WHO-recommended Periodic Presumptive Treatment Versus Doxycycline Post-Exposure Prophylaxis for STI Control Among Cisgender Men Who Have Sex With Men in Kenya
Phase: PHASE4
Conditions: Gonorrhea Male, Chlamydia (Male), Syphilis Male
Sponsor: University of Washington

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WHO-Recommended Periodic Presumptive Treatment versus Doxycycline 
Post-Exposure Prophylaxis for STI Control among Cisgender Men Who Have 
Sex with Men in Kenya 
 
 

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Table of contents 
1. 
TITLE OF THE PROJECT .......................................................................................................................... 4 
2. 
INVESTIGATORS AND INSTITUTIONAL AFFILIATIONS ............................................................................. 4 
3. 
ABSTRACT ............................................................................................................................................ 4 
4. 
LAY SUMMARY .................................................................................................................................... 5 
5. 
INTRODUCTION/BACKGROUND ........................................................................................................... 6 
6. 
PROBLEM STATEMENT ......................................................................................................................... 6 
7. 
JUSTIFICATION FOR THE STUDY .......................................................................................................... 10 
8. 
HYPOTHESES ...................................................................................................................................... 10 
9. 
OBJECTIVES ........................................................................................................................................ 10 
10. METHODOLOGY ................................................................................................................................. 11 
A. 
STUDY SITES ................................................................................................................................................ 11 
B. 
STUDY DESIGN ............................................................................................................................................. 11 
C. 
STUDY POPULATIONS ..................................................................................................................................... 11 
D. 
SAMPLE SIZE DETERMINATION ......................................................................................................................... 12 
E. 
STAKEHOLDER ENGAGEMENT AND RECRUITMENT PROCEDURES .............................................................................. 13 
F. 
STUDY PROCEDURES ...................................................................................................................................... 13 
G. 
LIMITATIONS AND ALTERNATIVE APPROACHES .................................................................................................... 23 
11. DATA MANAGEMENT AND ANALYSIS ................................................................................................. 25 
A. 
DATA COLLECTION ........................................................................................................................................ 25 
B. 
DATA STORAGE ............................................................................................................................................ 26 
C. 
DATA ANALYSIS ............................................................................................................................................ 26 
12. ETHICAL CONSIDERATIONS ................................................................................................................ 29 
A. 
RISKS TO HUMAN SUBJECTS ............................................................................................................................ 29 
B. 
ADEQUACY OF PROTECTION FROM RISKS ........................................................................................................... 30 
C. 
POTENTIAL BENEFITS TO THE SUBJECTS AND OTHERS ........................................................................................... 32 
D. 
INFORMED CONSENT ..................................................................................................................................... 32 
E. 
CONFIDENTIALITY OF INFORMATION OBTAINED ................................................................................................... 33 
F. 
DATA SHARING ............................................................................................................................................. 35 
G. 
DATA SAFETY AND MONITORING PLAN .............................................................................................................. 35 
H. 
DATA SAFETY AND MONITORING BOARD ............................................................................................................ 37 
I. 
HANDLING ADVERSE EVENTS ........................................................................................................................... 37 
13. EXPECTED APPLICATION OF THE RESULTS ........................................................................................... 38 
14. TIME FRAME/DURATION OF THE PROJECT ......................................................................................... 38 
15. BUDGET ............................................................................................................................................. 38 
16. BUDGET JUSTIFICATION ..................................................................................................................... 39 
17. ROLE OF INVESTIGATORS ................................................................................................................... 39 
18. REFERENCES ...................................................................................................................................... 40 
19. APPENDICES ...................................................................................................................................... 46 

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Abbreviations 
ACASI 
 
Audio computer-assisted self interview  
AMR 
 
Antimicrobial resistance 
ART         
 
Antiretroviral therapy 
AST  
 
Antimicrobial sensitivity testing 
CAPI 
 
Computer assisted personal interview 
CT  
 
Chlamydia trachomatis 
doxyPEP 
 
Doxycycline post-exposure prophylaxis 
HIV  
              Human immunodeficiency virus 
LGBT  
 
