences will donate the study drug for this study. Study drug will be shipped to the investigational 
pharmacy and dispensed through the Thika Research Site pharmacy according to the research pharmacy 
policies and procedures of Kenya Pharmacy and poison board. The pharmacist of record will receive and 
inventory study medication, will dispense and track prescriptions, and will provide directions for returning 
unused medications for destruction according to local policy. The pharmacist of record will track the 
accountability of the study medications according to established procedures developed by the 
investigational pharmacy.  
4.2.1 Study product dispensation 
Two supplies of study drug will be dispensed for each participant. Both supplies will be dispensed in the 
original containers. Study personnel will be in possession of the main medication supply, which will be 
stored in a locked cabinet except during transportation to and from the directly observed dosing visits. 
This main supply will be enough for the entire 10-week DOT dosing period (enough medication to cover 
10 weeks will be dispensed for the 70-84 day dosing window). Study personnel will record on the bottle 
the date that it is opened, and will ensure that opened bottles are used within 8 weeks. The locked cabinet 
will be in a temperature-controlled building, which is maintained at approximately 21°C. A second 
medication supply, a take-home supply, will be given to participants for non in-person dosing (video-
streaming). Participants will be reminded to keep the medication in the original container with the 
desiccant, and to store it in a dry place with the cap tightly sealed. This take-home supply will be a 
maximum of one bottle of medication, with additional bottles given to participants when the current bottle 
is exhausted. 
4.2.2 Return and Destruction of Study Product 
Unused medications will be returned to the site study pharmacy at the end of the dosing periods or after 
a participant permanently discontinues study drug. The site pharmacy will account for and manage the 
returned medications in accordance with the local policies and procedures.  
4.3 
Assessment of Participant Adherence with Study Product/Intervention 
Adherence will be assessed with directly observed dosing. All doses will be observed in person, when 
possible, at an agreed-upon private room at the research clinic or other predetermined location to 
maximize convenience for the participant. In circumstances where doses cannot be witnessed in person, 
doses will be witnessed by live audio-video communication or time-stamped videos . If video confirmation 
fails, this will be recorded as non-DOT dose. 
4.4 
Concomitant Medications  
Concomitant medications will be evaluated on a case-by-case basis for interactions with the study 
medications. Certain medications are permitted, and other medications are prohibited as described in the 
sections that follow. Medications not listed in these sections will be evaluated for potential interactions 
with the study medications or procedures and a decision to enroll the subject will be made accordingly. 
Additionally, should a new concomitant medication be started during the study, the same evaluation will 
take place.  
4.5 
Prohibited Medications  
Prohibited 
concomitant 
medications 
are: 
investigational 
agents, 
aminoglycosides, 
ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir, cyclosporine, amphotericin B, 
foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications 

 
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including TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing 
lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively.  
4.6 
Precautionary Medications  
Any medication or herbal supplement not listed under sections prohibited medication section will be 
evaluated on a case-by-case basis for interactions with the study medications. Should there be potential 
for serious interaction, based on the opinion of the investigators, the subject will not be invited to 
participate. Additionally, should a new concomitant medication be started during the study, the same 
evaluation will take place.  
4.7 
Toxicity Management 
Safety related laboratory testing will be performed at study entry and at week 8 and or as indicated by 
clinician during follow up. If enrollment occurs more 30 days after screening, entry safety labs will be 
repeated. These include HIV rapid testing, complete blood count, HBV surface antigen, serum creatinine, 
and urine pregnancy test. Toxicity will be managed in consultation with a clinician on the protocol. The 
clinician may discontinue the study drug at any time if he/she feels that continued use would be harmful 
to the participant. The PSRT should be consulted when possible. The PSRT will be consulted when 
considering further holding or recommencing study medication.  
4.8 
HIV Seroconversion 
Frequent testing for HIV acquisition during the study period will allow prompt cessation of study drug in 
an HIV-infected participant, minimizing the risk that resistant virus will emerge. Therefore, HIV testing will 
be performed at all monthly study visits. HIV rapid testing and specimen collection will be completed prior 
to administration of study medication. Participants who have any reactive or positive HIV test result after 
initiating PrEP will be instructed to discontinue study drug immediately and will have further testing to 
clarify their HIV infection status, as described in Section 5.3. Any enrolled participant who is confirmed to 
have acquired HIV infection during the study will permanently discontinue study product and will be 
transitioned to a local HIV care clinic for appropriate follow-up and clinical management. Procedures for 
participants who acquire HIV infection are described in Section 5.3.  
4.9 
Dose Modification 
Study personnel will record all events of participants who vomit immediately after dosing. Participants will 
not be asked to re-dose, unless they are confident that a recurrence of vomiting can be avoided. 
Additionally, re-dosing will only be allowed if an intact tablet is visible in the emesis. The same directly 
observed dosing rules will apply if re-dosing is attempted. Dose modifications of up to 3 sequential missed 
doses will be allowed if a participant has, for example, an acute gastrointestinal illness. Further dose 
modifications or other dose modification issues will be discussed with the PSRT. The PSRT may decide 
on further missed doses, or participant withdrawal from the study.  
5 
STUDY PROCEDURES 
An overview of the study visits and procedures schedule is presented in Table 5. Presented below is 
additional information on visit-specific study procedures.  
5.1 
Screening Procedures 
Screening for COVID-19 symptoms and protection measures: We will follow the standard of care of 
the Kenya Ministry of Health, KEMRI, and WHO guidelines on the COVID-19 virus.  Participants will be 
informed about practicing good hand hygiene, masking, good respiratory hygiene, and maintaining social 
distancing. Staff will adhere to social procedures including maintaining a six foot distance and  wearing 
masks. Unvaccinated participants and staff will be screened for COVID-19-related symptoms when they 
arrive at the clinic using a checklist to check for risk of COVID-19 exposure based on symptoms or 
contacts. Any person that comes to the clinic with symptoms consistent with COVID-19 that include 1 or 
more of fever, cough (dry or productive), dyspnea, or myalgias will be isolated. Participants will be 
educated about the Ministry of Health specified measures for seeking healthcare during this time. Referral 

 
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mechanisms to local public health facilities are in place. Finally, the clinical site will maintain a register of 
all visitors and participants who enter the study site, to support usual care contact tracing efforts where 
necessary. 
 
At the screening visit a qualified study clinician will perform a history and physical exam for each 
participant. A complete medication history will be obtained including all drug allergies, immunization 
history, prescription, over the counter, and herbal treatments. Vital signs will include height, weight, blood 
pressure, pulse, respiratory rate and temperature. The following procedures will be conducted: 
• 
Informed consent 
• 
Safety Labs: Complete blood count (CBC, specifically hematocrit and hemoglobin), HBV 
surface antigen, serum creatinine)  
• 
HIV antibody (rapid test or blood) 
• 
Urine pregnancy test 
• 
Medical, medication, vaccine history  
• 
Physical exam 
A screening test(s) may be repeated within the 30-day screening window. A participant who is unable to 
schedule a study entry visit within the 30-day screening window must be re-screened prior to entry into 
the study. Participants who have not been immunized for HBV will be offered vaccination, as per standard 
of care. An HBV Antibody test may be ordered for participants who are unsure of their vaccination history.  
5.2 
Enrollment and Follow up Procedures  
Up to 54 evaluable HIV uninfected participants will be enrolled and followed up for 18 weeks: 10 weeks 
with DOT PrEP and up to 8 weeks for post drug kinetics sampling, with one visit at one week following 
dose cessation and an additional visit to occur between weeks 12 to 18. Enrollment must occur within 30 
days of screening. An eligible participant who is unable to schedule a study entry visit within the 30-day 
screening window must be re-screened prior to entry into the study. All enrolments will be scheduled on 
specific days to avoid confusion in implementing the proposed dosing and sampling scheme. An adverse 
event questionnaire and medical and medication review will be conducted at each visit from study entry 
(enrollment) through week 10. Safety labs and vitals can be ordered as needed at any visit. 
5.2.1 Dosing schedule and assessment of compliance 
The design of the study is guided by the ~17-day half-life of TFV-DP in DBS, and includes 10 weeks of 
dosing to achieve approximately 90% of steady-state, weekly sampling at convenience times (i.e., rather 
than troughs), and three dosing groups (2, 4, and 7 doses per week) to demonstrate dose-proportionality. 
All cisgender women will have 10 weeks of DOT PrEP to establish steady state in DBS and WB. We 
have chosen a dosing frequency scheme for non-daily doses to directly replicate the STRAND DOT study 
schedule based on the ~17-day half-life of TFV-DP in DBS: The 2 doses per week will be taken on 
Monday and Tuesday, and the 4 doses per week on Monday, Tuesday, Thursday, and Friday. This 
schedule will permit simultaneous evaluation of concentrations derived from intermittent and day-by-day 
dosing. The operationalization of specific days for dose taking can be adjusted prior to study start while 
maintaining the randomized adherence patterns (frequency of dosing taking) to permit efficient study 
operations and to minimize the burden on study participants. This is possible due to the long half-life of 
TFV-DP and planned sampling at steady state. Therefore, any chosen days would be appropriate. 
All doses will be witnessed, as described above, in person by a study personnel in either a private room 
at the Thika clinic or at another predetermined location to maximize convenience for the participant. On 
dosing visits, the participant will take the dose by mouth and study personnel will ensure the tablet is 
swallowed by asking the participant to show that their mouth is empty. Flexible clinic scheduling will be 
available to promote high rates of follow-up and compliance and to minimize participants’ burden. Where 
dosing cannot be witnessed in person, dosing will be witnessed over video via WhatsApp, Zoom, 
FaceTime, Skype, or other video-streaming device that is agreed upon by the participant and study 

 
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personnel. Only cisgender women with an active smart phone will be enrolled in this pharmacokinetics 
study to permit offsite observation of dose taking for the required DOT PrEP, and participants will be 
supported with commensurate data/internet bundles. A one-month supply of back-up medication will be 
provided to participants at study enrollment to be used if the participant is unable to attend their visit at 
the clinic. All doses taken offsite will be directly observed by study staff by live video streaming and 
participants will be asked to open their mouth afterwards to confirm swallowing. Dosing may occur at 
variable times within the assigned dosing day. All doses will be taken without regard to food, but meal 
information will be collected with each dosing event. 
Study personnel will use a dosing log to document directly observed doses. Participants will be given a 
detailed calendar that shows scheduled dosing days. This schedule will also be reinforced when study 
personnel interact with participants.  
5.2.2 Protocol pharmacology sampling visit schedule 
During protocol-specified clinic visits (described below and in Table 2), a blood sample will be collected 
from an arm vein for plasma/WB/RBC/DBS/PBMC isolation and safety laboratories. Hair will be cut from 
the scalp for comparison with other drug measures. Adverse events will be assessed. All protocol-
specified clinic visits are detailed below. Each protocol-specified clinic visit will have a window of up to 
10 days for sample collection. 
Clinic visit 1: Study entry visit (must be within 30 days after screening visit) 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
Study blood work: WB, DBS, PBMC, plasma, (pre-drug for endogenous molecules 
such as nucleosides)  
• 
Urine pregnancy test (urine β HCG) 
• 
Study urine: (baseline endogenous molecules such as nucleosides) 
• 
STI tests (CT, GC, syphilis, HSV-2) 
• 
Blood work: hDNA for those who consent to drug transport gene testing 
• 
Vaginal swab 
• 
Dispense back up PrEP medication: subject home supply 
• 
Dispense study dosing calendar 
• 
DOT: Witness first PrEP dose 
 
Clinic visit 2:  Week 1 Day/Dose 4 visit (for 2 doses per week group this will be 4 days since first 
dose:  
• 
Study Bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine  
• 
Finger stick for DBS 
• 
Cervicovaginal biopsy: Random subset (50%) of cohort. These participants 
will not have a biopsy collected at the Week 1, Day 7 visit. 
• 
Vaginal swab 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 3:  Week 1 (Dose 7) visit:  
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine  
• 
Finger stick for DBS 

 
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• 
Vaginal biopsy: Random subset (50%) of cohort, comprising participants who 
did not have a biopsy collected at the Week 1, Day 4 visit 
• 
Vaginal swab 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 4:  Week 2 (Dose 14) visit: 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine  
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 5:  Week 3 (Dose 21) visit: 
• 
Study bloodwork: WB, DBS, plasma 
• 
Study urine 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 6:  Week 4 (Dose 28) visit:  
• 
HIV rapid test  
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine 
• 
Finger stick for DBS 
• 
Vaginal biopsy (all participants) 
• 
Vaginal swab 
• 
Hair collection 
• 
Urine pregnancy test (urine β HCG) 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 7:  Week 5 (Dose 35) visit: 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine  
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 8:  Week 6 (Dose 42) visit: 
• 
Study bloodwork: WB, DBS, PBMC, plasma 

 
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• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
• 
Study urine 
 
Clinic visit 9:  Week 7 (Dose 49) visit: 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine  
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 10:  Week 8 (Dose 56) visit:  
• 
HIV rapid test 
• 
Urine pregnancy test (urine βHCG) 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Finger stick for DBS 
• 
Study urine 
• 
Vaginal biopsy (all participants) 
• 
Vaginal swab 
• 
Hair collection 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 11:  Week 9 (Dose 63) visit: 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 
 
Clinic visit 12:  Week 10  Dose 70) visit:  
• 
HIV rapid test 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Finger stick for DBS 
• 
Study urine 
• 
Safety Labs: Creatinine 
• 
STI testing 
• 
Medical, sexual, contraception, antenatal and vaccine history review 
• 
AE assessment 
• 
Concomitant Medication Review 
• 
DOT 

 
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Clinic visit 13: Post DOT PrEP visits (one week following dose cessation): One visit at least 48 
hours after the last DOT PrEP dose. 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine 
 
Clinic visit 14: Post DOT PrEP visits (Week 12-18): One visit at least 14 days after visit above (i.e., 
the visit can occur any time between 2-8 weeks after the last DOT F/TAF PrEP which is between about 
week 12 and week 18 since enrollment) 
• 
Study bloodwork: WB, DBS, PBMC, plasma 
• 
Study urine 
• 
Hair collection 
 
5.2.3 Clinical Evaluations/Procedures 
Scheduled protocol visits and procedures are outlined in Table 5. At the screening visit a qualified study 
clinician will perform a history and physical for each participant. A complete medication history will be 
obtained including all drug allergies, immunization history, prescription, over the counter, herbal 
treatments, contraception use history. Vital signs will include height, weight, blood pressure, pulse, 
respiratory rate and temperature. 
5.2.3.1 
Specimen collection 
All pharmacokinetic samples must be collected as per the protocol-specified schedule. Each protocol-
specified pharmacokinetic sampling visit will have a window of up to 10 days for sample collection. The 
pharmacokinetic samples will be collected as follows: 
Blood 
A blood sample will be obtained at protocol specified visits to process plasma, whole blood, DBS, and 
PBMCs. On a given study day blood collection, up to 21mL of blood for study bloodwork will be drawn 
with no planned timing relationship with dosing. The blood will be collected from an arm vein by trained 
clinic staff according to study site policies and procedures.  

