Weekly Doxycycline DOT for STI Prevention Among Cisgender Women Taking HIV PrEP in Kisumu, Kenya
Phase: PHASE4
Conditions: STI
Sponsor: University of Washington

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PROTOCOL 
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Weekly doxycycline DOT for STI prevention among cisgender women taking HIV PrEP in Kisumu, Kenya 
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Funded by: US National Institutes of Health 
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Version 1.1 
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May 15, 2024 
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Table of Contents 
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STUDY TEAM ...................................................................................................................................................... 3 
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GLOSSARY........................................................................................................................................................... 4 
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ABSTRACT ........................................................................................................................................................... 5 
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LAY SUMMARY .................................................................................................................................................. 6 
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1. 
BACKGROUND AND SIGNIFICANCE ............................................................................................. 7 
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1.1. 
Background ............................................................................................................................................. 7 
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1.2. 
Rationale .................................................................................................................................................. 8 
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2. 
OBJECTIVES ....................................................................................................................................... 10 
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2.1. 
Primary Study Objectives: .................................................................................................................. 10 
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2.2. 
Secondary Study Objectives: ............................................................................................................... 10 
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3. 
METHODOLOGY ............................................................................................................................... 10 
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3.1. 
Design ..................................................................................................................................................... 10 
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3.2. 
Selection and enrollment of participants ............................................................................................ 10 
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3.3. 
Study treatment .................................................................................................................................... 11 
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3.4. 
Study procedures .................................................................................................................................. 12 
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3.5. 
Study visits ............................................................................................................................................ 13 
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3.6. 
Adverse Events (AE) And Study Monitoring .................................................................................... 16 
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3.6.1. 
Adverse Event Collection Requirements ...................................................................................... 16 
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3.6.2. 
Study Monitoring .......................................................................................................................... 16 
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3.7. 
Medical Monitoring Committee .......................................................................................................... 16 
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3.8. 
Criteria for discontinuation ................................................................................................................. 17 
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3.8.1. 
Premature Study Treatment Discontinuation ................................................................................ 17 
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3.8.2. 
Premature Study Discontinuation ................................................................................................. 17 
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3.9. 
Statistical Considerations .................................................................................................................... 17 
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3.9.1. 
Outcome measures ........................................................................................................................ 17 
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3.9.2. 
Statistical power and analysis ....................................................................................................... 17 
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3.10. Biohazard Containment ....................................................................................................................... 18 
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4. 
ETHICAL CONSIDERATION .......................................................................................................... 18 
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4.1. 
Institutional Review Board (IRB) Review .......................................................................................... 18 
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4.2. 
Informed Consent ................................................................................................................................. 18 
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4.3. 
Study records ........................................................................................................................................ 18 
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4.4. 
Confidentiality ...................................................................................................................................... 19 
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4.5. 
Participants’ rights under data protection laws ................................................................................ 19 
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4.6. 
Risks/Benefits ........................................................................................................................................ 19 
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4.7. 
Reimbursement ..................................................................................................................................... 20 
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4.8. 
COVID-19 safety measures ................................................................................................................. 20 
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4.9. 
Dissemination and utilization of study findings ................................................................................. 20 
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TIMELINE ............................................................................................................................................ 20 
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REFERENCES ..................................................................................................................................... 21 
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STUDY TEAM 
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Kenya Medical Research Institute, Kisumu, Kenya  
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Elizabeth A. Bukusi, MBChB, PhD, Co-Principal Investigator 
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Josephine Odoyo, KRCHN, MPH 
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Felix Ong’era Mogaka, MBChB, MPH 
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Victor Omollo, MBChB, MPH 
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Kevin Oware, MA 
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Hennepin Healthcare Research Institute, Minneapolis, MN 
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Jenell Stewart, DO, MPH, Project Director 
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Marya Abd El Hadi, BA 
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University of Washington, Seattle, WA 
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Jared M. Baeten, MD, PhD, Co-Principal Investigator 
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Olusegun O. Soge, MSc, PhD 
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Deborah Donnell, PhD 
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Lauren R. Violette, MPH 
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GLOSSARY  
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AE 
Adverse event 
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AMR 
antimicrobial resistance 
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ART 
Antiretroviral therapy  
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CDC 
Centers for Disease Control 
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COVID-19 
Coronavirus Disease 2019 
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CT 
Chlamydia trachomatis 
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DAIDS 
Division of AIDS 
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DALY 
Disability-adjusted life year 
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DOT 
Direct Observation Therapy 
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dPEP 
Doxycycline post-exposure prophylaxis 
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GEE 
Generalized estimating equations 
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HAL 
Hair Analytical Laboratory 
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HIV 
Human Immunodeficiency virus 
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HSV 
Herpes simplex virus 
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IATA 
International Air Transport Association 
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ICER 
Incremental cost effectiveness ratio 
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IDI 
In-depth interviews 
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IH 
Intracranial hypertension 
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IRB 
Institutional Review Board 
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IPV 
Intimate partner violence 
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KEMRI 
Kenya Medical Research Institute 
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LARC 
Long acting reversible contraceptives 
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LMP 
Last menstrual period 
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MOH 
Ministry of Health 
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MSM 
Men who have sex with men 
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NAAT 
Nucleic acid amplification test  
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NASCOP 
National AIDS & STI Control Programme 
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NG 
Neisseria gonorrhoeae 
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PCR 
Polymerase chain reaction 
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PEP 
Post-exposure prophylaxis 
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PID 
Pelvic inflammatory disease 
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PLWH 
People living with HIV  
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PPB ECCT 
Pharmacy and Poisions Board Expert Committee on Clinical Trials 
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PPE 
Personal protective equipment 
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PrEP 
Pre-exposure prophlaxis 
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RPR 
Rapid Plasma Reagin  
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SAE 
Serious Adverse Event 
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SMS 
Short message service 
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SOP 
Standard operating procedures 
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STIs 
Sexually transmitted infections 
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TDF/FTC 
Tenofovir/Emtricitabine 
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tetR 
Tetracycline resistant 
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UCSF 
University of California San Fransisco 
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UW 
University of Washington 
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VCT 
Voluntary counseling and testing 
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ABSTRACT 
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African women face disproportionate risk from overlapping epidemics of HIV and bacterial sexually transmitted 
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infections (STIs). HIV pre-exposure prophylaxis (PrEP) is emerging into a global context with unprecedented 
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rates of curable STIs. Post-exposure prophylaxis using the antibiotic doxycycline has been proposed as a novel 
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STI prevention strategy. The first study of doxycycline postexposure prophylaxis for cisgender women did not 
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reduce incident STIs likely due to low use of doxycycline. The overarching goal is to assess acceptability and 
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adherence to once-weekly doxycycline dosing to prevent STIs. We will conduct a pilot study of once-weekly 
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doxycycline to prevent bacterial STIs among Kenyan cisgender women using PrEP for HIV prevention. 
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Approximately 50 (up to 60) sexually active, cisgender women ages 18-30 years will be enrolled in this study 
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and followed for six months. Participants will receive doxycycline once-weekly dose as directly observed therapy 
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(DOT). All participants will complete STI testing (chlamydia, gonorrhea, and syphilis)at enrollment, month-three 
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and month-six. Prior to initiating treatment and at exit visit, all participants will have samples collected for future 
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microbiome and resistance testing. Hair samples will be collected at follow-up visits for future pharmacokinetic 