Lesbian, gay, bisexual and transgender  
MHRC 
 
MSM health research consortium 
MPI 
 
Multiple principal investigators 
MoH 
 
Ministry of Health 
MSM 
 
Men who have sex with men 
NAAT 
 
Nucleic acid amplification testing 
NASCOP 
 
National AIDS & STI Control Programme 
NG  
 
Neisseria gonorrhoeae 
NRHS                          Nyanza Reproductive Health Society  
POC 
 
Point-of-care 
PPT  
 
Periodic presumptive treatment 
PrEP 
 
Pre-exposure prophylaxis 
RAI  
 
Receptive anal intercourse 
RPR 
 
Rapid plasma reagin 
sSA  
 
sub-Saharan Africa 
STI  
 
Sexually transmitted infections 
SWOP 
 
Sex Worker Outreach Program 
TGW                  
Transgender women 
UW  
 
University of Washington 
WHO 
 
World Health Organization 
 
 

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1. Title of the Project 
WHO-Recommended Periodic Presumptive Treatment versus Doxycycline Post-Exposure 
Prophylaxis for STI Control among Cisgender Men Who Have Sex with Men in Kenya 
[Protocol Number] SERU  
2. Investigators and Institutional Affiliations 
 
 
 
 
 
 
 
N.B. Investigator CVs are included in the appendices. 
Sponsoring Institution/Clinical Research Centre:  
University of Washington/Pwani Research Centre at the Ganjoni Municipal Clinic, Mombasa 
3. Abstract  
Men who have sex with men (MSM) are at high risk for gonorrhoea and chlamydia in Kenya, where 
nucleic acid amplification testing (NAAT) is not feasible, and most infections therefore go 
undiagnosed. In 2011, the WHO recommended periodic presumptive treatment (PPT) of Neisseria 
gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections for MSM at high risk for HIV 
acquisition due to condomless anal intercourse with multiple sex partners or a recent STI 
exposure. More recently, trials in well-resourced settings have demonstrated the efficacy of 
doxycycline post-exposure prophylaxis (doxyPEP) for reducing NG, CT, and syphilis infections 
among high-risk MSM. The goal of this study is to evaluate the impact and cost-effectiveness of 
WHO-recommended PPT versus doxyPEP compared to standard syndromic treatment among 
Kenyan MSM. This study aims to (1) evaluate the effectiveness and impact on antimicrobial 
resistance in NG of WHO-recommended PPT given every 3 months and of doxy-PEP taken 24-72 
hours after condomless sex for reducing STI burden among Kenyan MSM; (2) assess the 
acceptability, feasibility, and safety of implementing WHO-recommended PPT and doxy-PEP 
compared to standard care among providers and patients; and (3) model the health and economic 
impact of scaling up WHO-recommended STI PPT and doxyPEP compared to standard of care on 
STI control among MSM and their partners in Kenya. We will conduct an open-label randomized 
trial with 2900 participants to evaluate these two interventions versus standard care assigned in 
a 2:2:1 ratio, with 18 months of follow-up at three MSM-friendly research clinics in Kenya. Results 
will inform parameters to update a stochastic model of STI transmission and cost-effectiveness 
analysis to project the impact of scaled-up STI PPT and doxyPEP in Kenya. This work will provide 
the critical data needed to inform guidelines and improve STI control among this key population 
in sub-Saharan Africa and other resource-limited settings.  
Name 
Institution 
Susan M. Graham, MD MPH PhD 
University of Washington 
Eduard J. Sanders, MD MPH PhD 
Aurum Institute 
Joshua Kimani, MBChB MPH 
Partners for Health & Development in Africa 
Fredrick Otieno, DCMS MPH PhD Nyanza Reproductive Health Society 
Deven Hamilton, MPH MA PhD 
University of Washington 
R. Scott McClelland, MD MPH 
University of Washington 
Monisha Sharma, ScM PhD 
University of Washington 
Olusegun O. Soge, MSc PhD 
University of Washington 
Robert C. Bailey, MPH PhD 
University of Illinois at Chicago 
Connie Celum, MD MPH 
University of Washington 
Steven Goodreau, MA PhD 
University of Washington 