 
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The schedule of protocol visits and procedures are outlined in Table 2. 
 [x] Indicated if screening occurred more 30 days before planned enrollment. The screen and entry visits must be ≤ 30 days apart.  
a. Safety labs or vitals can be performed as needed at any time 
b. DOT performed if applicable per randomization schedule 
c. Protocol-specified safety labs include: CBC, HBAg, Creatinine clearance, in addition to monthly HIV testing and urine pregnancy tests. 
d. Study Bloodwork: WB, DBS, PBMC, plasma and all available blood cell types; Study Urine: endogenous molecules such as nucleosides.  
*PBMC is collected bi-weekly (baseline, week 2, 4, 6, 8, 10) 
e. Study medications will be dispensed as described  
f. Random subset (50%) on day 4 and the remaining subset (50%) on day 7. All participants will have week 4 and week 8 sample. 
Vaginal swab and tissue 
Vaginal swabs and a vaginal tissue sample will be collected. Vaginal biopsies will be taken with 2.3 x 4.2-
mm Tischler gold-plated gynecological forceps.  
Justification for vaginal tissue sampling: Vaginal mucosa is a tissue of great relevance to the acquisition 
of HIV infection for cisgender women. The planned sampling schedule will help to define early drug 
kinetics and how soon drugs accumulate in vaginal tissue following PrEP initiation the week until steady 
state is reached. To minimize risk associated with this procedure and the burden on study participants, 
we will ensure each participant will have only one biopsy in a 4 week-period by sampling separate 
participants at days 4 and 7 of Week 1. Thus, in week 1, half of the participants will be biopsied on day 
4, and half will be biopsied on day 7. All participants will provide tissue samples at week 4 and 8. 
Table 2: Schedule of protocol visit schedule and procedures. 
 
Screening Entry 
DOT PrEP Period (weeks) 
 
Post DOT Period 
 
Timeline (weeks) 
 
 
W1 
W2 
W3 
W4 W5 W6 
W7 
W8 W9 
W10 
W11 
W12-18 
Day 4 Day 7  
 
 
Clinic Visits # 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
13 
14 
Procedure 
11 
12 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical, sexual, contraception, 
antenatal history review, vaccine history 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Physical exam a 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense back up PrEP medicatione 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Issue medical calendar 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE assessment 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Safety Labs a,c 
x 
[x] 
 
 
 
 
 
 
 
 
x 
 
 
 
 
Urine βHCG a 
x 
[x] 
 
 
 
 
x 
 
 
 
x 
 
 
 
 
HBS Ag 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 rapid test a 
x 
[x] 
 
 
 
 
x 
 
 
 
x 
 
 
 
 
Hair collection 
 
 
 
 
 
 
x 
 
 
 
x 
 
 
 
x 
hDNA  
 
x 
 
x 
 
 
 
 
 
 
 
 
 
 
 
Study Bloodwork d (WB, plasma, DBS, 
PBMC)*PBMC is collected bi-weekly 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
Vaginal tissuef 
 
 
x 
x 
 
 
x 
 
 
 
x 
 
 
 
 
Vaginal swab 
 
x 
x 
x 
 
 
x 
 
 
 
x 
 
 
 
 
DBS by fingerstick 
 
 
x 
x 
 
 
x 
 
 
 
x 
 
 
 
 
Study Urine d 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
Concomitant Medication Review 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
STI testing (CT,GC, syphilis, HSV-2) 
 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
DOTb 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 

 
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Urine testing 
A urine samples will be obtained at each visit for future testing to help refine models of prediction of PrEP 
adherence in cisgender women based on urine. The participant will be asked to void a small amount of 
urine into a sterile specimen container per standard procedures.  
Hair collection 
A small amount of hair (about 50-100 strands) will be collected from the occipital portion of the scalp in 
order to refine models for prediction of long-term PrEP adherence in cisgender women based on hair.  
The hair will be cut from as close to the scalp as possible with scissors. The hair that is cut will be taken 
from underneath the top layer of hair to minimize visibility of the removed hair. Measuring TFV/FTC 
exposure in small hair samples is feasible and acceptable in Kenya PrEP trials36. 
Blood for DNA 
Blood for DNA will be obtained during Week 1 visit from participants who consent to sample storage for 
future testing. Genomic DNA will be isolated using a commercially available kit, according to standard 
manufacturer protocol. The DNA will be analyzed pharmacogenetic studies of protein drug transporters, 
and will not be used for whole genome sequencing. Only gene DNA analysis related to antiretroviral drug 
disposition or treatment response (drug transporters) will be evaluated. An addendum consent will be 
used to obtain informed consent for future testing.  
5.3 
Procedures for participants identified as HIV infected and/or pregnant 
While it is expected to be very rare, this study may identify persons who become infected with HIV-1 
during follow-up. Study staff will provide participants with their HIV test results in the context of post-test 
counseling. In the case of a positive test, a blood sample will be obtained for HIV drug resistance testing 
conducted through the standard national GEMS protocol for drug resistance surveillance. These results 
will be communicated to participants as soon as they are available. Persons identified as HIV infected 
during the study will be initiated on free HIV treatment and will also be referred to nearby HIV care 
services for follow up at completion of this trial. For participants who are pregnant and become infected 
with HIV during study follow-up, every effort will be made to facilitate immediate access to programs for 
preventing mother-to-child HIV transmission for appropriate antiretroviral treatment to reduce the 
probability of HIV transmission from mother to child.  
6 
SAFETY MONITORING AND ADVERSE EVENT REPORTING 
6.1 
Safety Monitoring 
A Protocol Safety Review Team (PSRT) discuss and regularly monitor safety issues that arise during the 
study, as outlined in this section. The PSRT will consist of the Principal Investigators, a study coordinator, 
a Gilead representative, and a Study Safety medical Officer. Email communications or calls will be held 
approximately every month, or as needed to discuss safety or study-related concerns, as described 
below. Conference calls will be held approximately every 6 months to summarize cumulative safety 
reports and enrollment. These reports will include all clinical and laboratory adverse events; social harms; 
enrollment including gender/ethnicity; and disqualified/excluded individuals. The Seattle-based Study 
safety monitor will review all safety data, and will prepare routine study conduct and safety reports for the 
PSRT, which will meet by conference call approximately every 6 months or as needed. The study site 
Investigators are responsible for continuous close monitoring and management of AEs in conjunction 
with IoRs. Sites are required to have detailed SOPs describing methods for AE reporting and toxicity 
management to ensure that AEs are reported and managed in accordance with the protocol and for 
alerting the PSRT if unexpected concerns arise 

 
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6.2 
Clinical Data Review 
A multi-tiered safety review process will be followed for the duration of this study. The study site 
investigators are responsible for the initial evaluation and reporting of safety information at the participant 
level, and for alerting the PSRT if unexpected concerns arise.  
Participant safety data will also be monitored by the Seattle-based Study safety monitor, who will review 
incoming safety data for completeness and consistency on an ongoing basis. Events identified as 
questionable, inconsistent, or unexplained will be queried for verification.  
The Seattle-based Study safety monitor will prepare routine study conduct and safety reports for the 
PSRT, which will meet by conference call approximately every 6 months and will review accrual and 
retention data, as well as safety data. More frequent or ad hoc reviews of safety data may be conducted 
by the PSRT as needed. A recommendation to stop the trial may be made by the PSRT at any such time 
that the team agrees an unacceptable type and/or frequency of AEs has been observed. If at any time a 
decision is made to discontinue the study product in all participants, the protocol chair will notify 
appropriate regulatory agencies, as well as the site IoRs, who will notify the responsible IRBs 
expeditiously 
6.3 
Adverse Event Definition and Reporting 
An adverse event (AE) is defined as any untoward medical occurrence in a clinical research participant 
administered an investigational product and which does not necessarily have a causal relationship with 
the study product (TAF/FTC). As such, an AE can be an unfavorable or unintended sign (including an 
abnormal laboratory finding, for example), symptom or disease temporally associated with the use of an 
investigational product, whether or not considered related to the product. 
Study participants will be provided a 24-hour telephone number and contact information and instructed 
to contact the study clinician to report any AEs they may experience. For life-threatening events, they will 
also be instructed to seek immediate emergency care. Where feasible and medically appropriate, 
participants will be encouraged to seek evaluation where the study clinician is based, and to request that 
the clinician be contacted upon their arrival. With appropriate permission of the participant, whenever 
possible, records from all non-study medical providers related to AEs will be obtained and required data 
elements will be recorded on study CRFs. All participants reporting an AE will be followed clinically, until 
the AE resolves (i.e., returns to baseline) or stabilizes.  
Study site staff will document AEs in source documents and the appropriate e-CRF. Grade 1 and higher 
clinical AEs, Grade 2 and higher laboratory AEs, and any AE (clinical or laboratory) that leads to a study 
product hold (temporary or permanent) that are reported by or observed in enrolled (defined as after 
randomization has occurred) study participants will be captured on AE e-CRFs regardless of their severity 
and presumed relationship to the study product. AE severity will be graded per the DAIDS Table for 
Grading Adult and Pediatric Adverse Events, Version 2.1 corrected, July 2017.  
6.4 
Relationship to Study Product 
Relatedness is an assessment made by a study clinician of whether or not an adverse event is related to 
the study product. The relationship of all AEs to the study product will be assessed per the clinical 
judgment of the investigator based on the package insert and investigator’s brochure.  
6.5 
Grading Severity of Events 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected 
Version 2.1, July 2017, will be used for determining and reporting the severity of adverse events. The 
DAIDS grading table is available on the DAIDS RSC website at https://rsc.niaid.nih.gov/clinical-research-
sites/daids-adverse-event-grading-tables. 

 
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6.6 
Serious Adverse Event (SAE) 
All SAEs as defined by ICH guidelines will be reported regardless of relationship to the study agent(s), 
and are as follows: 
– Results in death, 
– Is life-threatening, 
– Requires inpatient hospitalization or prolongation of existing hospitalization, 
– Results in persistent or significant disability/incapacity, or 
– Is a congenital anomaly/birth defect 
– Important medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the patient or may require intervention to prevent one of the 
outcomes listed in the definition above. Such determination may be made through medical or 
scientific judgment. Examples include the following: intensive treatment in an emergency room or 
at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; development of drug dependency or drug abuse; etc. 
6.7 
Discontinuation of Study Medication 
Subjects may withdraw from the study at any time. Any participant who prematurely discontinues study 
medication (for toxicity or pregnancy) should be followed for study duration. Subjects who become 
pregnant or who acquire HIV infection will have study drug discontinued but will be followed to determine 
the pregnancy outcome.  
6.8 
Discontinuation of study drug with toxicity 
Grade I or II toxicity will be managed in consultation with a clinician on the protocol. The clinician may 
add follow up testing and evaluations, as medically indicated.  Study drug can be continued except as 
noted below. 
Grade III toxicities will be communicated to the PSRT and managed under the direction of a study 
physician. Follow up testing and evaluations will be added, as medically indicated. The toxicity will be 
evaluated for subject safety. If the adverse event may put the subject at increased risk, or jeopardizes 
the study’s intent, even if not related with study drug, the subject will discontinue study drug. The PSRT 
will decide whether study drug can be restarted. If the adverse event is deemed not to be a significant 
health risk, the PSRT may recommend continuing study drug with close monitoring.  
Grade IV toxicities will be communicated to the PSRT and managed under the direction of a study 
physician. If a grade IV event is related to the study drug, the participant will permanently discontinue the 
study drug and will be followed as medically indicated. If the grade IV is not related to the study drug, the 
PSRT will recommend whether study drug can be continued with close monitoring, or 
permanently/temporarily discontinued.    
Participants who discontinue drug permanently due to a study drug-related AE will be followed until AE 
resolves or stabilizes and then the subject will be discontinued from the study.  
6.8.1 AE Grades 1 or 2 
Grade I or II toxicity will be managed in consultation with a clinician on the protocol. The clinician may 
add follow up testing and evaluations, as medically indicated.  Study drug can be continued except as 
noted below.  
6.8.2 AE Grade 3 
TAF-FTC may be continued as directed by the site investigator if a Grade 3 toxicity is considered to be 
unrelated to the study medication. Study medication will be temporarily withheld if Grade 3 toxicity is 
considered to be related to the study medication. After a Grade 3 toxicity returns to Grade 1, the 
participant can be reintroduced to medication after consultation with the site investigator and other 
members of the PSRT. If a Grade 3 toxicity recurs and is considered to be related to study medication, 
TAF-FTC will be permanently discontinued. 