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model development. The primary endpoint is percentage of completed weekly DOT doxycycline doses. 
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Secondary endpoint is quarterly incident rate of Chlamydia trachomatis compared with quarterly incidence 
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among participants assigned to standard of care in the dPEP Kenya Study.  
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LAY SUMMARY 
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We propose to conduct research on weekly antibiotic, specifically doxyclycline, taken under the observation of 
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trained research staff, for prevention of bacterial sexually transmitted infections (STIs) among Kenyan women. 
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The study population will include up to sixty Kenyan women between 18 and 30 years old who are already using 
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a medication called pre-exposure prophylaxis (PrEP) for prevention of HIV. The study will be conducted at the 
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KEMRI-RCTP clinic at Lumumba Sub-County Hospital in Kisumu County, Kenya. The primary objectives of the 
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study are to assess the acceptability and continued use of weekly doxycycline when given under direct 
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observation. We will also measure rates of STIs when taking weekly doxycycline prophylaxis among HIV-
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uninfected Kenyan women compared with data from a similar population of participants in a recently completed 
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study (dPEP Kenya Study) in Kisumu, Kenya. Participants will be followed for six months. Participants will receive 
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doxycycline once-weekly dose with assistance from study staff to be taken under direct observation, and 
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participants will have STI (chlamydia, gonorrhea, and syphilis) testing and treatment at enrollment, at month-
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three, and at month-six. The primary outcome is continuation of antibiotic prophylaxis, or the percentage of 
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completed weekly doxycycline doses. Secondary outcomes include quarterly new infections with the bacterial 
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STI, Chlamydia trachomatis. Before starting study medicine and at the final visit, all participants will have samples 
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collected for future testing of bacteria that live in the reproductive and gastrointestinal tract and resistance to 
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antibiotics. Hair samples will be collected at follow-up visits for future study of the amount of doxycycline in hair 
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with once a week use of doxycycline. 
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1. BACKGROUND AND SIGNIFICANCE 
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1.1. 
Background 
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African women face disproportionate risk from overlapping epidemics of HIV and bacterial sexually 
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transmitted infections (STIs). More than two million persons become newly infected with HIV each year, the 
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majority in sub-Saharan Africa.1 Young African women (under age 30) face disproportionate HIV risk, accounting 
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for more than half of new infections on the continent, and with incidence rates that are often double or more than 
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their male age-mates.2-4 At the same time, African women also face a disproportionate burden of STIs. Globally, 
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the World Health Organization (WHO) estimates that 358 million new cases of four curable STIs – three bacterial 
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pathogens (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum [etiologic cause of syphilis]), 
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plus the parasite Trichomonas vaginalis – are acquired worldwide.5-7 Overall, the global burden of STIs is 
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greatest in low- and middle-income countries, and the overlapping epidemics of HIV and bacterial STIs in Africa 
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have been recognized since the earliest days of the HIV epidemic.8-12 The consequences of bacterial STIs on 
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sexual and reproductive health can be profound: pelvic inflammatory disease (PID), chronic pelvic pain, tubal 
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infertility, pregnancy complications, fetal and neonatal death, and increased susceptibility to HIV.8, 11, 13-17 These 
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consequences are overwhelmingly borne by women.  
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HIV pre-exposure prophylaxis (PrEP) is emerging into a global context with unprecedented rates of 
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curable STIs. The past decade has witnessed monumental strides in the development of highly-effective HIV 
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prevention interventions, including antiretroviral PrEP.18-21 PrEP reduces incident HIV but was not expected to 
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prevent other STIs, including gonorrhea, chlamydia, or syphilis. In high-income countries, like the US, the past 
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decade has seen an explosion in the incidence of bacterial STIs among MSM.22-24 The scale-up of PrEP in the 
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US and other settings with MSM-predominant epidemics is concurrent with this STI rise, although several other 
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major transitions are also occurring, including evidence for antiretroviral treatment as prevention (and the 
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undetectable=untransmittable [U=U] campaign)25, 26 and changing trends in sexual mixing patterns.27, 28 HIV and 
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STIs overlap in transmission pathways through sexual exposure; thus, it is not surprising that high STI rates are 
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seen among persons who use PrEP. The role of PrEP in driving changes in sexual behavior and increased risk 
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for STI acquisition among MSM using PrEP has been a source of substantial scientific and public health 
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debate.24, 29, 30  
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Post-exposure prophylaxis using the antibiotic doxycycline has been proposed as a novel STI 
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prevention strategy. Several recent open-label clinical trials among MSM in France (IPERGAY followed by 
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DOXYVAC) and the US (DoxyPEP) found a 47-70% relative reduction in new bacterial STIs (specifically, C. 
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trachomatis, N. gonorrhoeae, or T. pallidum) among PrEP users who also took doxycycline hyclate 200mg 
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following every sexual encounter.31, 32 This reduction was driven by reductions in incident C. trachomatis (70% 
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reduction) and T. pallidum infections (73% reduction). The use of post-exposure doxycycline to prevent infections 
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is already standard, recommended practice – for example, after tick exposure in areas of high Lyme disease 
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prevalence or after flooding in leptospirosis endemic areas.33-35 The concept of STI prophylaxis has a long 
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history,31, 36, 37 and several studies on single dose or monthly antibiotics, among female sex workers in Asia and 
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Africa, demonstrated reduced disease burden;38-43 a meta-analysis showed a statistically significant impact on 
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incidence of curable STIs in 13 of 14 studies included.37 The IPERGAY results31 were striking in the overall 
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reduction in incident STIs, good tolerability and safety, high adherence, and continuation (both >90%), and 
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without a significant change in sexual behavior in the intervention arm.31 These results were similar to results 
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among people assigned male sex at birth, taking HIV PrEP, and history of an STI in the prior year in the US with 
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70% reduction in C. trachomatis, T. pallidum, and N. gonorrhoeae.32 
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The first study of doxycycline postexposure prophylaxis for cisgender women did not reduce incident 
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STIs likely due to low use of doxycycline. The dPEP Kenya Study enrolled 449 cisgender women taking HIV 
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PrEP in Kisumu, Kenya. Participants were randomized 1:1 to open-label use of doxycycline hyclate 200mg within 
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72 hours of condomless sex compared with standard of care, or quarterly STI testing and treatment. Participants 
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in this study had high prevalence (18%) and annual incidence (27%) of bacterial STIs, primarily Chlamydia 
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trachomatis and Neisseria gonorrhoeae, with no statistical difference in frequency of quarterly incident STIs 
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between groups. Using objective measures of doxycycline use, doxycycline was only detected in approximately 
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1/3 of hair samples, and low use of doxycycline PEP contributed to a null result in this trial. Qualitative data 
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suggests that participants experienced multiple barriers to event-driven dosing.   
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Doxycycline was detectable in the serum and vaginal secretions at high levels for at least four days 
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following a single oral 
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dose 
of 
200mg 
oral 
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doxycycline hyclate per 
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recent 
pharmacokinetic 
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data (Figure 1).44 Limited 
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data 
on 
minimum 
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inhibitory 
concentration 
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(MIC) 
of 
doxycycline 
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needed to treat a C. 
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trachomatis 
infection 
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suggests that these high 
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levels 
of 
doxycycline 
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sustained for four days 
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are above the MIC. There 
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is no established MIC for 
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prevention, and due to a smaller bioburden of organisms with an initial exposure compared with an infection that 
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has already invaded tissue, it is presumed to be less than that needed for treatment.  
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Doxycycline prophylaxis could be especially impactful for African women using PrEP. Essentially all 
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global conversation about doxycycline for STI prevention has been directed towards MSM in high-income 
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settings, but the benefits might be especially great for women in Africa. Due to limited availability of etiologic STI 
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testing in Africa, few studies have assessed STI risk among PrEP-using women in Africa, but we have led several 
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studies among young African women that also contribute some of the only information about both STI prevalence 
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and incidence in that population (Table 1).45-48 In those studies, we are seeing very high STI rates, already 
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comparable to those seen 
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among PrEP-using MSM in 
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high income countries. Thus, 
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African women already carry 
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a striking burden of STIs, 
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reflecting likely high rates in 
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male partners as well, low 
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ability to negotiate condom 
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use, and great need for 
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prevention. 
PrEP 
roll-out 
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provides an opportunity to 
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impact both HIV and STI 
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rates in African women. First, 
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the consequences of STIs (PID, tubal infertility, complications of pregnancy) are arguably substantially greater 
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than those faced by MSM with pharyngeal or rectal STIs. Second, the current standard of care in Africa for STI 
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diagnosis is syndromic management, which has very poor sensitivity (<20%) compared to etiologic testing47 and 
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low positive predictive value (approx. 50%);49, 50 Doxycycline prophylaxis could be an inexpensive intervention in 
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settings where testing is unavailable or unaffordable. Third, doxycycline is affordable and accessible in Africa. 
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Fourth, weekly doxycycline does not rely on partner participation.  
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1.2. 
Rationale 
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Rationale for evaluation of Kenyan women 
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Table 1. High STI rates among young African women in three vanguard PrEP cohorts 
 