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4. Lay Summary 
1. Why should you do this study?  
We are conducting this study to test two different interventions to improve sexually 
transmitted infection (STI) control among gay, bisexual, and other men who have sex with 
men (GBMSM) in Kenya. GBMSM have a high burden of STI that mostly are detected by 
expensive laborotory tests that are not available in public hospitals. 
2. What questions are we trying to answer?   
One intervention that may reduce STIs among GBMSM is periodic presumptive treatment 
(PPT), in which one is treated every 3 months for STI regardless of symptoms. STI PPT has 
been recommended by the World Health Organization for GBMSM but never tested in a 
randomized trial. The other intervention is called doxyPEP, which consists of taking a 
medication called doxycycline 24-72 hours after you have condomless sex, as post-exposure 
prophylaxis (PEP) to prevent STI. DoxyPEP has been found to reduce STI among GBMSM in 
the United States and France but has not been tested among GBMSM in sub-Saharan Africa. 
No one knows if STI PPT or DoxyPEP is better at reducing STI among GBMSM in Kenya and 
similar settings. 
3. Where is the study taking place? 
In 3 friendly GBMSM study sites in Kisumu, Nairobi, and Mombasa.  
4. How many participants does it involve?  
We will enroll 2900 GBMSM participants. In addition up to 60 study staff will provide 
feedback on the two interventions. 
5. How will they be selected?  
GBMSM participants will be engaged and screened for eligibility at community-based 
organizations at each of the three study sites. Participants need to be between 18-29 years, 
report condomless anal intercourse with a man in the past 6 months, multiple partners or a 
partner with a STI. They need to be willing to follow study procedures and remain in the 
study area for 18 months. GBMSM will be excluded if they are unable to understand the 
study purpose and procedures despite a thorough explanation by and discussion with the 
study team, are allergic to any of the antibiotics used, have used antibiotics for 14 days or 
more in the month before enrolment, or are taking medications that impact any of the 
antibiotics used.  
6. What does the study involve for those taking part?  
Participants will be randomised to one of the following three groups: PPT, doxyPEP or 
standard of care. They will make seven quarterly research visits during the study, for 18 
months from enrolment.  
At each visit, a clinician will collect 2 throat swabs, 2 rectal swabs, urine, and blood from 
each participant. Blood will be tested for syphilis and, if there is an infection, participants will 
be treated according to standard of care as soon as results are available. The swab and urine 
samples will be tested for gonorrhea and chlamydia at the end of the study, to determine 
which intervention worked best to reduce STI. At each visit a small hair sample will also be 
collected to measure antibiotic use in all participants. 
AddiƟonally, a digital ﬁngerprint will be taken to allow us to conﬁrm parƟcipant’s idenƟty at 
study visits without using a name or other idenƟﬁers. We will also collect a brief survey 
lasƟng 50-60 minutes on a tablet computer. This survey will include quesƟons about sexual 
behavior, STI symptoms, anƟbioƟc use, substance use, and mental health. 
7. What are the risks and benefits of taking part?  