 
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6.8.3 Grade 4 
For all Grade 4 laboratory-identified or clinical toxicities, TAF-FTC will be withheld unless it is determined 
to be not related. If a Grade 4 laboratory toxicity is not confirmed by repeat testing, it should be managed 
per algorithm for the new toxicity grade. Participants with Grade 4 AEs will be followed until the event 
resolves to baseline or stabilizes. Study drug may be restarted in the event of the resolution of a Grade 
4 AE back to Grade 1, after consultation with the site investigator and other members of the PSRT. If the 
toxicity recurs to Grade 3 or higher after TAF-FTC is restarted and is considered to be related to TAF-
FTC, the study medication will be permanently discontinued. 
6.8.4 Creatinine Clearance 
Participants who enroll with a Grade 2 CrCl will discontinue study drug only if there is an increase in 
severity (to Grade 3 or 4). If the calculated creatinine clearance is <60mL/min, it should be confirmed 
ideally within approximately one week of the receipt of the results. Study drug should be halted 
temporarily awaiting confirmatory testing. The PSRT should be consulted for further guidance about 
restarting study drug for participants who fail to have a confirmed test within two weeks of receiving the 
initial result.If the calculated creatinine clearance is confirmed to be <60 mL/min, the study drug must be 
temporarily discontinued. The participant will be monitored as deemed clinically necessary in consultation 
with the PSRT until level returns to baseline (screening value) or stabilizes. 
6.9 
Reporting Requirements for this Study 
For each study participant, the SAE/EAE reporting period begins at Enrollment (Day 0) and ends when 
the participant’s follow-up in the study ends. All reportable SAEs occurring during the study reporting 
period will be reported to the principal investigator  
6.10 Social Impact Reporting 
It is possible that participants' involvement in the study could become known to others, and that a social 
impact may result (i.e., because participants could be perceived as being HIV-infected or at risk or "high 
risk" for HIV infection). For example, participants could be treated unfairly, or could have problems being 
accepted by their families and/or communities. A social impact that is reported by the participant and 
judged by the IoR/designee to be serious or unexpected will be reported to the responsible site’s IRBs at 
least annually, or according to their individual requirements. Social impacts will be collected and reported 
on CRFs during regular visits. In the event that a participant reports a social impact, every effort will be 
made by study staff to provide appropriate care and counseling to the participant as necessary, and/or 
referral to appropriate resources for the safety of the participant. The study site will provide such care 
and counseling in accordance with standardized guidance in the SSP Manual. While maintaining 
participant confidentiality, study site may engage their CAB in exploring the social context surrounding 
instances of social impacts, to minimize the potential occurrence of such an impact. 
7 
STATISTICAL CONSIDERATIONS 
7.1 
Review of Study Design 
An open-label, randomized, three-arm, directly observed therapy, pharmacokinetic study. HIV-uninfected 
non-pregnant cisgender women will be randomly assigned 1:1:1 to 1 of 3 dosing frequencies of DOT 
TAF-FTC: 2, 4, or 7 doses/week to help differentiate poor and modest from perfect adherence. Drug 
concentrations in blood, cervico-vaginal fluid, and tissue will be measured during the study. 
7.2 
Study endpoints 
• 
Aim 1: Mean, variance, and dose proportionality for TFV-DP or TFV in plasma, DBS, and PBMC 
for 2, 4, 7of DOT TAF-FTC dosing per week.  
• 
Aim 2: Prediction model of adherence rate by level of TFV-DP in DBS. 

 
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7.3 
Data Analysis 
7.3.1 Primary outcomes 
Primary outcome 1: The goal is to describe the frequency of adverse events, including emergent HIV 
infection during the study period. We will conduct a descriptive analysis for meeting PrEP157 eligibility 
among participants. The distribution of demographics and graded adverse events will characteristics by 
overall and study arms and proportions will compared between study arms using chi-square statistics. 
Primary outcome 2: The goal is to quantify the effect of dose on steady state TFV-DP in DBS and PBMC 
based on an incomplete block design. Css (drug concentration at steady state) will likely require a 
normalizing log transform, such that geometric means and CIs will be reported.  Dose proportionality will 
be assessed using the power model (on the natural log scale)   ln(Yijk) = µ  + Si + Pj + blog(Dk) + eijk  (Eqn. 
1).37  Where Yijk is the response, Css, for the kth dose (k=2, 4, 7 doses/week), jth period (j=1,2), ith 
subject(i=1,…45); µ is the overall mean, Si is a random subject effect, Pj is the period effect and eijk is 
random error.  Dose proportionality dictates that b=1 for dose-dependent parameters and we will assume 
dose proportionality if the 90% CI is contained within the limits (0.8, 1.25).  The SAS mixed procedure 
will be utilized for model (Eqn 1), again assuming a random subject effect.  Although we do not anticipate 
a period effect, our design allows us to test this effect.  For the primary analysis, we assume no effect of 
‘non-daily dosing’ regimens; although this will be examined in a secondary analysis. If dose 
proportionality is not shown, we will examine proportionality separately for each of the ‘‘non-daily dosing’ 
dosing regimens. If dose proportionality is still not demonstrated when adherence regimens are examined 
separately we will consider dose as a categorical predictor. 
In addition to the power model, we will utilize nonlinear mixed effects models using PK software 
(NONMEN and/or ADAPT-5) to model drug concentration over time on drug.38-42  For this analysis, all 
available drug concentration samples will be utilized, thereby accounting for missed doses due to protocol 
deviations. Change in objective function and/or AIC will be used to compare models. This approach will 
be used to further probe dose proportionality and the final model(s) will be used as a basis for simulation 
studies.  
Primary outcome 3: The goal is to identify TFV-DP cut points associated with adherence levels. For the 
primary analyses, we will attempt to discriminate adherence for 2, 4 and 7 dosing based upon TFV-DP. 
As above, we will combine the “non-daily dosing’” regimens. Linear mixed models with random intercepts, 
25th percentiles, and receiver operating characteristics curves will be used to generate predicted 
concentration thresholds for varying dosing frequency (ranging from 1 to 7 doses/week) for each matrix-
analyte pair. Analyses will be adjusted for age, contraception use, study arm, BMI, eGFR, and hematocrit. 
7.3.2 Secondary outcomes 
1. Examine models to predict non-daily adherence based on TFV/FTC and FTC-TP/TFV-DP in DBS. 
We assume the modeling approaches of Aim-1. We will first consider a saturated model allowing 
a separate mean for each dose/adherence group. The results will then be compared to a reduced 
model with a class variable indicating non-daily dosing groups” or 100% dosing (that is, the effect 
of “non-daily dosing” adherence does not differ by dose groups). Drug concentration predictors of 
“non-daily dosing” will focus on TFV-DP in relationship to other drug moieties such as FTC-TP 
and FTC and TFV. For instance, the ratio of TFV-DP to FTC-TP may be used as a predictor of 
“2” versus “4 dosing per week. A proportional odds logistic approach which allows for an ordinal 
outcome and extensions which control for correlations between repeated measurements on a 
subject will be utilized in SAS or R statistical software.  In addition, we will employ PK models 
(see Aim-1) to simulate TFV-DP to FTC-TP ratios for other dose regimens and estimate cut points 
for predicting non-daily dosing patterns. 
2. Examine relationships among drug concentrations in plasma, RBC, DBS, and PBMC. 

 
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We will use mixed and non-linear mixed effects models to determine if concentrations in various 
matrices are related.  
3. Evaluate the influence of demographics, biological on drug concentrations. 
Kruskal-Wallis parametric test will be used to compare demographics and key study variables 
(e.g., age, pregnancy, HCT, contraception use, study arm, BMI, eGFR). Non-linear mixed effects 
models also will be used to probe covariate effects on PK. Secondary analyses are considered 
hypothesis generating and will not correct for multiple comparisons. 
4. Compare drug concentrations in DBS from fingerstick versus transferring blood from blood tubes. 
Since these are paired DBS samples, we will compute the ratio of TFV-DP in the two samples 
and a mixed model on the natural log of the ratio will be utilized to determine if CI is within 0.8 
and 1.25, indicating equivalence. Bland-Altman analyses will also be evaluated. 
7.4 
Sample Size Considerations 
The overall sample size was chosen to have up to 18 cisgender women in each relevant group (overall, 
n=54 non-pregnant cisgender women) sufficient to provide precise information on drug concentrations 
and to balance feasibility, efficiency, and provide robust TAF/FTC data in DBS for cisgender women. The 
sample size for drug concentration parameters is based on ensuring precision in the estimates to 
accurately describe the concentration kinetics of TAF/FTC in non-pregnant cisgender women and is 
consistent with multiple DOT PrEP studies done in US populations43, 44. The precision desired is a mean 
TFV-DP in DBS at steady state within ±15% of the true population mean. The mean (± standard deviation) 
TFV-DP at steady-state in HIV-uninfected US cisgender men and cisgender women following directly 
observed doses of 25 mg TAF/200mg FTC once daily for 12 weeks was 2381 ± 601 fmol/punches 
[coefficient of variation (CV) of 25%] (Anderson et al)43. Based on this variability and assuming average 
TFV-DP results are normally distributed, to be 90% confident that the DBS TFV-DP sample mean is 
within 15% of the true mean, a sample size of 15 participants is required for non-pregnant cisgender 
women with conservative assumptions. With the planned enrollment of 18 cisgender women per group 
for this study, even a 10% non-completion rate at 8 weeks of DOT therapy, we provide ample data to 
estimate steady-state means to within 10% in cisgender women.  
7.5 
Randomization and Blinding Procedures 
The study design will be an open-label, randomized study with three arms. The randomization 
assignment will be made at enrollment if the participant is eligible and agrees to enroll. Randomization 
will be according to the PrEP dosing frequency and vaginal tissue collection plan (either sampling day 4 
or day 7) 1:1:1 fashion programmed by the study statistician and generated from REDcap.  
The allocation of participants for the 3 study arms will be the following: 
 
2 doses per week 
4 doses per week 
7 doses per week 
Total 
Total 
18 
18 
18 
54 
8 
HUMAN SUBJECTS CONSIDERATIONS 
8.1 
Ethical Review 
The protocol, site-specific informed consent form, participant education and recruitment materials, and 
other requested documents — and any subsequent modifications — will be reviewed and approved by 
the University of Washington Human Subjects Ethical Committee and the Scientific and Ethics Review 
(SERU) Committee of the Kenya Medical Research Institute responsible for oversight of research 
conducted at the study site. 

 
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Subsequent to initial review and approval, the responsible IRBs/ECs will review the protocol at least 
annually. The Investigator will make safety and progress reports to the IRBs/ECs at least annually, and 
within three months of study termination or completion. These reports will include the total number of 
participants enrolled in the study, the number of participants who completed the study, all changes in the 
research activity, and all unanticipated problems involving risks to human subjects or others.  
8.2 
Informed Consent 
In obtaining and documenting informed consent, the investigators will comply with all applicable local 
and/or domestic regulatory requirements and will adhere to Good Clinical Practices and to all ethical 
principles from the Declaration of Helsinki. A trained research staff person will conduct the informed 
consent process. Written informed consent will be obtained individually from each participant. Staff will 
explain the study, read the consent form, and answer any questions the participant may have. Consent 
information will describe the purpose of the study, the procedures to be followed, and the risks and 
benefits of participation, in accordance with all applicable regulations. We will translate the forms into the 
local language (Kiswahili) and verify the accuracy of the translation by performing an independent back-
translation. The consent process will occur either in English or the local language (Kiswahili) depending 
on the participant’s preference. We will perform paper-based and/or electronic-based consenting of 
participants. For the electronic version, we will program the complete consent form with signature pages 
onto tablets and participants will read along on the tablet during the consenting process. The study team 
member conducting consent will allow the participant time to ask any questions that they may have before 
signing the consent form. After we have ensured that participants have read and understood the consent 
forms, we will ask them to append their signature on the tablet. The signature will be stored electronically. 
In addition, any participant who wants their consent form to take home will have a paper copy printed and 
given to them. At each visit after enrollment, participants will have the opportunity to ask questions and 
the study staff will remind them their participation is voluntary. Participants will be informed that they may 
withdraw from any of the research procedures at any time, without it affecting the care they receive at 
the clinic. 
8.3 
Voluntary Participation 
The consenting process will emphasize and give information that study participation is voluntary and that 
the participant can withdraw from the study at any time without losing the care they would otherwise 
receive.  
8.4 
Potential Risks to Human Subjects 
Safety assessment will be measured in all participants: serious adverse events (SAEs), related Grade 3 
and 4 AEs and discontinuations, and side effects. The medical risks of blood collection and vaginal tissue 
collection are small, with some anticipated mild discomfort from vaginal speculum insertion, and 
venipuncture. Participants may become embarrassed, worried, or anxious while undergoing pelvic exams 
for collection of samples. 
Risks related to non-daily TAF-FTC PrEP dosing 
Descovy® is approved by the U.S. Food and Drug Administration for PrEP use in cisgender men and 
transgender women18. However, Descovy® is not yet indicated in at risk cisgender women because the 
effectiveness in cisgender women has not been evaluated. Only daily FTC/TDF PrEP is currently 
approved for PrEP in cisgender women but large studies of Descovy® (F/TAF) PrEP for cisgender 
women are currently planned or ongoing in African cisgender women. We have carefully considered the 
risk for TAF-FTC PrEP and non-daily dosing (i.e., 2 or 4 doses per week) in cisgender women, including 
the potential for risk of HIV infection. The non-daily dosing is needed to help investigate and demonstrate 
dose proportionality of TFV and TFV-DP concentrations. For people living with HIV, Descovy® has been 
approved by the FDA for treatment of HIV in combination with other antiretroviral drugs since 201620, with 
very favorable safety profile compared to FTC/TDF. As detailed in the eligibility section, to minimize risks 

 
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only cisgender women at low risk of HIV based on the Kenya guidelines for PrEP will be enrolled and 
cisgender women will receive a full package of HIV prevention, including risk reduction counseling, 
condoms and STI treatment at each visit. We will also perform monthly HIV testing. We will use Kenya 
national PrEP guidelines to guide identification of cisgender women at elevated risk of HIV to guide 
recruitment into this study. Cisgender women found to  be at risk for HIV through the screening process 
will be given PrEP at the clinic if interested or referred at their clinic of choice. Each visit will include risk-
reduction counseling for all cisgender women. All participants in this study will have HIV test at baseline 
and then every 4 weeks and study drug will be immediately discontinue in case of seroconversion. 
Risks related to TAF-FTC PrEP 
Study medication risks and side effects related to TAF-based PrEP include: occurring in a minority of 
individuals taking PrEP - gastrointestinal intolerance, such as nausea, diarrhea or vomiting, flatulence 
typically during the first month after PrEP initiation; rare but serious side effects of lactic acidosis/ severe 
hepatomegaly with steatosis, renal impairment, including cases of acute renal failure and Fanconi’s 
syndrome (renal tubular injury with severe hypophosphatemia), increase in bone metabolism leading to 
osteopenia, and hypersensitivity reaction.  Because TAF achieves lower blood concentrations but higher 
concentrations in tissue after dosing, these risks are hypothesized to be lower compared FTC/TDF PrEP, 
the currently approved oral PrEP regimen.  
Risks from vaginal biopsy 
Vaginal tissue biopsy is an in invasive procedure and we have carefully considered the risk involved 
including some discomfort, pain and potential for bleeding and burden on cisgender women. Sampling 
vaginal tissue is important to fully characterize HIV protection in cisgender women since it is a tissue of 
relevance to the acquisition of HIV infection for cisgender women and will help to define early drug kinetics 
and how soon drugs accumulate in vaginal tissue from PrEP initiation until steady state. To minimize 
risks, we have carefully considered sampling schedule to minimize risk associated with this procedure 
and burden on cisgender women: Each participant will provide only one biopsy in a 4-week period by 
sampling unique cisgender women (i.e., for each planned tissue sampling visit different cisgender women 
will be sampled  at day 4 and day 7). All participants will provide a vaginal tissue sample for week 4 and 
8. 
Social harm and stigma risks 
We have considered the risk of social harm related to both DOT study medication use and frequent clinic 
visits, including risks of depression/anxiety and disclosure and stigma. Our extensive experience with 
successful and safe longitudinal follow-up of cisgender women at risk mitigates some of this risk, and we 
will measure social harms and provide/refer services when harms are reported. Participants also may 
become embarrassed, worried, or anxious while completing surveys or interviews regarding sexual 
behavior and acceptability. Counseling will be provided by clinical study staff who have been trained in 
specific issues related to STI/HIV risk, PrEP, STI/HIV acquisition, and care of HIV infected cisgender 
women, including stigma, blame, methods to avoid transmission, and available support services.  
Behavior disinhibition risks 
The potential for behavior disinhibition may exist as a result of PrEP and is an important outcome, 
especially given the potential for some participant to receive less than daily dosing of PrEP. This study is 
specifically recruiting cisgender women at low risk of HIV, which reduces this risk. Nevertheless, we will 
use brief standardized questionnaires, which we have used for prior studies in cisgender women to 
explore partner number, sexual frequency, and condom use over time.  
Privacy and confidentiality risks 
Although study site will make every effort to protect participant privacy and confidentiality, it is possible 
that participants' involvement in the study could become known to others. For example, participants could 
be treated unfairly or discriminated against, or could have problems being accepted by their families 