 
Chlamydia trachomatis
Neisseria gonorrhoeae
MTN-020/ASPIRE (phase III dapivirine ring 
trial) [Baeten, protocol chair] 
Prevalence = 12% 
 
Incidence = 27% per year 
Prevalence = 4% 
 
Incidence = 11% per year 
HPTN 082 (PrEP demonstration project) 
[Baeten, co-I]  
Prevalence = 29% 
 
Incidence = 33% per year 
Prevalence = 8% 
 
Incidence = 14% per year 
POWER (PrEP implementation project) 
[Baeten, protocol chairs, Bukusi, co-I] 
Prevalence = 26% 
 
Incidence = 53% per year 
Prevalence = 10% 
 
Incidence = 20% per year 
dPEP Kenya (doxycycline for STI prevention) 
[Stewart, protocol chair, Baeten/Bukusi, MPI] 
Prevalence = 14% 
Incidence = 21% per year 
Prevalence = 4% 
Incidence = 8% per year 
Note: Syphilis prevalence was <2% in these studies, with incidence <5% per year – emphasizing that the burden of STIs 
in this population is cervical infections. HSV-2 seroprevalence was ~50%. 

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Prior work on doxycycline post-exposure prophylaxis against bacterial STIs in Kisusmu, Kenya, demonstrated 
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high rates of STIs among cisgender women taking HIV PrEP and low use of doxycycline as an event-driven 
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post-exposure prophylaxis. The proposed study will focus on enrolling women, who far disproportionately bear 
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the global burden of morbidity and mortality from sexually transmitted infections. Thus, this work will ensure that 
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this potential prevention strategy is justly studied in women, and a specific focus on women is justified.  
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Rationale for weekly doxycycline dosing  
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Given low rates of use with event-driven 
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doxycycline PEP along with high rates of 
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STIs and extremely low rates of condom 
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use indicate a need for alternative 
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strategies for STI prevention and recent 
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pharmacokinetic data suggests that one 
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200mg dose a week results in four days 
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of doxycycline drug level above the 
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treatment MIC, which may be sufficient 
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for 
prevention 
of 
bacterial 
STIs 
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regardless of timing of exposure each 
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week, allowing for an opportunity for 
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supported dosing with Direct Observed 
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Therapy (DOT). Participants receiving a 
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weekly dose would have inhibitory 
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concentrations in vaginal secretions for four days of each week and then the following dose would be within 72 
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hours of the prior dose allowing for a pre-exposure and post-exposure combination approach to dosing that 
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would minimize pill burden and allow for added adherence support with directly observed dosing (Figure 2). 
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DOT in this study offers numerous advantages. By monitoring patients as they take their medication, DOT 
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ensures that any treatment failure detected is not due to missed doses of treatment51, leading to more accurate 
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data on treatment effectiveness. It also allows research staff to promptly identify and address potential side 
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effects or adverse reactions to medications. Furthermore, DOT contributes to better overall health outcomes by 
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reducing the likelihood of developing antibiotic resistance, as patients are more likely to complete their prescribed 
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treatment course. A standardized weekly DOT will also allow for crucial data collection needed to build a 
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pharmacokinetic model for interpreting quantitative concentrations of doxycycline in hair samples.  
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Doxycycline safety 
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Safety was a key consideration for the development and evaluation of PrEP, and similarly should be part of STI 
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PEP assessment. Data evaluating PrEP use in women at all stages of reproductive planning (desiring pregnancy, 
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achieving pregnancy, and in combination with hormonal contraceptives) have demonstrated safety, many of the 
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studies by our team.52-57 Doxycycline is well-tolerated and recent data show strong safety when used by women, 
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including in early pregnancy.34 Early data on tetracycline found bone and tooth effects when used in late 
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pregnancy, and cautions were extended to the entire tetracycline class, including doxycycline, despite lack of 
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drug-specific data.58 Tetracyclines are safe for use in lactating women but are not recommended at high doses 
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or extended courses due to theoretical risk of infant tooth discoloration.59, 60 Expert opinion is now calling for 
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reconsideration of doxycycline use in pregnant and lactating populations given significant differences between 
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doxycycline and tetracycline and lack of evidence showing adverse events with doxycycline exposure in pregnant 
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women.61 For women who do not desire pregnancy, there are no estrogen/progesterone and doxycycline drug-
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drug interactions, so doxycycline use will not alter hormonal contraceptive effectiveness.57 
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Potential for drug resistance  
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The potential for inducing drug-resistant STIs is an important concern for doxycycline prophylaxis. On one hand, 
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antibiotic resistance to tetracycline-class drugs is selected relatively easily in some bacteria (e.g., N. 
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gonorrhoeae); on the other hand, resistance for N. gonorrhoeae is common globally, making additional 
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resistance selection unlikely, but other organisms (e.g., C. trachomatis) have never demonstrated resistance. 
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Syphilis (Treponema pallidum) is at risk of developing tetracycline resistance; however, we anticipate very low 
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rates (<2%) of syphilis and thus in this population the risk of developing resistance is very low. In the dPEP 
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Kenya study, there was only 1 T.pallidum infection among 109 incident STIs reported. The dPEP Kenya Study 
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also revealed that 100% (n=48) of all N. gonorrhoeae infections were associated with a high level tetracycline 
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resistance molecular mutation, tetM, including at baseline and participants assigned to standard of care 
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indicating that further exposures to doxycycline could not increase the prevalence of resistance in Kisumu, 
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Kenya.62 In general, if weekly doxycycline is successful in preventing STIs, this dramatically reduces the risk of 
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resistance, as selection should only happen if infection is established and replication occurs despite antibiotic 
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pressure. Overall, we feel there are both important knowns and unknowns that define equipoise for this question, 
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and we have put strong strategies in place to measure and mitigate potential resistance risks. 
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2. OBJECTIVES 
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2.1. 
Primary Study Objectives:  
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1. Assess the acceptability of once weekly doxycycline prophylaxis 
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2. Assess persistence in once weekly doxycycline DOT 