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There is a small risk of loss of privacy. For participants assigned to the intervention groups 
there is risk of medication side effects. Participants may benefit from regular physical exams, 
free syphilis testing, and counselling about STI prevention. 
8. How will the study benefit society?  
The burden of STI among GBMSM and their sexual partners in Kenya may be reduced 
through the outcomes of this study. This is a contribution to science and will help inform 
health policy for GBMSM in Kenya and similar resource-limited settings. 
9. When does the study start and finish?  
The study will likely start in the second half of 2024 and follow patients over 3 years 
(through June 2027), followed by testing of samples for chlamydia and gonorrhea and for 
antibiotic resistance in gonorrhea, as well as modeling and cost-effectiveness evaluations to 
inform scale-up, should either intervention prove to be more effective than standard care.   
5. Introduction/Background 
Bacterial sexually transmitted infections (STI) caused by Neisseria gonorrhoeae (NG), Chlamydia 
trachomatis (CT), and Treponema pallidum (syphilis) are highly prevalent and a major cause of 
morbidity among gay, bisexual, and other men who have sex with men (MSM) and their sexual 
partners. In sub-Saharan Africa (sSA), published prevalence estimates among MSM range from 
3.0%–11.5% for NG and 10.0%–14.5% for CT and 1.1%–5.7% for early syphilis. 1-7 Without timely 
screening and treatment, these STIs lead to a range of complications and increase HIV 
acquisition risk. 8 Indeed, modelling studies estimate that 10.2% of all HIV infections among 
MSM are attributable to NG and CT infections alone. 9 While laboratory-based or point-of-care 
(POC) nucleic acid amplification testing (NAAT) for NG and CT are widely used in well-resourced 
settings, 10,11 NAAT for NG and CT is prohibitively expensive in African settings, at approximately 
$97 per infection diagnosed, even if urethral, rectal, and pharyngeal samples are pooled. 1 As a 
result, most resource-limited settings rely on syndromic treatment, which misses over 90% of STI 
among MSM because they are asymptomatic. 2,12 
While development of low-cost POC diagnostics is an urgent priority, 12 low-cost and feasible 
interventions to control STI among MSM are needed now, as we await technology advances. In 
2011, the WHO recommended periodic presumptive treatment (PPT) to eradicate asymptomatic 
NG and CT infections for MSM who report condomless receptive anal intercourse (RAI) and 
either multiple sex partners or a sex partner with an STI in the past 6 months. 13 More recently, 
clinical trials among MSM in France and the United States have reported good safety and high 
adherence to doxycycline post-exposure prophylaxis (doxyPEP), which led to a 47%-70% 
reduction in NG, CT, and syphilis. 14-16 Evidence is lacking regarding acceptability, feasibility, 
safety, and effectiveness of PPT and of doxyPEP for MSM in settings such as sSA where the 
standard of care is syndromic treatment. These strategies each have potential drawbacks, such 
as increased antimicrobial resistance (AMR) in NG – a major public health concern globally. 17 
Research to evaluate the efficacy, long-term safety, impact on AMR, and cost-effectiveness of 
these STI control strategies among MSM in resource-limited settings is urgently needed. 18-20  
 
6. Problem Statement 
MSM face disproportionate risk for STIs, especially in resource-limited settings. A recent meta-
analysis of 2016 data estimated the global burden of bacterial STIs at 376.4 million infections, 
including 127.2 million chlamydia cases, 86.9 million gonorrhoea cases, and 6.3 million syphilis 
cases.1 The burden of STIs is greatest in low- and middle-income countries, and overlapping, 
synergistic epidemics of HIV and bacterial STIs in Africa have been recognized since the earliest 

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days of the HIV epidemic.1-3 Among MSM and their male sexual partners, STI caused by NG and 
CT are a significant cause of morbidity, ranging from urethritis, epididymitis and proctitis to 
disseminated gonococcal infection.4 Bacterial STI can also lead to reproductive health problems 
among cisgender female partners of MSM, including pelvic inflammatory disease, chronic pelvic 
pain, tubal infertility, pregnancy complications, and foetal and neonatal death.2,5-10 Of note, 56% 
of MSM in our ongoing cohorts report a cisgender female partner in the past 3 months 
(unpublished data). NG and CT increase the risk of HIV-1 transmission,11 with estimates from 
modelling studies suggesting that 10.2% of all HIV infections among MSM are attributable to NG 
and CT.12 In sSA, published prevalence estimates among MSM have ranged from 3.0%–11.5% for 
NG and 10.0%–14.5% for CT and 1.1%–5.7% for early syphilis.13-19  
Syndromic treatment, the current standard of care in Kenya, misses the majority of infections, 
but current diagnostic assays are too costly for most resource-limited settings. Syndromic 
treatment is standard care for STI management in most of sSA, is less costly than etiologic 
testing,3  and has relatively good sensitivity for male urethritis (87%-99%) and high cure rates 
when administered.20 Unfortunately, syndromic treatment misses over 90% of STIs among MSM 
because they are asymptomatic, especially rectal and pharyngeal infections.14,21 While 
laboratory-based or POC NAAT for NG and CT are widely used in well-resourced settings,22,23 
NAAT for NG and CT is prohibitively expensive in African settings, at approximately $19 per test 
conducted and $97 per infection diagnosed, even if urethral, rectal, and pharyngeal samples are 
pooled.13 In contrast, the estimated health expenditure per capita in Kenya in 2018 was $88.39.24 
The challenges with funding STI diagnostic tests is explicitly acknowledged in the 2022 WHO 
Implementation Tool for PrEP for HIV Infection, which recommends a stepwise approach to 
integration of STI services with PrEP services, starting with syndromic management and 
integrating rapid diagnostic tests and eventually molecular tests depending on resource 
availability, among other considerations.25 While the development of low-cost POC diagnostics is 
an urgent priority,21,26 low-cost and feasible interventions to control STI among MSM are needed 
now, as we await technology advances. 
DoxyPEP as an STI control strategy for MSM has been evaluated in well-resourced settings, but 
not in settings without access to periodic NAAT screening. The Intervention Préventive de 
l’Exposition aux Risques avec et pour les Gays (IPERGAY) sub-study, a randomized open-label 
clinical trial of doxycycline 200 mg within 24-72 hours after condomless sex (“doxyPEP”) among 
MSM in France, reported a good safety profile, high levels of adherence and a 47% relative 
reduction in new bacterial STIs among HIV pre-exposure prophylaxis (PrEP) users who also took 
200 mg of doxycycline following every sexual encounter.27 This reduction was driven by 
decreases in incident CT (70% reduction) and T. pallidum infections (73% reduction); there was 
no significant impact on NG.27 Since that time, the DoxyPEP study (PI Celum, NIH R01 AI143439), 
a randomized open-label trial among MSM and transgender women (TGW) people with HIV or 
taking HIV PrEP in Seattle and San Francisco randomized participants in a 2:1 ratio to 200 mg 
doxycycline hyclate within 72 hours of condomless sex or to a control arm, with STI testing at 
quarterly visits and when symptomatic.28 A single interim analysis after ~50% of follow-up time 
had accrued led to stopping of the control arm by an independent data and safety monitoring 
board. Among 360 participants on PrEP, 65 STI endpoints (29.5%) occurred in controls and 47 
(9.6%) in doxyPEP participants (RR 0.33; 95% confidence interval [CI] 0.23–0.47; p<0.0001). 
Among 194 participants with HIV, 30 STI endpoints (27.8%) occurred in controls and 31 (11.7%) 