 
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and/or communities. We have extensive experience with the strategies to minimize the potential for social 
harms in populations participating in HIV prevention studies. 
Risks from other study procedures 
Blood for safety labs and study pharmacokinetic samples will be collected from each subject during the 
study period. Blood will be collected from an arm vein and by fingerstick. Risks of blood draws include 
pain when the needle or lancet pierces the skin, bruising, and/or infection. The blood volumes are well 
below the maximal volumes set for blood donations and clinical research in 18 weeks. Approximately 100 
strands of hair will be cut from the back portion of the scalp on multiple occasions. This could leave a 
noticeable spot from where the hair was cut. 
8.5 
Approaches to Minimize Risks 
Protection of risks related to non-daily PrEP dosing 
We have carefully considered the risk associated with using non-daily dosing for PrEP (i.e., 2 or 4 doses 
per week) in non-pregnant cisgender women and the potential for behavior disinhibition as a result of 
PrEP is an important outcome. We will make all efforts to enroll only healthy cisgender women volunteers 
deemed at low risk for HIV. We will rely on Kenya national guidelines as well as published HIV risk scores 
(Voice risk) to guide identification of cisgender women who may be at elevated risk of HIV to guide 
recruitment into this study ─those found to be at elevated risk for HIV will be immediately linked for PrEP 
and other prevention services here at the Thika site or at the participants’ clinic of choice. Each visit will 
include risk-reduction counseling for all cisgender women. All participants in this study will have an HIV 
test at baseline and then every 4 weeks, with immediate discontinuation of PrEP in case of HIV 
seroconversion. 
Protection against risks related to TAF-FTC PrEP 
All participants will have HIV testing, creatinine testing, hepatitis B, and urine pregnancy testing at 
baseline. Only cisgender women with creatinine clearance >60 mL/min and uninfected with hepatitis B 
will be enrolled. Testing of volunteers for HBV-infection is conducted to protect subjects from HBV-
associated hepatitis flares when study  drugs are withdrawn. Breastfeeding will not be allowed to prevent 
risks to nursing infants. We will exclude subjects who have serious underlying illnesses such as cancer 
and heart disease. All participants will be counseled about potential side effects at enrollment and at each 
follow up visit, and they will be reminded that the side effects are self-limiting within 1-2 weeks. Subjects 
will be followed with clinical laboratories at entry and 10 weeks (serum creatinine, complete hematology, 
monthly pregnancy urine test) and more frequently with interviews to assess tolerability and safety over 
the course of the study, including during directly observed dosing. Participants will be tested for HIV 
infection at any point during the study as needed, and prior to and at the final visits of the dosing periods. 
The most likely risks associated with TAF-FTC in HIV-negative persons appear to be reversible 
gastrointestinal complaints, headache, and/or weight decrease. These side effects are most likely mild 
and reversible.45 There is a remote risk of serious side effects including renal injury, lactic acidosis with 
hepatomegaly and steatosis, bone pathology, hypophosphatemia, hepatitis, pancreatitis, and there are 
possible side effects not listed here, or possible unforeseen long-term complications. We believe the risk 
of these serious side effects is remote given the rarity of the events during long-term treatment and PrEP 
in previous studies. We have designed the inclusion and exclusion criteria to exclude subjects who might 
be at higher risk of these toxicities. We have also designed a monitoring strategy for early detection of 
side effects and for quick study drug discontinuation, if needed, to protect subjects.   
Protection of risk related to vaginal tissue biopsy 
We have also carefully considered our sampling schedule to minimize risk associated with vaginal tissue 
biopsy and burden on cisgender women and will take the following measures: 1) Only low HIV risk non-
pregnant cisgender women will provide vaginal tissue samples 2) Each participant will provide only one 

 
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biopsy in a 4-week period. We will sample cisgender women as two separate groups during the first 
week, i.e. half of participants on day 1 and the other half on day 7. This will ensure sufficient time between 
the week 1 and week 4 sample. All participants will provide vaginal tissues samples during weeks 4 and 
8. Participants will be counseled to avoid sex in ~7 days after biopsy. 
Reducing social harm risks 
In addition to protecting the privacy of participants, as described above, we will monitor for social harms. 
Social harms will be recorded on separate case report forms. Severe unexpected social harms will be 
considered unexpected problems and reported to the IRB according to local regulations.  Social harms 
will be included on summary reports for the PSRT, as described in this protocol.  
Reducing risks behavior disinhibition 
We will use brief standardized questionnaires, which we have used for prior studies in cisgender women 
to explore partner number, sexual frequency, and condom use over time. Each visit will include risk-
reduction counseling for all cisgender women and cisgender women will be provided with condoms.   
Reducing risks from other study procedures 
Blood will be collected from an arm vein, and/or by finger stick, by trained staff at the study site according 
to standard medical procedures. Hematology will be monitored. The hair that is cut will be taken from 
underneath the top layer of hair to minimize the ability to see where the hair was cut from and to avoid 
sun-bleached hair. 
All participants in this study will have an HIV test at baseline and then every 4 weeks. All data received 
at the University of Washington will be labeled only with participant ID number and no identifying 
information will be transmitted. The study team has extensive experience with counseling about HIV risk, 
PrEP (and ART), and strategies for HIV prevention in general. In addition to PrEP and STI treatments, 
condoms will be provided to all participants by the study site and will follow Kenya clinical guidelines. 
Counseling about safe sex and medication adherence for prevention will include messaging describing 
the benefits of all strategies, based on evolving available data and national policies for HIV prevention.  
For data collection, standardized questionnaires will be used that will include questions on sensitive 
topics, including sexual behavior, and stigma. We have extensive experience with these questionnaires 
from our prior studies and the expertise and counseling resources required to attend to study participants. 
We have extensive experience with management of potential social harms, through our prevention 
studies. The risks from the anticipated activities will be no greater than in our previous studies; in fact, 
given the proven prevention benefits of PrEP and now normalized national roll-out in Kenya, risks are 
anticipated to be less than in some of our prior studies.  
8.6 
Benefits. 
Participants will benefit from ongoing access to standard clinical care as part of this study. Additionally, 
participants or others may benefit in the future from information learned in this study, including its 
contribution to our understanding of HIV prevention and effective PrEP use in cisgender women in Africa. 
While enrolled in the study participants will have access to all services available to those not in the study, 
including access to counseling for reducing risk of getting HIV from their sexual partner, and provision of 
free condoms. For care and treatment that is not available at the clinic, study staff will inform and refer 
participants to other health facilities where care and treatment may be available. 
8.7 
Treatment for Injury 
Participants will be asked to inform the clinic staff if they feel they have been injured because of taking 
part in the study. Injuries may also be identified during laboratory testing, medical histories, and physical 
examinations. Treatment for adverse events related to study participation will be provided by the 
treatment clinic. If treatment is required that is beyond the capacity of the clinic, the clinic staff will refer 

 
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the participant to appropriate services or organizations that can provide care for the injury.  
8.8 
Study Records 
Study investigators will maintain, and store in a secure manner, complete, accurate, and current study 
records throughout the study. Study records include administrative documentation and regulatory 
documentation as well as documentation related to each participant enrolled in the cohort, including 
informed consent forms, data forms, documentations of all contacts with the participant, and all other 
source documents.   
8.9 
Confidentiality 
Every effort will be made to protect participant privacy and confidentiality to the extent possible. At the 
pharmacy, clients will perform HIV self-testing in a private space within the pharmacy area to encourage 
privacy during the self-testing process. Records pertaining to clinical and programmatic provision of PrEP 
(i.e. not related to research) will remain at the public health clinic and maintained by MOH staff at clinic 
as per standard of care practices. 
All research-related information will be stored securely at the research clinic in Thika. Research data 
collection, administrative forms, laboratory specimens, and other reports will be identified only by a coded 
number to maintain participant confidentiality. All research records that contain names or other personal 
identifiers, such as informed consent forms, will be stored separately in locked cabinets at the research 
clinic in Thika away from study records identified by code number. All local databases will be secured 
with password-protected access systems and only project staff with permission will have access to them. 
Data collected or abstracted from clinical forms during the course of this project will be entered 
electronically on tablets via REDCap collection software and transmitted to in aggregate to a web server 
via encrypted secure socket layer (SSL) and only accessible by authenticated users. All computers, 
tablets (used for data collection), and individual study databases will be encrypted, and password 
protected. 
Participants’ study information will not be released without their written permission, except as necessary 
for oversight by: 
§ 
Kenya Ministry of Health 
§ 
Kenya Medical Research Institute 
§ 
University of Washington 
§ 
University of Colorado 
§ 
Gilead Sciences 
§ 
U.S., local, and international regulatory entities 
 
8.10 Reimbursement 
Participants will receive reimbursement for their transport for visiting the clinic, and 400 KSh for their 
time and effort at each scheduled study visit. All visits that include collection of vaginal biopsies will be 
reimbursed 2000 KSh and visits that include collection of vaginal swabs only will be reimbursed 1000 
KSh.  
8.11 Communicable Disease Reporting Requirements  
Study staff will comply with all applicable local requirements to report communicable diseases identified 
among study participants to local health authorities. Participants will be made aware of all reporting 
requirements during the study informed consent process.  
8.12 Reports of Sexual Abuse 
Reporting requirements and confidentiality of minor’s information should be detailed in site specific 
consents/assents and SOPs.  

 
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8.13 Study Discontinuation  
The study also may be discontinued at any time by government or regulatory authorities, or site 
IRBs/ECs. 
Subjects may withdraw from the study at any time. Depending on the time point and circumstances of a 
subject’s withdrawal they will be asked to complete/offer an “Early Discontinuation/Exit Visit” to confirm 
safety and health status as the time of withdrawal. The study investigators can remove a subject at any 
time if they deem that the study is no longer in the subject’s best interest or the subject is not adhering to 
the protocol. Discontinuation of a subject by the PI/Co-I(s) could be a result of but is not limited to the 
following:  
– Subjects who become incarcerated while on the study. 
– Subjects who acquire other infectious diseases (i.e. not HIV) while in the study will be reviewed 
by the PI/PSRT to confirm subject is still considered low-risk for HIV infection (See Exclusion 
criterion) This determination will be done by the PI/study physician.   
– Subjects who are deemed to be non-compliant with the study medication(s) and/or procedures 
(e.g. 2 consecutive missed study visits or medication doses) may be discontinued from the study 
by the PI.  
– Permanent study drug discontinuations for toxicity were described above. These participants will 
be followed until the completion of scheduled protocol study duration.  
– Subjects who require an exclusionary medication during the study will be discussed among the 
PSRT. Participant’s continued study involvement will be determined the PSRT and PI’s.  
The PSRT will be consulted if and when these circumstances arise. 
9 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
9.1 
Laboratory evaluations and specimen collections 
The following safety and monitoring laboratories will be collected at regular intervals during the study as 
described above: complete hematology panels, pregnancy tests (urine),  HIV tests (rapid or regular), 
serum creatinine (estimated creatinine clearance), and HBV surface antigen test. The HIV and HBV tests 
will be used to screen HIV-negative volunteers for inclusion in the study. The tests are provided according 
to established laboratory procedures at site. These clinical laboratories/sites conform to CAP and/or 
CLIA-regulations, and the results will be posted to the participant’s medical record as positive or negative.  
All pharmacokinetics samples will be collected, processed, and stored according to standard operating 
procedures developed by the Colorado Antiviral Pharmacology Laboratory. On each pharmacokinetics 
sample visit day, samples will be collected without regard to the dosing time within each day (i.e., 
sampling is at convenience times rather than troughs). The only exception will be at the entry visit, where 
samples are to be obtained pre-dose. We will take a comprehensive approach to establish benchmark 
adherence-concentration thresholds for cisgender women using daily DOT TAF/FTC PrEP by collecting 
samples for pharmacokinetic measurements in multiple biologic matrices: plasma, whole blood, DBS, 
PBMCs, vaginal swabs, and vaginal tissue  and by archiving urine and hair samples. All cisgender women 
will contribute to this comprehensive assessment during the study participation duration of up to 18 weeks 
(10 weeks of DOT PrEP and 8 weeks post DOT PrEP for post drug kinetics). Within each group, we will 
collect pharmacokinetic samples (plasma, whole blood, DBS, PBMCs) to measure the respective 
concentrations of TAF/FTC moieties at day 4 and weekly up to 8 weeks with daily DOT PrEP dosing and 
vaginal tissue at day 4, week 1, 4, and 8.  