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2.2. 
Secondary Study Objectives: 
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1. Evaluate incidence rate of STIs in women given once-weekly doxycycline DOT 
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2. Assess the safety and tolerability of once weekly doxycycline prophylaxis 
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3. Collect samples for future doxycycline hair drug level pharmacokinetic drug testing, rectal swabs 
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and endocervical swabs for resistance testing, and rectal and vaginal swabs for microbiome 
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evaluation.  
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3. METHODOLOGY 
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3.1. 
Design 
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Overview: The overarching goal is to assess acceptability and adherence to once-weekly doxycycline dosing to 
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prevent STIs through a pilot study.   
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Enrollment: Eligible participants will be assigned to doxycycline and will be given doxycycline 200 mg orally, 
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once weekly at the study clinic or within the community with a trained study staff as DOT. Study staff will record 
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confirmation of each dose taken. Enrollment visit will take place in the clinic to allow for provider collected sample 
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collection and delivery of first DOT.  
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Study visits: All participants will attend the clinic for quarterly visits after enrollment (Month 3 and Month 6). 
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Participants will provide provider-collected genital swab for STI testing. Treatment will be provided for any 
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positive test result. Hair samples  (50-100 strands) will be collected at Month 3 and Month 6 from all participants 
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with sufficient (>1cm) hair.  Month 6 exit visit will also include collection of samples for future microbiome and 
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resistance testing).  
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Study population: This study will enroll approximately 50 Kenyan women (maximum of 60) aged 18 and 30 
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years who are sexually active and using PrEP for HIV prevention. Participants must be willing to adhere to DOT 
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visits for the six month course of the study.  
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3.2. 
Selection and enrollment of participants  
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Potential participants will be screened for eligibility prior to enrollment in the study. The eligibility criteria are as 
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follows: 
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3.2.1. Inclusion criteria 
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1) Willing and able to give written informed consent 
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2) Age 18-30 years 
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3) Female sex at birth  
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4) HIV-seronegative, according to national HIV testing algorithm 
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5) Has a current prescription for PrEP, according to the national guidelines of Kenya 
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6) Able and willing to adhere to DOT dosing schedules 
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3.2.2. Exclusion criteria 
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1) Pregnant 
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2) Breastfeeding a child 
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3) Allergy to tetracycline class 
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4) Current medications which may impact doxycycline metabolism or that are contraindicated with 
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doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, 
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carbamazepine, phenytoin, and warfarin.  
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5) Active, clinically significant medical or psychiatric conditions that would interfere with study 
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participation, at the discretion of the site investigator or designee. 
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6) Prior enrollment in The dPEP Kenya Study 
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3.2.3. Recruitment  
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The study team will employ a variety of methods to recruit and screen potential participants in the Kisumu, Kenya 
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region and will use the same strategies as the dPEP Kenya Study to improve likelihood of enrolling a similar 
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cohort. The experienced community outreach team at the study site in Kisumu employs community-based 
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mobilization strategies, including engaging community health volunteers, gate keepers, peer-to-peer 
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mobilization, youth peer providers and ambassador models, use of printed and electronic IEC materials, social 
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media (WhatsApp and Facebook), radio talk shows in English, Kiswahili, and the local DhoLuo dialects, active 
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participation in local social events for information sharing, and partnering with learning institutions to give health 
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talks and to provide study related information. Careful attention to confidentiality is made in the recruitment 
409 
process and potential participants are never approached individually in group settings or public messaging. 
410 
Recruitment messaging is screened for cultural and community acceptability to reduce risk of stigma for study 
411 
participants. Potential participants who are not interested in the study or do not meet study eligibility criteria, may 
412 
be notified of alternative studies that they may be eligible for, or provided information about where to access 
413 
standard of care for HIV prevention and STI services.  
414 
 
415 
3.3. 
Study treatment  
416 
 
417 
3.3.1. Study product  
418 
Generic immediate release doxycycline hyclate 100 mg capsules will be provided by the study to participants 
419 
randomized to doxycycline DOT and will take two capsules once weekly for six months. Doxycycline hyclate is 
420 
a standard formulation of doxycycline that is widely available internationally and FDA approved for the treatment 
421 
of a number of infectious conditions. Doxycycline hyclate will be purchased from a quality-controlled supplier in 
422 
Kenya and with consultation by the Kenya National AIDS and STI Control Programme. Product suppliers will be 
423 
able to provide evidence of good manufacturing practices.  
424 
 
425 
3.3.2. Safety  
426 
Doxycycline is widely used for the treatment of chlamydia and other infections. Serious side effects are extremely 
427 
rare. 
428 
 
429 
The possible side effects of doxycycline are63, 64 
430 
 
Gastrointestinal upset: nausea, diarrhea, epigastric pain, and candidiasis 
431 
 
Esophageal disorders: dysphagia, pill esophagitis, and rarely esophageal ulceration. Risk for 
432 
esophageal irritation can be reduced by taking doxycycline capsules at least one hour before bedtime 
433 
(to avoid being lying down with doxycycline intake) at a meal with a glass of water (100 ml).  
434 
 
Skin reactions including maculopapular, erythematous, and photosensitivity skin reactions.  
435 
 
436 
3.3.3. Dispensing and administration 
437 
Doxycycline will be stored at the Kisumu site pharmacy at room temperature (59-86o F). Study pharmacists will 
438 
be responsible for dispensing and accountability of all study product.  
439 

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440 
Participants randomized to receive doxycycline will be advised on potential side effects and their management. 
441 
Participants will take their first dose of doxycycline at the study clinic. Thereafter, each dose will be provided 
442 
either at the study clinic, at a community location agreed upon by the participant and study staff, or at a 
443 
community pharmacy where study staff are available to provide DOT. Study staff carrying doxycycline outside 
444 
of the study clinic will keep the drug secure and within temperature range to the extent possible. Accountability 
445 
logs and study case report forms will document the administration of doxycycline. Doxycycline may be taken on 
446 
an empty stomach or with food, and it is advised to take with a large glass of water to reduce risk of esophageal 
447 
irritation and with food to reduce nausea.  
448 
 