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in doxyPEP participants (RR 0.42; 95% CI 0.25–0.75). NG, CT, and syphilis were each reduced in 
the doxyPEP arm, with only 8.1% of DoxyPEP participants having NG diagnoses, compared to 
19.8% in the control arm.28 More recently, the DOXYVAC study in France reported a significant 
reduction in all three STI (i.e., GC, CT, and syphilis) in the doxyPEP group with early termination 
of the control arm; these results will be presented at CROI 2023.29 The patient-controlled 
doxyPEP intervention could be effective in resource-limited settings, although the lack of 
quarterly NAAT to identify and treat “breakthrough” NG infections could limit effectiveness of 
this strategy. Because NG is the only STI that has been associated with increased HIV acquisition 
among MSM in Kenya,30 its effective control should be a priority. Further research to evaluate 
the overall risk-benefit ratio of doxyPEP, in terms of efficacy, long-term safety, impact on AMR, 
and cost-effectiveness among MSM in resource-limited settings is needed, especially as 
tetracycline resistance is common globally.31-34 
STI PPT has been proposed as a novel STI prevention strategy for MSM and TGW at risk for 
bacterial STI. In 2011, the WHO recommended PPT to eradicate asymptomatic NG and CT 
infections for MSM and TGW who report condomless RAI and either multiple sex partners or a 
sex partner with an STI in the past 6 months.4 Although targeting criteria for this 
recommendation have been evaluated by our research in Kenya,35,36 evidence of the efficacy of 
STI PPT is lacking, as is an evaluation of its potential downsides. Several studies on single-dose or 
monthly antibiotics among female sex workers in Asia and Africa demonstrated reduced disease 
burden using various PPT strategies.37-42 Moreover, a meta-analysis of PPT intervention effects 
showed a statistically significant impact on the incidence of curable STIs in 13 of 14 studies 
included.43 The premise that STI PPT could help reduce STI burden among MSM in resource-
limited settings is supported by this evidence, yet an investigation of the potential impact, risks 
and benefits of STI PPT for MSM and TGW in a randomized controlled trial has not been 
conducted. Since MSM are the larger population, and TGW may have different needs and 
perceptions of STI interventions than MSM, we focus on MSM in this application. As a provider-
delivered strategy that can be directly observed, STI PPT could prove more effective than doxyPEP 
if doxyPEP adherence is suboptimal or AMR limits the impact of doxyPEP on NG control. 
The potential emergence of AMR is an important concern for both doxyPEP and STI PPT. 
Following early studies of empiric single-dose antibiotics to reduce NG burden among female sex 
workers in the Philippines, some women (12%) reported self-prescribing antibiotics for empiric 
treatment, and high rates of penicillin-resistant NG were associated with self-prescription.44 
Today, multi-drug resistant NG is a growing international public health issue.45-50 In sSA, reports 
of cephalosporin resistance in NG have been relatively rare (<1%) to date; however, high levels 
of tetracycline and quinolone resistance have been reported, with detection of plasmid-
mediated tetracycline-resistant NG estimated at 73%–97%.45,46,51-53 In Kenya specifically, no 
confirmed cephalosporin resistance has been reported,45,54,55 although one study reported 
increasing minimum inhibitory concentrations for ceftriaxone in isolates collected between 2002 
and 2009.51 Of note, doxycycline resistance in NG is estimated at 56% in France,56,57 where 
doxyPEP had unclear efficacy against NG in the IPERGAY study, compared to 20%–30% in the US, 
where the doxyPEP study demonstrated a significant decrease in NG.28 Rigorous studies are 
needed to quantify the scope of potential resistance that might accompany doxyPEP or STI PPT in 
resource-limited settings with high levels of tetracycline resistance, to mitigate this critical 
problem.  