 
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9.2 
Specimen preparation, handling, and shipping  
All pharmacokinetic samples will be collected, processed, stored, and shipped according to standard 
operating procedures developed by the Colorado Antiviral Pharmacology Laboratory. Specimens will be 
collected by skilled study personnel in accordance with local study site policies and procedures. All 
specimen collections are described in this protocol. 
Samples that are shipped to outside entities are regulated by the International Air Transportation 
Association. Such training and certification of study personnel is handled through the University of 
Colorado Denver Environmental Health and Safety Division. This training is required on a biannual basis. 
This protocol follows IATA Guidance 48-DGR when air transport is required.  
9.3 
Specimen Storage and Possible Future Research Testing 
We will store blood, urine, hair, and genital specimens collected in this study for future testing. Study 
participants will be asked to provide written informed consent for their specimens to be stored after the 
end of the study for possible future testing related to the study objectives. The specimens of participants 
who do not consent to long-term storage and additional testing will be destroyed after all protocol-related 
testing has been completed; sample destruction must be coordinated with the protocol leadership and 
PSRT. 
9.4 
Quantification of drug concentrations 
Drug concentrations will be determined using analytical methodologies (such as liquid chromatography 
tandem mass spectrometry (LC/MS) methods) described previously 6, 46 and validated for each biological 
matrix of origin (plasma, whole blood, DBS, PBMCs) by the Colorado Antiviral Pharmacology Laboratory 
(CLIA 06D1094710; PI: Dr. Anderson )47-50. The CLIA laboratory participates in the NIH-supported Clinical 
Pharmacology Quality Assurance program of assay method external review and approval and periodic 
proficiency testing51. All assays were validated based on the FDA recommendations for Industry, 
Bioanalytical Method Validation and met all acceptability criteria. Validation metrics include precision, 
accuracy, stability, and matrix effects. The laboratory has a long history of innovative and lasting 
contributions to antiviral clinical-translational research including development and validation of 
methodology for intracellular TVF-DP and FTC-DP in various cell types from human subjects. Data from 
this assay was used to support the pharmacology measurements for the iPrEx6 and DISCOVER studies 
that helped lead to the FDA-indication of daily TDF/FTC and TAF/FTC PrEP for MSM and the 
pharmacokinetic study that developed an estimate of protective concentrations of tenofovir as a surrogate 
of HIV protection in MSM. We will use the same methods to support the current proposal. These assays 
have been implemented in a number of preclinical, clinical, and registration trials. 
9.5 
Biohazard Containment 
All study personnel will follow universal precautions, as recommended by the Center for Disease Control 
and the NIH including the appropriate disposal of needles, etc., and human waste products to prevent 
the accidental transmission of blood borne pathogens. Training as such will be documented in study 
personnel’s records. Study specific SOPs will outline procedures for safe procurement and handling of 
study specimens. All dangerous goods materials, including diagnostic specimens and infectious 
substances, will be transported according to instructions detailed in the International Air Transport 
Association Dangerous Goods Regulations. 
10 ADMINISTRATIVE PROCEDURES  
10.1 Study activation 
Pending successful protocol registration and submission of all required documents, the protocol chair will 
“activate” a site. Study implementation (screening and enrollment) may not be initiated until a study 
activation notice is provided to the site by the protocol chair. In addition, if study “activation” is determined 
to be necessary for any subsequent amendments, study implementation may not be initiated until a study 
activation notice is provided to the site by the protocol chair. 

 
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10.2 Study coordination 
Study implementation will be directed by this protocol. Close coordination between protocol team 
members will be necessary to track study progress, respond to queries about proper study 
implementation, and address other issues in a timely manner. Rates of accrual, adherence, follow-up, 
and AE incidence will be monitored closely by the protocol team. The Protocol Co-Chairs and Protocol 
Biostatistician will address issues related to study eligibility and AE management and reporting as needed 
to assure consistent case management, documentation, and information-sharing across sites. 
10.2.1 Data storage and management responsibilities 
Data will be managed by study personnel at the site and University of Washington. Clinical and baseline 
data collected during the course of this study will be collected electronically via REDCap data collection 
software. Quantitative survey data, clinic and pharmacy records will be abstracted in real time to tablet-
based case report forms and entered into an electronic database in REDCap. Automated legal range 
checks will be programmed to reduce data entry errors and internal quality control reports will be run 
monthly. Our team has experience using this data capture method in other studies of HIV prevention. 
Data will be uploaded daily via REDCap Survey and will be transported via secure socket layer (SSL) 
and only accessible by authenticated users. Weekly reports will be generated to monitor study progress 
and troubleshoot problems. All computers, tablets (used for primary data collection), and individual study 
databases will be encrypted, and password protected. Participants will be assigned a non-identifiable 
study code upon enrollment. Study analysts will receive only coded data. The links to patient identifiers 
will be retained in a password protected file on an encrypted computer.   
10.2.2 Source Documents and Access to Source Data/Documents 
Source documents will be kept in subject study records (binders). Documentation will be sufficient such 
that study data can be reconstructed, evaluated, and validated for all clinical activities during the trial.  
The goals are to ensure that protocol, IRBs, and funder requirements and standards are adhered to and 
that all data will be verifiable from the written source document and will create an audit trail to verify that 
data is present, complete and accurate. Source data consists of all information in original records and 
certified copies of original records.  The “ALCOA” method is used to achieve and maintain data quality: 
Attributable, Legible, Contemporaneous, Original and Accurate. 
10.2.3 Data monitoring 
The study team will review project progress in the weekly operational meeting and monthly for an all-
team meeting; teleconference or internet-based mechanisms (Skype, Zoom) will be used for these 
meetings. The Seattle-based data manager will conduct data monitoring weekly via routine operational 
reports to track participant accrual, retention, completion of study procedures, and a check of eligibility 
criteria for all enrolled participants. Data quality checks will be conducted monthly to identify missing 
values, inconsistent information, and unacceptable lags between the timing of study visits and data 
updates to the web-based data entry platform. Twice per year, the PI and a Seattle-based research 
manager will travel to study site in Kenya to conduct an on-site assessment of data and laboratory quality; 
site Co-Investigators will perform day-to-day oversight of quality for the project. 
The study and updated information will be registered on ClinicalTrials.gov according to UW Office of 
Sponsored Program and NIH policies.  
10.2.4 Quality control and Quality assurance 
A program for quality assurance and quality control has been developed as a system of self- monitoring 
to promote the integrity and quality of the study. The program is detailed in an SOP.  
10.3 Study monitoring 
Study monitors will visit the site to: 
• 
Verify compliance with human subjects and other research regulations and guidelines;  

 
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• 
Assess adherence to the study protocol, study-specific procedures manual, and local counseling 
practices; and 
• 
Confirm the quality and accuracy of information collected at the study site and entered into the 
study database. 
Site investigators will allow study monitors to inspect study facilities and documentation (e.g., ICFs, clinic 
and laboratory records, other source documents, CRFs), as well as observe the performance of study 
procedures. Investigators also will allow inspection of all study-related documentation by authorized 
representatives of the UW, NIAID, site IRBs/ECs, US regulatory authorities (OHRP), Kenya MOH, PPB, 
and other U.S., local, and international regulatory entities. A site visit log will be maintained at each study 
site to document all visits.  
 
The International Clinical Research Center (ICRC) at the University of Washington will provide regular 
study monitoring for the Thika site. The Study Monitor will be a Senior Research Manager at ICRC. The 
Research Manager will have a graduate degree and will be experienced in site monitoring activities. The 
site monitor will conduct on site reviews of source documents, participant records, regulatory files, 
facilities, laboratories and the dispensing pharmacy. The signed informed consent documents will be 
made available for review for compliance with GCP requirements. Original source documents will be 
made available to verify all inclusion/exclusion criteria. Individual participant’s source documents will also 
be available for review and comparison to protocol requirements and the completed case report forms 
(CRFs). Through this detailed review, monitoring will focus on the following key processes of the study: 
• 
Informed consent process 
• 
Study eligibility criteria met for all participants 
• 
Timely completion of study CRFs 
• 
Sample collection and handling in accordance to Protocol and SOP(s)  
• 
Review of data management procedure 
• 
Reporting of adverse events and protocols violations according to SOP(s) 
• 
Follow up assessments and procedures 
• 
Product accountability  
• 
Regulatory documents on file  
Monitoring visits may be conducted on-site or remotely. Remote visits may include remote source 
document verification using methods specified for this purpose by the UW or funder. Remote monitoring 
visits may be performed in place of, or in addition to onsite visits to ensure the safety of study participants 
and data integrity52. The site will make available study documents for site monitors to review utilizing a 
secure platform that is HIPAA and 21 CFR Part 11 compliant. Potential platform options include: Veeva 
SiteVault, site-controlled SharePoint or cloud-based portal, direct access to Electronic Medical Record 
(EMR), and Medidata Rave Imaging Solution. Other secure platforms that are 21 CFR Part 11 compliant 
may be utilized. 
10.4 Investigator’s Records 
The Investigator will maintain, and store in a secure manner, complete, accurate, and current study 
records throughout the study. Completion of a clinical research study occurs when the following activities 
have been completed: 
 
• All research-related interventions or interactions with human subjects (e.g. when all subjects are 
off study);  
• All protocol-required data collection of identifiable private information described in the IRB/EC-
approved research plan;  
• All analysis of identifiable private information described in the IRB/EC-approved research plan;  
• Primary analysis of either identifiable private or de-identified information.  
 

 
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Study records include administrative documentation — including protocol registration documents and all 
reports and correspondence relating to the study — as well as documentation related to each participant 
screened and/or enrolled in the study — including ICFs, locator forms, CRFs, notations of all contacts 
with the participant, and all other source documents. 
10.5 Use of Information and Publications 
The Principal Investigator will have oversight of publications and presentations emanating from this study. 
The Principal Investigator will ensure that authorship and authorship order is equitable with respect to 
the effort contributed to the work. Contributing effort that justifies authorship includes participation in the 
design of the study and assays used in the study; participation in carrying out the study; participation in 
analyzing the data; and participation in writing the manuscript or presentation. Trainees or students who 
contribute work will be equally eligible for authorship. First authorship will reflect the individual who 
contributes the most effort and writing to the manuscript. First authorship may be split if two individuals 
contributed to the effort equally. Senior authorship will reflect the individual who provided the scientific 
oversight and direction for the manuscript or presentation. 
10.6 Resource sharing and dissemination plan 
10.6.1 Resource Sharing:   
For all data generated during the course of this project, we will follow the prevailing standards and 
guidelines in documenting and depositing datasets. We will make quality-controlled raw data as well as 
processed data used in publications available. As described in the grant application, protocols and 
workflows will be implemented exactly as described and documented such that other groups will be able 
to precisely reproduce results from the raw data. 
The study personnel assigned to the project, including KEMRI-based and University of Washington-
based investigators, will disseminate results from this research through presentations at public lectures, 
scientific institutions and meetings, and/or publication in major journals.  
10.6.2 Data Sharing Plan 
Intellectual property, data and materials generated under the project will be disseminated in accordance 
with KEMRI, University of Washington, University of Colorado, and Gilead policies. Depending on such 
policies, materials may be transferred to others under the terms of a material transfer agreement. Access 
to databases and associated software tools generated under the project will be available for educational, 
research, and non-profit purposes. Such access will be provided using web-based applications, as 
appropriate. Publication of data shall occur during the project, if appropriate, or at the end of the project, 
consistent with normal scientific practices. Research data that documents, supports, and validates 
research findings will be made available after the main findings from the final research data set have 
been accepted for publication. Such research data will be modified to prevent the disclosure of personal 
identifiers to remain in compliance with the Protection of Human Subjects guidelines. 
10.6.3 Collaborative research 
The proposed project is a collaborative effort between Gilead, UW, UC, and KEMRI. The aforementioned 
institutions will jointly share ownership of the data. Authorship on publications, conference presentations, 
abstracts and other materials generated from this program will reflect contribution to design, execution 
and analysis of the program data. 
10.6.4 Dissemination plan 
Dissemination of study results will follow principles of good participatory practice. Study results will be 
disseminated through presentations to stakeholders and policymakers and published in conference 
abstracts and peer-reviewed journals. We will disseminate the results from this research as broadly as 
possible. First, we will publish our results in Open Access journals, if appropriate. Second, we will post 

 
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author PDFs of our manuscripts on our respective websites in accordance with the copyright rules of the 
journals. 
10.6.5 Presentations 
We expect that all the research personnel will attend national conferences periodically and present the 
results from this research to the scientific community. Because of the multidisciplinary nature of the work, 
different group members will present at various conferences, such as the Conference on Retrovirus and 
Opportunistic Infections, International AIDS Society, and Kenya-based conferences, which focus on the 
appropriate aspects of our research.  
The study team for this project is committed to the public dissemination of clinical trial results to trial 
participants, local stakeholders in Kenya, the global scientific community, and US, Kenyan, and global 
policymakers. Dissemination of study results will follow principles of good participatory practice. The 
clinical trial will be registered with ClinicalTrials.gov prior to initiation and results will be updated there in 
a timely fashion. Results will be published in conference abstracts and peer-reviewed journals. Study 
results will be disseminated through presentations to local stakeholders and policymakers in Kenya, 
including the Ministry of Health. 
11 TIMELINES  
 We have planned for an efficient time-sensitive two-year project, given the timely nature of the question 
(Table 7). 
12 EXPECTED APPLICATION OF RESULTS 
The study will be the first to define TAF-PrEP adherence-concentration thresholds in Africa cisgender 
women, a population facing significant burden of incident HIV infection. Knowledge gained from the 
proposed study will include key concentrations of TAF-PrEP medications associated with HIV protection 
and the required adherence to achieve those concentrations for cisgender women. In addition, data from 
this work will help to estimate the quantitative concentrations of PrEP medication associated with 
protection against HIV in cisgender women and adherence required to generate those concentrations. 
The results of this work will have immediate implications for the global TAF-PrEP programs among 
cisgender women. 
 
Table 7 
 
Project Years 
Y1 
Y2 
AIM 
MILESTONE 
Quarter 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Funding 
Funding Announced 
 
 
 
 
 
 
 
 
Protocol Planning 
Protocol Development 
 
 
 
 
 
 
 
 
IRB Submission, SOP development 
 
 
 
 
 
 
 
 
Protocol Execution 
Enrollment, follow up in DOT study, 
pharmacokinetics sample collection 
 
 
 
 
 
 
 
 
Regulatory application from MOH and IRB 
to ship samples 
 
 
 
 
 
 
 
 
Ship DOT pharmacokinetic samples 
 
 
 
 
 
 
 
 
Test DOT study samples 
 
 
 
 
 
 
 
 
Statistical analyses and compilation of full 
spectrum of results 
 
 
 
 
 
 
 
 
Dissemination 
Writing and results dissemination  
 
 
 
 
 
 
 
 
 

 
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13 STUDY LIMITATIONS  
The study team recognizes potential limitation of the proposed work which may include: 1) Part of 
preliminary data are not from DOT studies and that observed effects might be due to correlation between 
MEMS and blood levels and not related to pharmacokinetic differences between US male and African 
cisgender women blood levels. However, we take confidence in fact that our pregnancy data from the 
same population have been replicated by the IMPAACT 2009 study; 2) Intensive sampling for individual 
PK parameters is not planned as that is well defined. DBS exhibits a long half-life and is not suited for 
intensive PK. Nevertheless, while plasma steady-state levels do not pinpoint the mechanism for PK 
differences, they will indicate whether or not recent PK exposure differs and by how much. Furthermore, 
population PK models will be developed to determine individual-level PK in plasma. 
 