449 
3.3.4. Concomitant Medications  
450 
Participants should report current and new medications to the study team to ensure no concern for drug 
451 
interactions. The prescribing information for doxycycline hyclate and azithromycin should be reviewed to ensure 
452 
no potential for drug interactions. Medications that interact with doxycycline include barbiturates, carbamazepine, 
453 
phenytoin, methoxyflurane, acitretin, isotretinoin, and warfarin.  
454 
 
455 
3.4. 
Study procedures 
456 
An overview of study procedures is provided in Table 2. Participants will also have weekly visits as described 
457 
below. 
458 
 
459 
Table 2. Schedule of study procedures. 
460 
Study Visit 
S
E
3
6
 
Administrative 
 
Obtain informed consent 
X 
 
 
 
Screen for inclusion/exclusion 
X 
X 
 
 
Collect updated contact information 
X 
X 
X 
X 
Reimbursement 
X 
X 
X 
X 
 
Surveys 
 
Demographic information 
X 
X 
 
 
Acceptability  
 
X 
X 
X 
Sexual behavior  
 
X 
X 
X 
 
Clinical care 
 
Medication review 
X 
X 
X 
X 
General symptom assessment 
 
X 
X 
X 
WHO pregnancy checklist 
X 
 
X 
X 
STI symptom assessment 
X 
X 
X 
X 
 
Counseling 
 
STI/HIV risk reduction counseling  
X 
X 
X 
X 
Condom provision 
X 
X 
X 
X 
 
Clinical Testing 
 
HIV testing (rapid test) 
X 
 
X 
X 
Urine pregnancy testing 
(X) 
X 
(X) 
(X) 
CT/NG testing Xpert (endocervical swab) 
 
X 
X 
X 
Syphlis testing (serum RPR) 
 
X 
X 
X 
 
Archived Sample Collection 
 
Hair collection for drug level testing (stored) 
 
 
X 
X 
Aptima CT/NG endocervical swab (stored) 
 
X 
X 
X 
Endocervical swabs for resistance (stored) 
 
X 
 
X 
Rectal swabs for resistance (stored) 
 
X 
 
X 

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Vaginal swabs for microbiome (stored) 
 
X 
 
X 
 
461 
3.5. 
Study visits  
462 
 
463 
Specific study procedures are detailed in Table 2.0. Study visits will take place at screening/enrollment, 
464 
Month 3, and Month 6 with additional weekly DOT delivery of doxycycline. We will conduct tracing in the 
465 
case of missed visits to ensure that missed visits are minimized regardless of whether or not doxycycline is 
466 
continued. All participants will provide clinical and behavioral data. We will use electronic data capture for 
467 
surveys and case report forms. All participants will receive reimbursement for their time and effort for each 
468 
visit, in accordance with local regulatory and ethics approvals. 
469 
 
470 
3.5.1. Screening Visit:  
471 
 
Potential participants will be screened for inclusion and exclusion criteria, and those eligible will be invited 
472 
to enroll. Potential participants will provide written informed consent before any research procedures are 
473 
completed. Participants will be screened for symptoms of STIs, and treated empirically if symptomatic (per 
474 
Kenyan National Guidelines). Pregnancy will be assessed using the WHO pregnancy check list and a 
475 
pregnancy test. If the woman is pregnant, she will not be eligible for enrollment and will be referred for 
476 
antenatal services. 
477 
 
478 
3.5.2. Enrollment Visit:  
479 
The enrollment visit will be as soon as the following day after screening visit and as late as 28 days following 
480 
the screening visit. Demographic, behavioral, and medical information will be collected. Prior to 
481 
administration of doxycycline, providers will complete a pelvic exam and genital sample collection for 
482 
CT/NG testing (NAAT Xpert), and future resistance and microbiome testing. Additionally, two rectal swabs 
483 
will be collected: one for future resistance testing and one for future Aptima testing. Participants with an 
484 
STI at enrollment will complete treatment. Women will be tested for pregnancy with urine rapid pregnancy 
485 
test at enrollment regardless of contraceptive use, and may also receive a referral for contraception, if 
486 
desired. All potential participants will be screened for HIV, following national HIV testing guidelines. Women 
487 
who have a positive HIV test will be referred for HIV care and treatment and counseled on discontinuation 
488 
of HIV PrEP.  
489 
 
490 
3.5.3. Follow-up clinic visit (Month 3): 
491 
All participants will visit the study clinic at three months (+/- two weeks) after enrollment. Participants will 
492 
be tested for STIs using provider collected endocervical swab (CT/NG) and blood (syphilis) as well as blood 
493 
for HIV testing. An additional endocervical Aptima swab will be collected for future testing if needed. If a 
494 
participant has signs or symptoms of an STI, she will be provided with syndromic management and 
495 
treatment or following receipt of the STI results if willing to wait for same day results. Participants will also 
496 
be asked to provide a hair sample (50-100 strands) to be used for drug-level testing in the future. Behavioral 
497 
questionnaires will be administered, including sexual behavior and acceptability. Participants will be asked 
498 
about adverse events and any changes to their medical history or concomitant medication use. 
499 
 
500 
3.5.4. Exit clinic visit (Month 6): 
501 
All participants will visit the study clinic at six months (+/- two weeks) after enrollment. Participants will be 
502 
tested for STIs using provider collected endocervical swab (CT/NG) and blood (syphilis) as well as blood 
503 
for HIV testing. An additional endocervical Aptima swab will be collected as well as endocervical and rectal 
504 
swab for resistance testing in the future and vaginal swab for microbiome testing in the future, which will 
505 
all be stored and archived. If a participant has signs or symptoms of an STI, she will be provided with 
506 
syndromic management and treatment or following receipt of the STI results if willing to wait for same day 
507 
results. Participants will also be asked to provide a hair sample (50-100 strands) to be used for drug-level 
508 
testing in the future. Behavioral questionnaires will be administered, including sexual behavior and 
509 
acceptability. Participants will be asked about adverse events and any changes to their medical history or 
510 
concomitant medication use. 
511 
 
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3.5.5. Doxycycline DOT visits: 
513 
 
514 
Participants will have once-weekly visits (every 7 days +/- 1 day) to receive doxycycline for up to six months 
515 
of follow-up. Participants may meet with study staff at the clinic, outside of the clinic at an agreed upon 
516 
place with a trained peer-navigator, or at pre-specified community pharmacies where KEMRI staff are 
517 
located.  
518 
 
519 
Participants will be provided with 200mg doxycycline hyclate each week as DOT and study staff will record 
520 
observation of dosing or reason for missed dose on study CRFs.  
521 
 
522 
 
523 
3.5.6. Unscheduled interim visits:  
524 
Women may return to the study clinic for interim visits for any reason and can undergo STI testing and 
525 
treatment if STI symptoms are present. Additionally, participants concerned about any adverse event from 
526 
the study drug are invited to return to study provider evaluation and management.  
527 
 
528 
 
529 
3.5.7. Sample collection and outcome measures:  
530 
Primary study outcome: Confirmation of DOT dosing each week will be recorded on weekly CRFs and 
531 
quarterly surveys on acceptability will be completed. 
532 
  
533 
STI testing: Provider collected endocervical swabs will be used for STI (CT/NG) testing as well as blood 
534 
testing for syphilis at Months 3 and 6. An additional Aptima swab will be collected for CT/NG testing.  
535 
 