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STI control for African MSM: balancing benefits, risks, and costs. The potential benefits of 
implementing either doxyPEP or STI PPT for the control of CT, NG, and syphilis among MSM in 
African settings are substantial; at the same time, these strategies are untested, and potential 
risks – including adverse events, increased AMR, risk compensation impacting sexual behavior, 
and increased costs – could counteract these benefits. Only a well-designed randomized trial 
comparing these two interventions to standard care can help address these questions and 
determine whether the benefits outweigh risks for each strategy, compared to standard care.  
Experience conducting research on sexual health for MSM in Kenya. In the past 15 years, we 
have conducted numerous studies with MSM in coastal Kenya and Kisumu on sexual risk 
behavior,30,58-61 CT and NG prevalence and incidence,16,62 AMR,45 49 51 55 HIV incidence,30 partner 
notification services,63 risk factors for loss to follow up,64,65 PrEP uptake and adherence,59,66 ART 
adherence promotion,67-69 and mental health and substance use.70,71 72  In 2014, we formed a 
sexual and gender minority health research consortium with representatives from the three 
major population centers in Kenya (Kisumu, Nairobi and Mombasa) and designed a multi-site 
demonstration cohort study of HIV-negative MSM participants at high risk for HIV acquisition. 
This demonstration cohort was launched in 2019 with a small grant from the International AIDS 
Vaccine Initiative (IAVI) and programmatic funding from PEPFAR, successfully recruiting 850 
participants aged 18-29 years, 300 in Kisumu, 300 in Nairobi, and 250 in the Kenyan coast, for 
quarterly follow-up visits. Important features of this cohort include regular investigator 
meetings, common visit procedures, a common sociobehavioral questionnaire designed for 
audio computer-assisted self-interviewing (ACASI), and fingerprint scanning at each visit, with 
real-time checks of digital fingerprint data to prevent co-enrolment. X-pert CT/NG testing of 
urine, rectal, and pharyngeal specimens has been conducted among participants who remained 
in follow-up after the COVID-19 pandemic (approximately 67% of the pre-COVID-19 sample), 
demonstrating a combined CT/NG point prevalence of 17.3% at baseline and 15.0% at month 6. 
Retention in studies completed before the COVID-19 pandemic ranged from 82%‒94%,61,64,69 and 
is expected to be similar or higher in this trial, given adequate funding for rigorous retention 
support. 
Evaluation of the WHO PPT targeting criteria and number needed to treat at two sites in 
Kenya. In 2013, we assessed the prevalence of genitourinary and rectal symptoms among HIV-
negative and -positive MSM followed in the coastal Kenya cohorts, to estimate the number of 
men meeting WHO criteria for presumptive STI treatment, as well as the prevalence and 3-
month incidence of rectal NG and CT infections.35 Among 244 MSM screened, of whom 147 
(61.3%) reported any RAI in the past 6 months, 240 (98.4%) were asymptomatic. Among 85 
asymptomatic MSM meeting criteria for WHO-recommended STI PPT, 20 (23.5%) had rectal 
infections. Among 62 asymptomatic MSM who did not meet criteria, 7 (11.3%) had rectal 
infections. Sensitivity and specificity of the WHO algorithm were 74.1% (95% CI, 53.7%–88.9%) 
and 45.8% (95% CI, 36.7%–55.2%), respectively. Among MSM who would qualify for STI PPT, the 
number needed to treat (NNT) to treat one infection was four. In a 2016 follow-up study of MSM 
from the same coastal Kenya cohorts who reported RAI, the combined prevalence of rectal NG 
and CT by NAAT in 104 MSM was 21.2% at baseline. Over 6 months of follow-up, the combined 
incidence of rectal NG and CT was 53.0 (95% CI, 34.5–81.3) per 100 PY, with 12 cases of each for 
an incidence of 30.0 (95% CI, 17.2–53.3) per 100 PY for each infection.62  