 
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10.1097/QAD.0000000000000493. PMCID: 4266161. 
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outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial. 
JAMA. 2014;312(4):362-71. doi: 10.1001/jama.2014.8735. PMCID: 4362516. 
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N. R. Mugo, K. Ngure, M. Kiragu, E. Irungu and N. Kilonzo. The preexposure prophylaxis revolution; from 
clinical trials to programmatic implementation. Curr Opin HIV AIDS. 2016;11(1):80-6. 
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K. K. Mugwanya, D. Donnell, C. Celum, K. K. Thomas, P. Ndase, N. Mugo, E. Katabira, K. Ngure, J. M. 
Baeten and Partners PrEP Study Team. Sexual behaviour of heterosexual men and women receiving 
antiretroviral pre-exposure prophylaxis for HIV prevention: A longitudinal analysis. Lancet Infect Dis. 
2013;13(12):1021-8. PMCID: 3920826. 
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K. Ngure, R. Heffron, N. Mugo, E. Irungu, C. Celum and J. M. Baeten. Successful increase in contraceptive 
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K. Ngure, R. Heffron, N. Mugo, K. A. Thomson, E. Irungu, N. Njuguna, L. Mwaniki, C. Celum and J. M. 
Baeten. Feasibility and acceptability of HIV self-testing among pre-exposure prophylaxis users in Kenya. J Int 
AIDS Soc. 2017;20(1):1-8. 
36. 
S. M. Baxi, A. Liu, P. Bacchetti, G. Mutua, E. J. Sanders, F. M. Kibengo, J. E. Haberer, J. Rooney, C. W. 
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Defic Syndr. 2015;68(1):13-20. PMCID: PMC4262724. 
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V. S. Sethuraman, S. Leonov, L. Squassante, T. R. Mitchell and M. D. Hale. Sample size calculation for the 
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Population Pharmacokinetic-Pharmacogenetic Analysis of Atazanavir. AIDS Res Hum Retroviruses. 2012. 
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J. J. Kiser, C. L. Aquilante, P. L. Anderson, T. M. King, M. L. Carten and C. V. Fletcher. Clinical and genetic 
determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J Acquir Immune 
Defic Syndr. 2008;47(3):298-303. 
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Therapy. Antimicrob Agents Chemother. 2018;62(1). PMCID: PMC5740314. 
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A. Y. Liu, Q. Yang, Y. Huang, P. Bacchetti, P. L. Anderson, C. Jin, K. Goggin, K. Stojanovski, R. Grant, S. P. 
Buchbinder, R. M. Greenblatt and M. Gandhi. Strong relationship between oral dose and tenofovir hair levels in 
a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP). PLoS One. 
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G. Sciences. TRUVADA® (EMTRICITABINE/TENOFOVIR DISOPROXIL FUMARATE) FOR PRE-EXPOSURE 
PROPHYLAXIS OF HIV-1; 2012 [updated 2012 May 10; cited]; Available from: 
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LC-MS/MS detection. J Pharm Biomed Anal. 2011;56(2):390-401. PMCID: PMC3153375. 
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Patterson, A. M. Minnis, S. Gandham, K. Gomez, B. A. Richardson and N. N. Bumpus. MTN-001: randomized 
pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other 
compartments. PLoS One. 2013;8(1):e55013. PMCID: PMC3559346. 
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randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity 
following application of 1% tenofovir gel. PLoS One. 2011;6(1):e16475. PMCID: PMC3026837. 
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Bushman, J. Kiser and P. L. Anderson. Quantitation of tenofovir and emtricitabine in dried blood spots (DBS) with 
LC-MS/MS. J Pharm Biomed Anal. 2014;88:144-51. PMCID: PMC3842403. 
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15 APPENDIXES— STUDY CONSENT FORM TEMPLATES 
Study Title: Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan 
Cisgender women 
Study Screening Informed Consent Form 
Version 1.1, August 15, 2022 
INVESTIGATORS 
Investigator 
Title 
Institution 
Telephone  
Kenneth Mugwanya 
MBChB, MS, PhD 
University of Washington 
001 206-520-3886 
Nelly Mugo 
MBChB, M.Med, MPH 
Kenya Medical Research 
Institute 
067 2222561 
Peter Anderson 
PharmD 
University of Colorado 
001 303-724-6128 
Elizabeth Irungu 
MBChB, MPH, PhD 
Kenya Medical Research 
Institute 
067 2222561 
Catherine Kiptinness B. Pharm, MPH 
Kenya Medical Research 
Institute  
067 2222561 
STUDY LOCATION: The study will be conducted at Thika.  
You are being asked to take part in a research study. The box below tells you important things 
you should think about before deciding to join the study.  We will provide more detailed information 
below the box. Please ask questions about any of the information before you decide whether to 
participate. You may also wish to talk to others (for example, your family, friends, or your doctor) 
about this study, before agreeing to join.    
Key Information for You to Consider 
• 
Voluntary Consent. You are being asked to volunteer for a research study.  It is up to 
you whether you choose to participate or not. There are no penalties and you will not lose 
anything if you decide not to joint or if after you join, you decide to quit.  
• 
Purpose. We are doing this research to find out more about the medication called 
Tenofovir alafenamide /Emtricitabine (TAF/FTC Descovy®). Descovy® has been shown 
to lower the chances of getting HIV in men.This is also called preexposure prophylaxis or 
PrEP.  Research studies are ongoing to understand how Descovy® PrEP works to 
prevent in women. We want to learn more about the levels of PrEP in blood and other 
body parts when used by women. 
• 
Duration. Your part of the study will last for up to about up to 4 ½ months; up to 2 and 
half months when taking medication and 2 months after you stop. 
• 
Procedures and Activities. We will ask you questions about yourself including your 
medical and sexual history, and some blood samples will be collected. Should you be 
eligible and agree to participate, we will collect additional samples including blood, hair 
and fluids from your genital area. 
• 
Risks. Most studies have some possible harms that could happen to you if you join.  In 
this study, we expect that the primary risks will be some discomfort from sample 
collection, stress or discomfort from answering survey questions. 
• 
Benefits. We expect some benefits from this study, as well.  For you, we don’t think that 
you may get direct benefit from being in this study. However, we will inform you about any 
test results that are done that could be useful to your health care. 

 
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• 
Alternatives. Participation is voluntary and the only alternative is to not participate. 
 
INFORMED CONSENT  
We are asking you to volunteer to have screening tests to find out if you are eligible for a research 
study.  This study is open to women who do not have HIV. Before you decide whether to take part 
in the study, we would like to explain the purpose of the study, the risks and benefits, and what 
would be expected of you if you agree to be in the study. This study is being coordinated through 
the Kenya Medical Research Institute in Kenya and the University of Washington located in 
Seattle, Washington, USA. The study is being funded through the pharmaceutical company, 
Gilead Sciences, which makes Descovy®TM.  If you decide to participate in the research study, 
you will be asked to sign this consent form or make your mark in front of a witness. We will give 
you a copy of this form if you choose to have. This consent form might contain some words that 
are unfamiliar to you. Please ask us to explain anything you may not understand. 
 
PURPOSE OF THE STUDY  
Medication called Tenofovir /Emtricitabine (Truvada) can lower the chances for HIV-uninfected 
men and women to get the HIV virus. This is called preexposure prophylaxis or PrEP. Truvada 
PrEP is approved by the World Health Organization and the Kenya ministry of Health as one 
option to prevent getting HIV. A similar medication called Tenofovir alafenamide /Emtricitabine 
(Descovy®) has also been shown to work as well as Truvada PrEP to lower the chances of getting 
HIV in men . Research studies are ongoing to understand how Descovy® PrEP works in women 
in Africa. Other research studies have shown that the levels of drugs in blood after taking PrEP 
may be different in men and women. The purpose of this study is to find out more about the levels 
of TAF PrEP in blood and other body samples when used by women. 
 
YOUR PARTICIPATION IS VOLUNTARY  
This consent form gives information about the study that we will discuss with you. Before you 
learn about the study procedures, it is important that you know the following:  
• 
You do not have to be in this study if you do not want to join.  
• 
You may decide not to take part in the study, or to withdraw from the study at any time.  
• 
If you decide not to take part in the study, you can still join another research study later, if one 
is available and you qualify.  
 
SCREENING PROCEDURES  
Screening procedures will begin today, after you read, discuss, and sign or make your mark on 
this form. The screening procedures will include the following:  
• 
The study staff will check your temperature and ask you questions about COVID-19 
symptoms and people you been in physical contact with, to see if you have been exposed to 
COVID-19. Should the staff determine that you have been exposed, they will follow the 
recommended Ministry of Health guidelines in referring you for healthcare. We will 
reschedule your visit for another time based on these guidelines.  
• 
The study staff will ask you where you live and other questions about your sexual practices, 
medical history and, pregnancy and contraceptive use intentions.  
• 
A clinician will perform a physical exam, urine pregnancy test and review your medication 
and COVID-19 vaccination status. 

 
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• 
We will counsel you about HIV and other infections passed during sex, and how to avoid 
these infections.  
• 
Even if you have recently been tested for HIV, we will need to repeat the HIV test today as 
part of screening for the study. The study staff will talk with you about the HIV test, what it 
may mean to know your HIV test results. You must receive your HIV test results to be in the 
research study.  
• 
If you do not have HIV infection:  
§ 
We will ask you questions about your medical and sexual health history, and pregnancy 
intentions.  
§ 
You will be asked to give us permission to obtain a blood sample for laboratory tests. No 
more than 21 ml (about one and quarter tablespoons) will be collected for all the 
screening tests, including the HIV test.  Some of the blood sample will be used to test for 
hepatitis B infection and some will be used to test the function of your kidneys.  
The study staff will fully explain the study to you and answer any questions you have. You must 
have at least one other visit here at the clinic to learn about the study. If you decide to take part 
in the research study and found to meet all the requirements for the study, you will be asked to 
sign another consent form at another visit. 
 
RISKS AND/OR DISCOMFORTS  
You may feel discomfort or pain when your blood is drawn. You may feel dizzy or faint. You may 
have a bruise where the sterile instrument (needle) goes into your arm. On rare occasions, 
infection may occur at the site of blood draw or fingerstick. All efforts will be made to ensure this 
doesn’t happen by using standard clean and sterile procedures for drawing blood. In the unlikely 
event that the infection occurs at the site of blood draw, trained clinicians will help you get the 
necessary treatment or refer you the appropriate health facility, at no cost to you. 
You may become embarrassed, worried, or anxious when talking about your sexual practices, 
ways to protect against HIV and other infections passed during sex, and your test results. You 
may become worried or anxious while waiting for your test results. Having the screening tests, 
talking about HIV, and finding out your results could cause problems between you and your 
partner. The counseling that you will receive through the study staff will help you understand the 
results. Trained counselors are available through the study who will help you deal with any 
feelings or questions you may have.  
The study staff will make every effort to protect your privacy and confidentiality while you are 
having the screening tests. However, it is possible that others may learn of your participation here 
and, because of this, may treat you unfairly or discriminate against you. For example, you could 
have problems getting or keeping a job, or being accepted by your family or community. 
 
BENEFITS  
You may get no direct benefit from the screening tests. However, you will get counseling and 
testing for HIV. You will get information on how to protect against HIV and other infections passed 
during sex. You will get free condoms. For other health problems that cannot be treated at this 
clinic, the study staff will tell you about other places you can go for treatment. The study staff will 
also tell you about other places that provide HIV prevention and care services. You may also 
contribute to understanding HIV prevention in women in Africa, which will help others in the future. 
 
COSTS TO YOU  
There is no cost to you for being in this study. Treatments available to you by the study will be 

 
Women TAF-FTC Benchmark Study   
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free of charge.  
 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE STUDY  
You may be removed from the study without your consent for the following reasons:  
• 
The research study is stopped or canceled.  
• 
You are not willing to find out your HIV test result.  
• 
You are put in prison 
• 
You are not able to attend clinic visits or complete the screening tests.  
• 
The researchers may determine that this study may not be a good fit for you  
• 
The study staff feels that having the screening tests would be harmful to you.  
 
ALTERNATIVES TO PARTICIPATION  
There may be other studies going on here or in the community that you or your partner may be 
eligible for. You may also be able to access PrEP through other research studies going on here 
or in other clinics in the community. If you wish, the study staff will tell you about other studies or 
healthcare facilities which offer PrEP that we know about. There also may be other places you 
can go for HIV counseling and testing. We will tell you about those places if you wish. 
 
REIMBURSEMENT  
You will receive reimbursement for your transport for visiting the clinic, and 400 KSh for your time 
and effort at each scheduled study screening visit.  
 
CONFIDENTIALITY  
All study staff will make every effort to protect the privacy of your personal information but cannot 
completely guarantee this. Any sample from you or information about you will be identified only 
by code and not by name.  The link between your name and code will be kept in a secure location 
at the clinic only. The U.S. Food and Drug Administration (FDA) reserves the right to review study 
data that may contain identifying information. Any publication of this study will not use your name 
or identify you personally.   Certain people and organizations will need to see, copy, and use your 
health data so that they can do their part in the study. They are called ‘authorized users’. The 
records of your tests may be reviewed by study staff and representatives of the following 
authorized users: 
• 
Kenya Medical Research Institute (KEMRI) Scientific and Ethics Review Unit (SERU) 
• 
Kenya Pharmacy and Poisons Board 
• 
University of Washington, including study monitors 
• 
Gilead Sciences 
• 
Kenya Ministry of Health  
• 
University of Colorado 
• 
Other local, U.S. and international regulatory entities  
The review of records may be done on-site or remotely through secured authorized computer 
programs. Remote monitoring visits may be performed in place of, or in addition to onsite visits to 
ensure the safety of study participants and data integrity.  
 