536 
Doxycycline drug level testing: As an objective measure of doxycycline use, hair samples will be tested 
537 
for doxycycline drug levels. The weekly doxycycline dosing will be used to develop and validate a 
538 
standardized pharmacokinetic model for doxycycline hair concentrations that will also be used to interpret 
539 
results of hair samples collected from from the The dPEP Kenya Study that was carried out by our team 
540 
in Kisumu Kenya.  
541 
 
542 
Resistance testing: Providers will collect endocervical and rectal swabs at enrollment and Month 6, to be 
543 
stored for future NG and enteric organism resistance testing.  
544 
 
545 
Microbiome testing: Providers will collect vaginal swabs at enrollment and Month 6, to be stored for future 
546 
microbiome testing.  
547 
 
548 
 
549 
3.5.8. Laboratory Procedures: 
550 
 
551 
Samples will be tested within Kenya where feasible. All diagnostic tests will be done at our laboratory in Kisumu. 
552 
Any samples that require specialized testing will be shipped to the University of Washington (UW) and/or other 
553 
laboratories described below. For hair samples doxycycline testing, we have no laboratory with capacity to test 
554 
this in Kenya and the only laboratory that specializes in this analysis is at the University of California, San 
555 
Francisco, where we will be sending the hair samples for analysis. Resistance and microbiome swabs for future 
556 
will be stored and tested at Dr. Soge’s lab at the University of Washington.  
557 
 
558 
3.5.8.1. 
STI testing: 
559 
All STI screening will be completed with same day testing in Kisumu, Kenya (Cepheid GeneXpert) or in 
560 
the laboratory of Dr. McClelland in Mombasa, Kenya, operating with external quality assurance for >10 
561 
years (Aptima Combo 2). Vaginal swabs will be tested for C. trachomatis and N. gonorrhoeae by nucleic 
562 
acid amplification testing (NAAT). Syphilis will be tested by rapid plasma reagin (RPR) titers (BD Macro-
563 
Vue) with Treponema pallidum hemagglutination assay (TPHA) confirmatory testing (Fortress 
564 
Diagnostics) using plasma samples in the Kisumu KEMRI-RCTP lab.  
565 
 
566 

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3.5.8.2. 
Resistance testing:  
567 
Endocervical samples will be shipped to the University of Washington laboratory of Dr. Soge for possible 
568 
future molecular testing of N. gonorrhoeae for high-level tetracycline resistance (tetM). DNA will be 
569 
purified from residual endocervical NAAT samples and endocervical swabs using the High Pure DNA Kit 
570 
(Roche Diagnostics, Indianapolis, IN). Swabs containing organisms will similarly be archived at University 
571 
of Washington for future evaluation of doxycycline resistant enteric commensals (e.g., Eschericia coli, 
572 
Enterococcus spp., Enterobacter spp., and Shigella spp.) 
573 
 
574 
3.5.8.3. 
Drug-level testing: 
575 
Hair sample will be collected for future testing of drug levels for a more objective assessment of exposure 
576 
to doxycycline. Hair samples (50-100 strands) will be collected following consent to collection and 
577 
confirmed eligibility for hair collection (occipital hair >1cm in length with absence of bleaching) from all 
578 
participants at each follow-up visit (Months 3 and 6). In the future, hair samples will be shipped to Dr. 
579 
Monica Gandhi’s UCSF Hair Analytical Laboratory (HAL). 
580 
 
581 
3.5.8.4. 
Microbiome testing:  
582 
We will archive vaginally collected foam tip swabs at -80C for potential future testing to evaluating 
583 
potential changes in microbiome following initiation and continuation of weekly doxycycline.  
584 
 
585 
3.5.9. Management and treatment of STIs 
586 
 
587 
Participants found to have a diagnosis of gonorrhea, chlamydia, or syphilis will be contacted by study 
588 
staff or provider regarding their new diagnosis. Participants will be offered prompt treatment (single dose 
589 
azithromycin tablets, ceftriaxone intramuscularly (IM) once or benzathine penicillin G intramuscularly 
590 
once) at the study clinic. If there is a delay in treatment, participants with known STIs will have doxycycline 
591 
DOT held until the day after they complete their single dose treatments. Participants with clinical concern 
592 
for complicated STI (i.e., PID) will be offered prolonged treatment (single dose IM ceftriaxone and 2 week 
593 
course of azithromycin and metronidazole) and doxycycline DOT will be held for the duration of treatment. 
594 
Participants will be encouraged to tell partners to also be treated per Kenya guidelines and offered 
595 
expedited partner therapy (EPT). Counselling on STI prevention strategies will be provided to all 
596 
participants during treatment. 
597 
 
598 
3.5.10. Risk compensation counselling 
599 
 
600 
To mitigate against potential risk compensation arising from sense of safety due to use of doxycycline for 
601 
prevention of STIs, participants will receive specific counselling emphasizing on the unknown efficacy of 
602 
the study medication as used in the study. Participants will also be provided with condoms for free should 
603 
they need them. At each study visit, participants will receive general counselling on STI and HIV 
604 
prevention strategies. 
605 
 
606 
3.5.11. Management of HIV-seroconversion 
607 
 
608 
If a participant tests HIV positive, following national testing algorithms, study clinicians will follow national 
609 
guidelines for discontinuing PrEP. Women will be referred to the nearest HIV care clinic for initiation of 
610 
antiretroviral therapy. Women who seroconvert will remain in the study through the end of their scheduled 
611 
follow-up and will be permitted to continue taking doxycycline. 
612 
 
613 
3.5.12. Management of doxycycline with contraceptives and pregnancy  
614 
 
615 
Contraceptives will be offered on-site but will not be required for study participation. The effectiveness of 
616 
contraceptives or doxycycline will not change with concomitant use. Women will be counseled on current 
617 
Kenyan guidelines, which do not recommend use of doxycycline in pregnant women, due to lack of safety 
618 
data, and participants will stop doxycycline should pregnancy occur. Women, who are not using LARC, 
619 
will be screened for possible pregnancy at each quarterly visit using the WHO pregnancy checklist and if 
620 

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needed a urine pregnancy test will be conducted. Women can resume weekly doxycycline when no longer 
621 
pregnant or breastfeeding. Pregnancies will be followed to completion. Any babies born to participants 
622 
during the trial period will be passively followed and asked about the health of their baby. Breastfeeding 
623 
will be an exclusion criterion for the trial, to limit exposure prior to demonstration of effectiveness; 
624 
doxycycline is generally felt to be safe at standard doses in lactating women, although no formal 
625 
declaration of safety exists for this population. Doxycycline is well-tolerated and recent data emphasize 
626 
a strong safety profile when used by women, including in early pregnancy, and children. Early data on 
627 
safety of tetracycline found potential adverse effects when used in late pregnancy (specifically, bone and 
628 
tooth effects), and cautions were extended to the entire tetracycline class, including doxycycline, despite 
629 
lack of drug-specific data.133,136 Expert opinion is now calling for reconsideration of doxycycline use in 
630 
pregnancy given significant differences between doxycycline and tetracycline and lack of evidence 
631 
showing adverse events with doxycycline exposure in pregnant women.  
632 
 