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In 2016, among 698 MSM tested at baseline in the Anza Mapema study in Kisumu, overall 
anorectal NG/CT prevalence by NAAT was 5.2% (n=36), of which 58.3% (n=21) were 
asymptomatic infections.36 Factors associated with anorectal NG/CT in asymptomatic men were 
age 18-24 years (aOR 7.6, 95% CI 1.7–33.2, relative to older men), HIV-positive status (adjusted 
odds ratio [aOR] 6.9, 95% CI 2.2–21.6) and condomless anal sex in the past 3 months (aOR 3.8, 
95% CI 1.2–11.9). In a model-derived risk score developed to identify NG/CT cases in 
asymptomatic men, with 2 points each for age 18-24 and HIV-positive serostatus, and 1 point for 
any condomless anal sex in the past 3 months, sensitivity and specificity were optimal (81.0% 
and 66.1%, respectively) at a risk score cut-point ≥3, and the NNT was 12.36 
7. Justification for the study 
Feasible, scalable, cost-effective strategies to control bacterial STI among MSM in low-resource 
settings are urgently needed to reduce STI burden and decrease HIV transmission risk. STI PPT 
has been recommended by the WHO for MSM in settings in which NAAT are unavailable, and 
doxyPEP is a promising STI control strategy for MSM, yet there are no data on its health and 
economic impact relative to standard syndromic treatment in settings in which NAAT use is 
prohibitively expensive.  
We posit that there is equipoise to conduct a randomized trial, since while doxyPEP has 
demonstrated efficacy in studies of MSM in well-resourced settings in which NAAT-guided 
treatment are widely available, none of these studies was conducted in a resource-limited 
setting in which syndromic treatment is the norm. In addition, there have been no clinical trials 
of WHO-recommended STI PPT for MSM, which could have similar or greater efficacy, especially 
if doxycycline resistance in NG or poor adherence limit the efficacy of doxyPEP. Randomization 
in a 2:2:1 allocation with a common control arm will allow evaluation of both interventions in 
the same trial, and an open-label design allows for optimal evaluation of effectiveness and 
robust evaluation of acceptability, feasibility, and safety in practice, as well as adherence and 
sexual behaviour among participants who are aware of their assignment.   
8. Hypotheses  
Hypothesis 1: Both STI PPT and doxyPEP will decrease the burden of bacterial STI among Kenyan 
MSM, but doxyPEP will lead to more NG AMR than STI PPT, which may exert less pressure to select 
for mutations. 
Hypothesis 2: STI PPT and doxyPEP will each have high acceptability and feasibility among 
providers and patients, with minimal increases in adverse events relative to standard care.  
Hypothesis 3: Both interventions will lead to improved STI control in the target population relative 
to standard care, but STI PPT will be more cost-effective compared to doxyPEP. 
9. Objectives 
Objective 1. To evaluate the effectiveness and impact on AMR in NG of two interventions: WHO-
recommended PPT given every 3 months and doxy-PEP taken 24-72 hours after condomless sex, 
compared to standard syndromic treatment, for reducing STI burden among Kenyan MSM. 