FUTURE USE OF DATA 
The information that we obtain from you for this study might be used for future studies. We may 
remove anything that might identify you from the information. If we do so, that information may 

 
Women TAF-FTC Benchmark Study   
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then be used for future research studies or given to another investigator without getting additional 
permission from you. It is also possible that in the future we may want to use or share study 
information that might identify you. If we do, the Scientific and Ethics Review Unit (SERU) and 
the researchers’ appropriate ethical committee or institutional review board will decide whether or 
not we need to get additional permission from you. 
 
RETURN OF RESEARCH RESULTS 
You will be made aware of the results of rapid HIV, hepatitis B, creatinine, blood count, and urine 
pregnancy tests done as part of screening procedures for research study. If any results are 
abnormality and you will be referred to health facility where can get it the treatment or to a health 
facility of your choice.  
 
RESEARCH-RELATED INJURY  
We do not anticipate any research related injury. However, if you feel you are injured from 
participating in this study, you will be offered care at the study clinic, free of charge. For research 
related injury, please call the 24-hour emergency number: 0736464299.There is not a program of 
monetary compensation through this institution. If you need medical care that we cannot provide, 
we will refer you to the appropriate services or organizations that can provide care for the injury. 
You do not give up any legal rights by signing this consent form. You do not waive any right to 
seek payment or give up any legal rights by signing this consent form. 
PROBLEMS OR QUESTIONS  
If you ever have any questions about this study, or if you have a research-related injury, you 
should contact Catherine Kiptinness at the Thika Partners in Prevention Study clinic at Tel. 067 
2222561/0725 641110.  For research related injury, please call the 24-hour emergency number: 
0736464299.  If you have questions about your rights as a research participant, you should 
contact: The Head, Scientific and Ethics Review Unit (SERU) Kenya Medical Research Institute 
(KEMRI), P.O Box 54840-00202 Nairobi Phone No. 0717719477, Email address: 
seru@kemri.org. A description of this study will also be available on https://www.clinicaltrials.gov 
as required by U.S. Law. This Web site will not include information that can identify you. At most, 
the Web site will include a summary of the results. You can search this Web site at any time. 
 
STATEMENT OF CONSENT AND SIGNATURES  
I have read the study enrollment consent for this study, or had it read to me. I have discussed the 
information with study staff. My questions have been answered. I understand that my decision 
whether or not to take part in the study is voluntary. I understand that if I decide to join the study 
I may withdraw at any time. By signing this form, I do not give up any rights that I have as a 
research participant.  
 
____________________  
_________________________  
______________  
Participant Name  
 
Participant Signature/Thumbprint  
Date  
(print)  
_____________  
________________________  
_____________  
Study Staff Name 
 
Staff Signature  
 
 
Date  
 
 

 
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____________________ 
________________________            ______________ 
Witness Name 
 
 
Witness Signature 
 
 
   Date 
(print) 
Participating in future research studies  
We would like to contact you in the future to see if you would be interested in participating in future 
studies. Please indicate below if you are willing to be contacted about any future research studies.  
 
Yes: I agree to be contacted about future research studies  
 
 
No: I do not want to be contacted about future research studies 
 
____________________  
_________________________  
______________  
Participant Name (print)  
Participant Signature/Thumbprint  
Date  
 
____________________  
________________________  
_____________  
Study Staff Name 
 
Staff Signature  
 
 
Date  
 
____________________ 
________________________            ______________ 
Witness Name (print) 
 
Witness Signature 
 
 
   Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Women TAF-FTC Benchmark Study   
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Study Title: Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan 
Cisgender women 
Study Enrollment Informed Consent Form 
Version 1.1, August 15, 2022 
 
INVESTIGATORS 
Investigator 
Title 
Institution 
Telephone  
Kenneth Mugwanya 
MBChB, MS, PhD 
University of Washington 
001 206-520-3886 
Nelly Mugo 
MBChB, M.Med, MPH 
Kenya Medical Research Institute 067 2222561 
Peter Anderson 
PharmD 
University of Colorado 
001 303-724-6128 
Elizabeth Irungu 
MBChB, MPH, PhD 
Kenya Medical Research Institute  067 2222561 
Catherine Kiptinness B. Pharm, MPH 
Kenya Medical Research Institute  067 2222561 
 
STUDY LOCATION: The study will be conducted at Thika.  
You are being asked to take part in a research study. The box below tells you important things 
you should think about before deciding to join the study.  We will provide more detailed information 
below the box. Please ask questions about any of the information before you decide whether to 
participate. You may also wish to talk to others (for example, your family, friends, or your doctor) 
about this study, before agreeing to join.    
Key Information for You to Consider 
• 
Voluntary Consent. You are being asked to volunteer for a research study.  It is up to 
you whether you choose to participate or not.  There are no penalties and you will not 
lose anything if you decide not to joint or if after you join, you decide to quit.  
• 
Purpose. We are doing this research to find out more about the medication called 
Tenofovir alafenamide /Emtricitabine (TAF/FTC or Descovy®). Descovy® has been 
shown to lower the chances of getting HIV  in HIV-uninfected men . This is also called 
preexposure prophylaxis or PrEP. Research studies are now ongoing to understand how 
Descovy® PrEP works to prevent HIV in women. We want to learn more about the levels 
of PrEP medication in blood and other body parts when used by women. 
• 
Duration. Your part of the study will last for about up to 4 ½ months; up to 2 ½ months 
when taking medication and 2 months after you stop. 
• 
Procedures and Activities. We will ask you questions about yourself including your 
medical and sexual history. At study specified visits you will take a tablet of PrEP in the 
presence of study staff and study specified samples including hair, blood, tissue and 
fluids from your genital area will be collected. 
• 
Risks. Most studies have some possible harms that could happen to you if you join.  In 
this study, we expect that the primary risks will be some pain and discomfort from sample 
collection, stress or discomfort from answering survey questions, and breach in 
confidentiality  
• 
Benefits. We expect some benefits from this study, as well.  For you, we don’t think that 
you may get direct benefit from being in this study. However, we will inform you about 
any test results that are done that could be useful to your health care. 
• 
Alternatives. Participation is voluntary and the only alternative is to not participate. 
 

 
Women TAF-FTC Benchmark Study   
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Page 61 of 69 
 
 
INFORMED CONSENT  
We are asking you to volunteer for a research study about medication used to prevent HIV. This 
study is open to women who do not have HIV and are not pregnant. Before you decide whether 
to take part in the study, we would like to explain the purpose of the study, the risks and benefits, 
and what would be expected of you if you agree to be in the study. This study is being coordinated 
through the Kenya Medical Research Institute in Kenya and the University of Washington located 
in Seattle, Washington, USA. The study is being funded through the US drug company Gilead 
Sciences, which makes Descovy®. If you decide to participate in the research study, you will be 
asked to sign this consent form or make your mark in front of a witness. We will give you a copy 
of this form if you choose to have. This consent form might contain some words that are unfamiliar 
to you. Please ask us to explain anything you may not understand.  
 
PURPOSE OF THE STUDY  
Medication called Tenofovir /Emtricitabine (Truvada) can lower the chances for HIV-uninfected 
men and women to get the HIV virus. This is called preexposure prophylaxis or PrEP. Truvada 
PrEP is approved by the World Health Organization and the Kenya ministry of Health as one 
option to prevent getting HIV. A similar medication called Tenofovir alafenamide /Emtricitabine 
(Descovy®) has also been shown to lower the chances of getting HIV in men. Research studies 
are now ongoing to understand how Descovy® PrEP works to prevent HIV in women. Research 
studies have also shown that PrEP works only when taken as prescribed. Other research studies 
have shown that the levels of drugs in blood after taking PrEP may be different in men and women. 
The purpose of this study is to find out more about the levels of TAF PrEP in blood and other body 
samples when used by women. The results of this study will help to understand how Descovy® 
works in women when used as PrEP to prevent getting HIV. Overall, approximately 54 women, 
all from Kenya, will be in the study. The samples and data that we collect in this study may help 
us learn more how these medications work to prevent HIV infection in women. All participants 
who agree to be in this study will be asked to provide data and samples for up to 18 weeks.  
 
YOUR PARTICIPATION IS VOLUNTARY  
This consent form gives information about the study that we will discuss with you. Before you 
learn about the study procedures, it is important that you know the following:  
• 
You do not have to be in this study if you do not want to join.  
• 
You may decide not to take part in the study, or to withdraw from the study at any time.  
• 
If you decide not to take part in the study, you can still join another research study later, if one 
is available and you qualify.  
 
 
STUDY PROCEDURES 
If you decide to join the study, you will have study visits up to 18 weeks. At these visits, the study 
staff will confirm where you live and other questions about your sexual practices, medical history 
and, pregnancy and birth control use intentions. A clinician will also review your medication and 
vaccine history. If you are eligible to participate in the study, then the study team will randomly 
assign you by chance (like flipping a coin) to one of three study groups. The staff do not know 
ahead of time which group you will fall into.  

 
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At each clinic visit, the study staff will check your temperature and ask you questions about 
COVID-19 symptoms and people you been in physical contact with, to see if you have been 
exposed to COVID-19. Should the staff determine that you have been exposed, they will follow 
the recommended Ministry of Health guidelines in referring you for healthcare. We will reschedule 
your visit for another time based on these guidelines.  
At study specified visits you will take a tablet of PrEP in the presence of study staff and study 
specified samples will be collected. 
At enrollment you:  
• 
Will be told the number of visits and numbers of doses of PrEP you will take every week. 
There are three groups of dosing of PrEP you may be assigned to. You may either be in 
a group that will take two doses every week or four doses in a week or seven doses 
every week. Only chance will determine which group you will be in. 
• 
If you are assigned to two (2) doses every week, you will come to the clinic to take your 
medication on Mondays and Tuesdays. 
• 
If you are assigned to four (4) doses every week, you will be asked to come to the clinic 
to take your medication on Mondays, Tuesdays, Thursdays, and Fridays of every week. 
• 
If you are assigned to seven (7) doses every week, you will come to the clinic every day 
of the week Monday to Sunday to take your medication. 
• 
Will be given a study follow-up calendar to help you remember study visits. 
• 
Will be provided with a month supply (a bottle) of back-up medication to be used if you are 
unable to complete the visit in person at the clinic. 
 
At enrollment and each study visit you:  
• 
Will be given PrEP tablet medication to take in their presence (called directly observed 
therapy) at the clinic. All doses taken away from the clinic will still be directly observed by 
study staff via live video streaming on a smart cell phone or computer via WhatsApp. For 
doses taken via video streaming, you will be asked to open your mouth afterwards to 
confirm swallowing. You will be supported with reasonable internet bundles consistent 
with the SERU recommendation. 
• 
Will be counseled about possible drug side effects. 
• 
Will be asked questions about your health and medical history, sexual behaviors, and your 
feelings about taking medication for HIV prevention.  
• 
Will talk with study staff about ways to avoid HIV and other infections passed during sex. 
You will be offered condoms.  
• 
Will get medical care or referrals for medical care and other services if you need them. 
• 
Will be asked to give updated information on where you live and how to keep in contact 
with you. The study staff will use this information to remind you of scheduled visits. If you 
don’t return to the clinic on schedule, the study staff may try to contact you by phone or 
by visiting your home. They may try to reach you through the contact people that you list. 
If they talk to these people, they will not tell them why they are trying to reach you. If a 
home visit is done, study staff may ask you take study drug in their presence or provide 
some scheduled study samples. 
• 
Obtain blood samples [up to 21 mL / about one and quarter tablespoon] at each of these 
visits. 
• 
Provide a urine sample in a container [up to 10 mL / a little more than half tablespoon] at 
each of these visits 
 

 
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At enrollment, day 4, week 1, and then weekly up to week 10 visits: 
We will ask your permission to obtain study samples at these visits. Study samples may include 
blood, urine, hair, and vaginal tissue. The samples will be used by study researchers for tests to 
determine the amount of study drugs in the samples. We will ask for your permission to: 
• 
Obtain hair samples at week 4 and week 8. The hair sample will be about 50-100 
strands (which is what we need for this test) and is less than you naturally lose from your 
head each day. We will test for PrEP drug levels in the hair sample at the end of the 
study. Your hair will not be stored in any way but destroyed after testing for the PrEP 
drug levels 
• 
Obtain vaginal swab and biopsy at day 4, week 1, week 4 and week 8. Women who 
provide vaginal biopsy at day 4 will not have another biopsy at week 1 but will provide 
the remaining samples at week 4 and week 8. When you provide a vaginal biopsy, 
you must abstain from sex for at least seven days. 
• 
Obtain a blood sample by finger prick [ week 1 (days 4 and 7), week 4 and week 8].  
• 
Provide urine for a pregnancy test at entry, week 4 and week 8 visits. If you become 
pregnant, you will stop taking the study drug and we will continue to follow you till the 
end of your pregnancy. 
• 
Conduct HIV-1 rapid test at week 4 and week 8 visits.  
• 
If you become infected with HIV, you will stop taking the study drug and we will then 
refer you to a nearby HIV care services or at a clinic of your choice for follow up at 
completion of this trial. 
• 
If you withdraw or are withdrawn before the end of the study, we may ask you to 
complete a separate early exit visit, so that we can check you, to make sure you are 
healthy before your exit. 
 
After 10 weeks of taking PrEP medication: 
We will ask you to come in for two additional visits, where we will ask for your permission to obtain 
the following study samples: 
• 
Blood samples [up to 21 mL / about one and quarter tablespoon] at each of these visits. 
• 
Urine sample in a container [up to 10 mL / a little more than half tablespoon] at each of 
these visits 
 
BIOMETRIC FINGERPRINT SCAN  
To help us keep track of who is enrolled in our clinic, and who is coming for follow up visits, we 
will ask you to put either your right or left index finger on a small machine that will scan your 
fingerprint. This scan will be linked to a unique identification number and will be accessible only 
to study staff. We will take your fingerprint at each study visit. You are free to refuse to have your 
fingerprint taken and this will not affect your participation in the study. The fingerprint database 
will be destroyed after completion of active follow up in the study.  
 