633 
3.6. 
Adverse Events (AE) And Study Monitoring 
634 
 
635 
3.6.1. Adverse Event Collection Requirements 
636 
3.6.1.1. 
Adverse Events (AEs) 
637 
The following AEs will be recorded on data collection forms: 
638 
 
All AEs that are attributed to study product in the opinion of the site investigator 
639 
 
All AEs meeting SAE definition  
640 
 
641 
3.6.1.2. 
Serious Adverse Events (SAEs) 
642 
An SAE is defined as any untoward medical occurrence that: 
 
 
643 
 
Results in death 
644 
 
Is life-threatening  
645 
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
646 
 
Results in persistent or significant disability/incapacity  
647 
 
Is a congenital anomaly/birth defect 
648 
 
Is an important medical event that may not be immediately life-threatening or result in death or 
649 
hospitalization but may jeopardize the patient or may require intervention to prevent one of the other 
650 
outcomes listed in the definition above 
651 
 
652 
All AEs that are recorded must have their severity graded. To grade AEs, sites should refer to the most recent 
653 
version of Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE 
654 
Grading Table).  
655 
 
656 
3.6.2. Study Monitoring 
657 
 
658 
The study team will monitor the conduct of the study through summary reports of accrual, baseline characteristics 
659 
and reports of data pooled over treatment arms of data completeness, specimen collection, and AEs. The study 
660 
team will review individual participant-level safety data frequently to assess the relation of all reported AEs to 
661 
study treatment. The study team will review premature study discontinuations or premature study treatment 
662 
discontinuations on a case-by-case basis.   
663 
 
664 
3.7. 
Medical Monitoring Committee 
665 
 
666 
We will constitute an independent medical monitoring committee composed of a variety of experts on 
667 
doxycycline prophylaxis and sexual and reproductive health research, drawn from Kenya and 
668 
internationally. The committee membership will be restricted to individuals free of significant conflicts of 
669 
interest. This committee will meet prior to enrollment, 33% completion of study follow up time, and 66% 
670 
completion of study follow up time. The committee will track side effects, potential safety concerns 
671 

17                                   
DoxyDOT 
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associated with study participation, and fidelity to this open-label, single study arm, pilot study protocol. 
672 
Open study reports containing enrollment and retention rates, participant characteristics, adverse events, 
673 
and social harms, will be sent to the committee members at least one week prior to each meeting. All 
674 
medical monitoring meeting reports will be shared with the overseeing ethics review committee within 
675 
two weeks of each meeting or earlier per requirements of each ethics committee. 
676 
 
677 
3.8. 
Criteria for discontinuation 
678 
 
679 
Participants will continue in the study, regardless of medication or study visit adherence, with the exceptions 
680 
listed below.  
681 
 
682 
3.8.1. Premature Study Treatment Discontinuation 
683 
 
Requirement for prohibited concomitant medications or other contraindication to doxycycline 
684 
 
Occurrence of an AE requiring discontinuation of study product  
685 
 
Request by participant to terminate study treatment 
686 
 
Clinical reasons believed life threatening by the physician, even if not addressed in the toxicity section 
687 
of the protocol 
688 
 
689 
Participants who stop study treatment should be continued on study, with continued evaluations. The 
690 
reason for treatment discontinuation should be recorded.  
691 
 
692 
3.8.2. Premature Study Discontinuation 
693 
 
Request by the participant to withdraw 
694 
 
Participant judged by the investigator to be at significant risk of failing to comply with the provisions 
695 
of the protocol as to cause harm to self or seriously interfere with the validity of the study results 
696 
 
At the discretion of the IRB/EC, funder, or Office for Human Research Protections (OHRP) 
697 
 
698 
3.9. 
Statistical Considerations 
699 
3.9.1. Outcome measures  
700 
 
701 
3.7.1.2. Primary outcome:  
702 
Percentage of completed doses of weekly doxycycline DOT 
703 
 
704 
3.7.1.3. Secondary outcomes:  
705 
 Safety: Safety assessment will be measured in both arms: serious adverse events (SAEs), related all 
706 
AEs and discontinuations (in the dPEP arm only), and a standardized symptom assessment for 
707 
doxycycline-specific side effects (e.g., nausea, pill esophagitis, photosensitivity, vaginal candidiasis). 
708 
 Acceptability: Longitudinal change in survey responses 
709 
 Incidence of C. trachomatis based on NAAT  
710 
3.9.2. Statistical power and analysis   
711 
3.9.2.1. 
Primary Analysis:  
712 
We will describe the percentage of completed doses of weekly doxycycline DOT of the 26 anticipated 
713 
doses per participant, and evaluate measured rate of completion with anticipated adherence of greater 
714 
than 80% of planned weekly doxycycline DOT doses completed, excluding any dose held for clinical 
715 
reason (e.g., pregnancy, severe adverse reaction, etc). 
716 
 
717 

18                                   
DoxyDOT 
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3.9.2.2. 
Secondary Analysis:  
718 
We propose comparing weekly doxycycline DOT with being assigned to standard of care in recently 
719 
completed dPEP Kenya Study. The dPEP Kenya Study was a randomized controlled trial in which 
720 
participants were assigned in a 1:1 ratio to doxycycline post-exposure prophylaxis (doxycycline hyclate 
721 
200mg) along with quarterly STI testing or to standard of care, defined as quarterly STI testing and 
722 
treatment alone among whom baseline rates of STIs were high at 17.9% with 14.1% prevalence of 
723 
chlamydia, 3.8% with gonorrhea, and 0.4% with syphilis.   
724 
 
725 
The secondary trial outcome will be the combined incidence of incident C. trachomatis, N. gonorrhoeae, 
726 
and syphilis, compared between the weekly doxycycline DOT and SOC from dPEP Kenya Study, 
727 
analyses will also test C. trachomatis alone.  
728 
 
729 
Analyses for this pilot study will be descriptive among all women and among those who achieve perfect 
730 
DOT dosing. STI incidence will be compared between groups using time to first event cox proportional 
731 
hazard analysis. Additional comparisons will be done using repeated measures analysis of proportions 
732 
(e.g., generalized estimating equations [GEE]), given possibility of repeat infection within individuals. 
733 
Adjusted analyses will be done as needed, controlling for potential confounders: demographics (e.g., 
734 
age, education), sexual behavior (e.g., condom use, # partnerships), and acceptability. SAS or R will be 
735 
used. 
736 
 
737 
3.10. Biohazard Containment 
738 
 
739 
As the transmission of HIV and other blood-borne pathogens can occur through contact with contaminated 
740 
needles, blood, and blood products, appropriate blood and secretion precautions will be employed by all 
741 
personnel in the drawing of blood and shipping and handling of all specimens for this study, as currently 
742 
recommended by the CDC and the National Institutes of Health. All non-blood biological samples will also be 
743 
handeled by study team with appropriate precautions per standard clinical and laboratory guidelines.  
744 
 
745 
All dangerous goods and materials, including diagnostic specimens and infectious substances, will be 
746 
transported using packaging mandated by CFR 42 Part 72. Please refer to instructions detailed in the 
747 
International Air Transport Association (IATA) Dangerous Goods Regulations.  
748 
 