SPECIMEN STORAGE AND USE OF SAMPLES AND DATA FOR FUTURE STUDIES. We 
would like to save data from this study and samples of your blood, urine, tissue, and hair at the 
Thika clinic and the University of Washington for future research by us and by other researchers. 
Some samples will be shipped to our laboratories in Mombasa and Nairobi, Kenya for testing. For 
specialized tests that cannot be done in Kenya, your samples will be shipped to the University of 

 
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Washington, Ninth and Jefferson Building, 908 Jefferson Street, Seattle, WA 98104 and the 
Galloway Lab, FHCRC, 1100 Fairview Avenue N., C1-015, Seattle, WA  98109 and University of 
Colorado in the USA. You will not receive any results that come from samples that are tested 
in the USA.  We will use these samples only for research related to HIV, sexually transmitted 
infections and reproductive health.  This will include studies on HIV and STI prevention, how 
people respond to the medications used in this study or how the drugs interact with contraception, 
organism in genital areas or studies of variation in gene DNA of drug transporter. Gene studies 
will only be for studies related to proteins which transport drugs in the body (drug transporters) 
not for full genome wide sequencing.  
This research is experimental, and these tests are not useful for your clinical care. Before your 
samples leave the clinic, they will be assigned a code and your name will not be on them. Your 
name will be linked to the code only at this clinic. If you do not want to have your samples saved 
for future research, you can still be in this study and your samples will be destroyed once testing 
for this study is completed. If you agree to store your samples now, but change your mind before 
the study ends, let the study staff know and we will make sure your samples do not get stored for 
future research. There will be no consequences for changing your mind. However, after the link 
between your samples and your name is destroyed, we will not be able to identify your samples. 
We will not sell your data or samples. Tests done on your samples may lead to a new invention 
or discovery. We have no plans to share money or other benefits resulting from such invention or 
discovery with you. 
 
FUTURE USE OF DATA AND SAMPLES 
The information and/or specimens that we obtain from you for this study might be used for future 
studies. We may remove anything that might identify you from the information and specimens. If 
we do so, that information and specimens may then be used for future research studies or given 
to another investigator without getting additional permission from you. It is also possible that in 
the future we may want to use or share study information that might identify you. If we do, SERU 
and the researchers’ appropriate ethical committee or institutional review board will decide 
whether or not we need to get additional permission from you. 
 
RETURN OF RESEARCH RESULTS 
You will be made aware of the results of rapid HIV, hepatitis B, creatinine, blood count, and urine 
pregnancy tests done as part of research. Trained research staff will share the results with you in 
person during visits or through a phone call. You will also be made aware of results from batched 
baseline STI testing. If any results are abnormal, you will receive standard of care treatment here 
at the clinic in a timely manner. For treatment not available at the clinic, you will be referred to 
clinics where you can get it. Testing on blood drug levels or future studies will not be shared with 
you. This research is experimental, and these tests are not useful for your clinical care. 
 
RISKS 
You may become embarrassed, worried, or anxious when talking about your sexual practices, 
ways to protect against HIV and other infections passed during sex. If you are not now infected 
with HIV but become infected with HIV, this could make you worried or anxious. Talking about 
HIV and finding out your test results could cause problems between you and your partner. Trained 
counselors will help you and your partner deal with any feelings or questions you may have about 

 
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these issues. If your partner finds out that you are on PrEP, this may lead to disagreements or 
physical/verbal abuse. It may also lead to economic risks such as loss of income or financial 
support. We anticipate that these risks will be rare. If threats of violence arise, avoid confrontation 
and consider seeking help from family, friends, your other social networks or study staff. 
 
The study staff will make every effort to protect your privacy and confidentiality while you are 
having the study procedures. However, it is possible that others may learn of your participation 
here and, because of this, may treat you unfairly or discriminate against you. For example, you 
could have problems getting or keeping a job, or being accepted by your family or community.  
Risks related to collection of study samples: This study requires the use of your blood. There 
will be some pain associated with the needle stick, but this will be only for a short period of time. 
There may be some bruising around the needle site and, although we will sterilize the site to 
minimize infection, there is a very minimal risk of infection at the site. You may feel discomfort or 
pain when your blood is drawn. You may feel dizzy or faint. You may also have slight discomfort 
or pain during the prick of your finger, and there is a small risk of infection, bleeding or bruising 
from the fingerstick.  
 
Some people may be embarrassed about providing urine, hair, and tissue samples. There is also 
some discomfort associated with taking hair or biopsy specimens. The biopsy may feel like a 
pinch each time a sample is taken and may cause some cramping with it. Any pain or cramping 
occurring during the biopsy may be helped by relaxing and taking a few slow deep breaths. Some 
vaginal bleeding and a small amount of dark brown discharge are normal after the sampling. 
Abstaining from sex for at least 7 days after the biopsy, and taking the HIV-prevention drug, 
TAF/FTC, will help reduce your risk of HIV infection after having biopsies collected. If you 
become pregnant during the study, you will not have a vaginal biopsy.  We will still perform 
vaginal swab, secretion collection, which are not a risk for the pregnancy.  
 
Risks potentially related to the TAF/FTC PrEP medication: TAF/FTC PrEP medication is 
similar to TDF/FTC PrEP which is approved for PrEP in Kenya. You may have symptoms or 
adverse effects while participating in the study. The adverse effects that can occur in a small 
proportion of people taking PrEP are well known because the medication has been used by many 
people. These adverse effects are similar to those seen with TDF/FTC PrEP but studies have 
also shown that they may be even fewer in TAF/FTC. TAF/FTC PrEP medication is very safe but 
like any medication, some mild adverse effects are expected to occur in up to 1 in 10 persons 
who take TAF/FTC. These include headache, stomach upset, vomiting or loss of appetite. 
Occasional adverse effects may include mild problems of kidney function that are only detected 
by laboratory tests. Small changes in the mineral density of bones were observed in studies of 
people who were given TAF/FTC PrEP, but the changes in the mineral density of the bones did 
not cause any fractures, or other problems that bothered the patients. Other potential serious but 
rare risks of PrEP include kidney failures such as Fanconi’s syndrome and hypersensitivity 
reactions.  
 
Other adverse effects which have been seen persons who have advance HIV infection and have 
used TAF/FTC together with other drugs for treatment include:  
• 
Increase in body fat around the waist and stomach area, and back of the neck 

 
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• 
Thinning of the face, legs and arms 
• 
Breast enlargement 
• 
Gas, loose or watery stools 
• 
Generalized weakness 
• 
Dizziness 
• 
Depression 
• 
Rash 
• 
Allergic reaction: symptoms may include fever, rash, upset stomach, vomiting, loose or 
watery stools, abdominal pain, achiness, shortness of breath, a general feeling of illness 
or a potentially serious swelling of the face, lips, and/or tongue 
• 
Muscle pain and muscle weakness 
• 
Sleeping problems  
• 
Lactic acidosis has occurred in some HIV-infected persons taking PrEP, in combination 
with other drugs. Lactic acidosis is a condition that can produce shortness of breath, 
nausea, and liver failure. This is a serious adverse effect of some medications used for 
HIV infection. Hypersensitivity reactions 
• 
serious but rare risks of kidney failures such as Fanconi’s syndrome .  
These adverse events are very rare and unlikely to occur in HIV uninfected persons use FTC/TAF 
PrEP. If you have these symptoms, or any other symptoms that concern you, the study 
staff will evaluate your symptoms and determine whether you should stop your PrEP pills. 
You will be given a telephone number where the study doctors will be available 24 hours a day, 
7 days a week.  
Risk of acquiring HIV infection:  
Only daily TDF/FTC PrEP is recommended for use to prevent HIV in men and women in Kenya. 
Descovy® PrEP is not yet approved for use to prevent HIV in women. In this study you may 
receive non-daily dosing of Descovy® PrEP which doesn’t provide sufficient protection. You may 
be exposed to get HIV from sexual partners you may have. It is very important to use all the known 
strategies to prevent getting HIV, like using condoms for all sexual relations and keeping your 
number of sexual partners low. Each visit you will get risk-reduction counseling for ways to protect 
yourself. You will have an HIV test every 4 weeks. If we find that you have HIV, PrEP will be 
immediately discontinued. You will be started on free HIV treatment immediately as per the Kenya 
national guidelines and we will then refer you to a nearby HIV care services or at a clinic of your 
choice for follow up at completion of this trial.  
 
New findings 
We will provide you with any new information that we learn during the study, which might affect 
your willingness to participate. 
 
BENEFITS 
You may get no direct benefit from being in this study. We will inform you about any test results 
that are done that could be useful your health care. You or others may benefit in the future from 
information learned in this study. You also may get some personal satisfaction from being part of 
research on HIV. While enrolled in the study you will get all services available to those not in the 
study such as access to oral PrEP (which is known to help prevent HIV infection), counseling for 
reducing your risk of giving HIV to or getting HIV from your sexual partner, and free condoms. For 

 
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care and treatment that is not available at the clinic, study staff will tell you about other places 
where care and treatment may be available. Your participation may also contribute to 
understanding about HIV prevention in women in Africa, which will help others in the future. 
 
COSTS TO YOU  
There is no cost to you for being in this study. Treatments available to you by the study will be 
free of charge.  
 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE STUDY  
You may be removed from the study without your consent for the following reasons:  
• 
The study is stopped or canceled.  
• 
You are put in prison. 
• 
Your intentions about pregnancy and birth control use change. 
• 
The study staff feel that staying in the study would be harmful to you.  
• 
You are not able to attend study visits or complete the study procedures. 
 
ALTERNATIVES TO PARTICIPATION  
There may be other studies going on here or in the community that you or your partner may be 
eligible for. You may also be able to access PrEP through other research studies going on here 
or in other clinics in the community. If you wish, the study staff will tell you about other studies or 
healthcare facilities which offer PrEP that we know about. There also may be other places you 
can go for HIV counseling and testing. We will tell you about those places if you wish. 
 
REIMBURSEMENT  
You will receive reimbursement for your transport for visiting the clinic, and 400 KSh for your time 
and effort at each scheduled study visit. All visits that include collection of biopsies will be 
reimbursed 2000 KSh. All visits that include collection of vaginal swabs alone will be reimbursed 
1000 KSh. 
 
CONFIDENTIALITY  
Government or university staff sometimes review studies such as this one to make sure they are 
being done safely and legally. If a review of this study takes place, your records may be examined.  
The reviewers will protect your privacy.  The study records will not be used to put you at risk of 
legal harm. All study staff will make every effort to protect the privacy of your personal information 
but cannot completely guarantee this. Any sample from you or information about you will be 
identified only by code and not by name. The link between your name and code will be kept in a 
secure location at the clinic only. The U.S. Food and Drug Administration (FDA) reserves the right 
to review study data that may contain identifying information. Any publication of this study will not 
use your name or identify you personally.   Certain people and organizations will need to see, 
copy, and use your health data so that they can do their part in the study. They are called 
‘authorized users’. The records of your tests may be reviewed by study staff and representatives 
of the following authorized users: 

 
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• 
Kenya Medical Research Institute (KEMRI) Scientific and Ethics Review Unit (SERU) 
• 
Kenya Pharmacy and Poisons Board 
• 
University of Washington, including study monitors 
• 
Gilead Sciences 
• 
Kenya Ministry of Health  
• 
University of Colorado 
• 
Other local, U.S. and international regulatory entities  
 
The review of records may be done on-site or remotely through secured authorized computer 
programs. Remote monitoring visits may be performed in place of, or in addition to onsite visits to 
ensure the safety of study participants and data integrity.  
 
RESEARCH-RELATED INJURY  
We do not anticipate any research related injury. However, if you feel you are injured from 
participating in this study, you will be offered care at the study clinic, free of charge. For research 
related injury, please call the 24-hour emergency number: 0736464299.There is not a program of 
monetary compensation through this institution. If you need medical care that we cannot provide, 
we will refer you to the appropriate services or organizations that can provide care for the injury. 
You do not give up any legal rights by signing this consent form. You do not waive any right to 
seek payment or give up any legal rights by signing this consent form. 
 
PROBLEMS OR QUESTIONS  
If you ever have any questions about this study, or if you have a research-related injury, you 
should contact Catherine Kiptiness at the Thika Partners in Prevention Study clinic at Tel. 067 
2222561/0725 641110.  For research related injury, please call the 24-hour emergency number: 
0736464299.  If you have questions about your rights as a research participant, you should 
contact: The Head, Scientific and Ethics Review Unit (SERU) Kenya Medical Research Institute 
(KEMRI), P.O Box 54840-00202 Nairobi Phone No. 0717719477, Email address: 
seru@kemri.org. A description of this study will also be available on https://www.clinicaltrials.gov. 
as required by U.S. Law. This Web site will not include information that can identify you. At most, 
the Web site will include a summary of the results. You can search this Web site at any time. 
 
STATEMENT OF CONSENT AND SIGNATURES  
I have read the study enrollment consent for this study, or had it read to me. I have discussed the 
information with study staff. My questions have been answered. I understand that my decision 
whether or not to take part in the study is voluntary. I understand that if I decide to join the study 
I may withdraw at any time. If I refuse to be in the study or decide to stop being in the study I will 
have no loss of benefits to which I am already entitled. By signing this form, I do not give up any 
rights that I have as a research participant.  
 
______________________ __________________________ 
 
________________ 
Participant Name (print) 
Participant Signature/Thumbprint 
 
Date 
 
____________________ 
__________________________ 
 
________________ 
Study Staff Name (print)  
Study Staff Signature  
 
 
Date 

 
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__________________ 
__________________________ 
 
________________ 
Witness Name (print)  
Witness Signature 
 
 
    
Date 
 
 
SPECIMEN SHIPMENT, STORAGE AND USE OF YOUR DATA AND SAMPLES FOR FUTURE 
STUDIES:  
Please initial and date one option: 
 
___________ I agree for my specimen to be shipped, and for my specimen/information to be 
used for future research and shared with other researchers without my additional consent without 
identifiers 
 
___________ I DO NOT agree for my specimen to be shipped and for my specimen/information 
to be used for future research or shared with other researchers with or without identifiers 
 
 
STATEMENT OF CONSENT: BIOMETRIC FINGERPRINT 
Please initial and date one option:  
 
___________  I agree to have my fingerprint taken  
 
____________I DO NOT agree to have my fingerprint taken 
 
______________________ __________________________ 
 
________________ 
Participant Name (print) 
Participant Signature/Thumbprint 
 
Date 
 
____________________ 
__________________________ 
 
________________ 
Study Staff Name (print)  
Study Staff Signature  
 
 
Date 
 
__________________ 
__________________________ 
 
________________ 
Witness Name (print)  
Witness Signature 
 
 
    
Date 
 
RECEIVING OFF-SITE VISITS, PLEASE TICK YOUR CHOICE BELOW 
We would like to conduct your study visits at home or at a mutually agreed location, to make the 
visits more convenient for you. 
  
             I DO agree to arranging study visits at a mutually agreed location. 
 
  
             I DO NOT want to have visits at other locations other than the clinic. 
 
Copies to; 
1. 
Investigators 
2. 
Study participant