749 
4. ETHICAL CONSIDERATION 
750 
 
751 
4.1. 
Institutional Review Board (IRB) Review  
752 
The study protocol, informed consent forms, participant education and recruitment materials, and other 
753 
requested documents—including any subsequent modifications—will be reviewed and approved by the UW IRB,  
754 
KEMRI SERU, and PPB ECCT in accordance with their requirements; they will be responsible for oversight of 
755 
research conducted at the study site. Subsequent to initial review and approval, the UW IRB and KEMRI SERU 
756 
will review the study at least annually.  
757 
 
758 
4.2. 
Informed Consent  
759 
Written informed consent will be obtained from all study participants prior to any research procedures. 
760 
Participants will be offered copies of the informed consent forms. Forms will be translated into local languages 
761 
and verified by performing an independent back-translation. Informed consent forms will be kept in a secure and 
762 
locked location for a period of at least 3 years following completion of the trial, longer if required by local 
763 
regulations or requirements of overseeing IRBs/ECs.  
764 
 
765 
4.3. 
Study records  
766 
The study site will establish a standard operating procedure for confidentiality protection. Each site will ensure 
767 
that study records including administrative documentation and regulatory documentation as well as 
768 
documentation related to each participant enrolled in the study, including informed consent forms, locator forms, 
769 

19                                   
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case report forms, notations of all contacts with the participant, and all other source documents are stored in a 
770 
secure manner.   
771 
 
772 
4.4. 
Confidentiality  
773 
Every effort will be made to protect participant privacy and confidentiality to the extent possible. Personal 
774 
identifying information will be retained at the Kisumu study site and not forwarded to any collaborating institutions 
775 
or labs; instead, all information will be identified only by a study ID number. The site will use their standard 
776 
operating procedure for confidentiality protection that reflects the input of study staff and community 
777 
representatives to identify potential confidentiality issues and strategies to address them. 
778 
  
779 
All study-related information will be stored securely at the study sites. All participant information will be stored in 
780 
areas with limited access. Data collection, administrative forms, laboratory specimens, and other reports will be 
781 
identified only by the study ID number to maintain participant confidentiality. All local databases will be secured 
782 
with password-protected access systems. Forms, lists, logbooks, appointment books, and any other listings that 
783 
link participant ID numbers to other identifying information will be stored in a separate, locked file in an area with 
784 
limited access. 
785 
 
786 
4.5. 
Participants’ rights under data protection laws  
787 
 
788 
Participants have the right to access, correct, and restrict the use of their data at any time during the study. 
789 
Participants also have the right to report a complaint to the local data protection authority: Data Protection 
790 
Commissioner, Ministry of ICT, Innovation and Youth Affairs, Teleposta Towers, Kenyatta Avenue off Koinange 
791 
Street, P.O Box 30025-00100, Nairobi – Kenya, Telephone: (+254) 020 4920000 / 1. Email: 
792 
info@information.go.ke. Participants can object at any time to their data being used for the study, however, in 
793 
that case, participants will also have to stop participation in the study. Participants can exercise these rights 
794 
through the study staff. These details will be included in the informed consent forms, a copy of which will be 
795 
given to all participants. 
796 
 
797 
4.6. 
Risks/Benefits 
798 
Participants may experience pain or discomfort during blood draws and pelvic exams. They may be 
799 
embarrassed or worried about the STI and HIV testing conducted during the study. Study questionnaires 
800 
asking information about sexual behavior or partners may also make the participant uncomfortable or 
801 
embarrassed. All study staff are trained to provide professional care in both clinical sample collection and 
802 
counseling and administering study questionnaires.  
803 
 
804 
There are known side effects to doxycycline, as listed in protocol section X.X. Participants will be counseled on 
805 
the side effects and ways to take the medication in order to minimize the impact of any side effects. 
806 
Participants will be encouraged to come to the study clinic if they have any concerns about the medication or 
807 
side effects they are experiencing.  
808 
 
809 
Study staff will make every effort to protect participants’ privacy and confidentiality. It is possible that 
810 
participants' involvement in the study could become known to others, and that social harms may result (i.e., 
811 
because participants could become known as participating in a trial involving sexually active women or persons 
812 
using PrEP).  For example, participants could be treated unfairly or discriminated against, or could have 
813 
problems being accepted by their families and/or communities. It is possible that participants may have 
814 
problems with their partner or experience intimate partner violence. Counseling and referrals will be available, 
815 
if needed. To mitigate against social harms from study participation, participants will have the opportunity to 
816 
attend their weekly visits at safe spaces and to bring their partners to the research clinic for explanation of the 
817 
study, for STI treatment and for counselling in case of positive STI results, alongside partner notification letters 
818 
with contact information of the study doctor and expedited partner treatment. 
819 
 
820 
Participants may benefit from their study participation as they will be receiving free STI testing and treatment 
821 
that is not readily available in public clinics. Prompt treatment of STIs, including asymptotic STIs, is beneficial 
822 

20                                   
DoxyDOT 
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to women in order to reduce the risk of pelvic pain, infertility, or other problems with future pregnancies that 
823 
can develop when STIs go untreated.  
824 
 
825 
4.7. 
Reimbursement  
826 
 
827 
Participants will be provided reimbursement for their travel costs and compensation of time spent during study 
828 
visits, in accordance with local guidelines and regulatory approvals. 
829 
 
830 
4.8. 
COVID-19 safety measures  
831 
The Coronavirus Disease 2019 (COVID-19) pandemic continues to evolve and participant safety will remain a 
832 
top priority in all study procedures. Study staff will follow all relevant local, national and WHO guidelines for 
833 
minimizing exposure risk to participants, including but not limited to safety training, wearing appropriate personal 
834 
protective equipment (PPE), and enforcing social distancing. Specific procedures will be documented in a 
835 
standard operating procedures (SOP) and updated as needed, particularly as more information about best 
836 
practices for reducing COVID-19 transmission becomes available. During the consenting process, participants 
837 
will be advised of the potential COVID-19 transmission risks related to in-person study procedures and the site 
838 
procedures in place to minimize this risk.   
839 
 
840 
4.9. 
Dissemination and utilization of study findings 
841 
 
842 
Our findings will be disseminated at the County, National and International level in the form of presentations 
843 
and policy briefs to the Kisumu County Health Management Teams, relevant National AIDS and STIs Control 
844 
Program (NASCOP) technical working groups, relevant stakeholder organizations, and at regional and 
845 
international scientific conferences. Our manuscripts will also be published as open access articles available to 
846 
the public free of charge. 
847 
 
848 
Findings from this study will provide key evidence to policymakers to support the implementation of STI 
849 
prevention within PrEP delivery programs in Kenya. The results will also be useful to other researchers 
850 
considering similar studies in other populations / countries. 
851 
 
852 
5. TIMELINE 
853 
 
854 
Table 3. Study timeline. 
855 
Table 3. Timeline
Q3 2023
Q1 2024
Q2 2024
Q3 2024
IRB and Ethics approval 
 
 
 
 
Research staff training
Data collection - Aims 1 and 2 
 
 
 
 
Data 
analysis, 
dissemination, 
and manuscript development 
 
 
 
 
 
856 
 
857 
 
858 
 
859 
 
860 
 
861 
 
862 
 
863 
 
864 

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