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Objective 2. To assess the acceptability, feasibility, and safety of implementing WHO-
recommended PPT and doxy-PEP compared to standard care among providers and patients. 
Objective 3. To model the health and economic impact of scaling up WHO-recommended STI PPT 
and doxyPEP compared to standard of care on STI control among MSM and their partners in 
Kenya.  
10. Methodology 
a. Study sites 
Kisumu: The study will be conducted at the Anza Mapema clinic in Kisumu, which is presently 
serving MSM in research or prevention and care programmes. This site will be overseen by 
the Nyanza Reproductive Health Society and led by Dr. Fred Otieno. 
Nairobi: The study will be conducted at a Sex Worker Outreach Programme clinic in Nairobi, 
which is presently serving MSM and male sex workers. This site will be overseen by Partners 
for Health & Development in Africa and led by Dr. Joshua Kimani. 
Mombasa: The study will be conducted at the Pwani Research Centre at the Ganjoni 
Municipal Clinic site, in collaboration with two local community-based organisations (the HIV 
and AIDS People Alliance of Kenya [HAPA Kenya] and the International Centre for 
Reproductive Health [ICRH]) located in the Mombasa area. This site will be overseen by the 
University of Washington (UW) and led by Dr. Eduard Sanders, assisted by Dr. Scott 
McClelland, the lead researcher at Pwani Research Centre. 
b. Study design 
The proposed study is an open-label randomized controlled trial with a hybrid type 1 
implementation-effectiveness component comparing each intervention (i.e., STI PPT, 
doxyPEP) to a common control in a 2:2:1 ratio.  
Approach for objective 1: We will conduct an open-label randomized clinical trial with 2900 
participants to evaluate these two interventions versus the standard of care assigned in a 
2:2:1 ratio, with 18 months of follow-up and rigorous culture-based and molecular analysis 
of AMR in NG at three MSM-friendly research clinics in Kenya.  
Approach for objective 2: We will use multidisciplinary science to measure the acceptability, 
feasibility, and safety of these two interventions, using a conceptual model based on 
Proctor’s Implementation Science Framework. 21,22  
Approach for objective 3: Aim 1 and 2 results will inform parameters to update a stochastic 
model of STI transmission and cost-effectiveness analysis to project the impact of scaled-up 
STI PPT and doxyPEP in Kenya.  
c. Study populations 
Trial participants 
Inclusion criteria 

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1. 18-29 years old  
2. Assigned male sex at birth 
3. Identifies as male (cis-gender) 
4. Reports condomless anal intercourse with a man in the past 6 months 
5. Reports multiple male sex partners OR a male sex partner with a syndromic (urethritis, 
proctitis, or genital ulcer disease) or laboratory-diagnosed sexually transmitted infection 
in the past 6 months  
6. Willing and able to provide written informed consent and participate in all study 
procedures  
7. Planning to remain in the study area for 18 months  
Exclusion criteria 
1. Unable to understand the study purpose and procedures 
2. Allergy to cephalosporin (cefixime), macrolide (erythromycin or azithromycin), or 
tetracycline (doxycycline) class antibiotics 
3. Recent use of prolonged antibiotics (≥14-day course in the month before enrolment) 
Use of medications that impact cefixime, azithromycin, or doxycycline metabolism (check 
versus list in screening SOP) 
Study staff:  Research staff will participate in minuted staff meetings, provide feedback on the 
interventions tested, and contribute to the collection of data for cost analysis. 
Inclusion criteria 
1. 18 years of age or older 
2. Employed at one of the study sites as research staff contributing to this study 
Exclusion criteria 
1. None 
d. Sample size determination 
Power and sample size.  
The trial will have >80% power to detect a 33% reduction in a combined bacterial STI 
prevalence outcome, the optimal estimate of overall burden in a setting in which syndromic 
treatment is standard of care.  
We propose a standard randomized superiority design, comparing each intervention 
separately to the standard of care arm. The primary trial outcome will be the combined 
prevalence of NG, CT, and early syphilis ascertained by laboratory diagnosis (e.g., positive 
NAAT for NG or CT or new syphilis diagnosis, based on first positive rapid plasma reagin 
[RPR] or a fourfold increase in non-treponemal titres); the prevalence of each pathogen 
individually will be secondary outcomes. Outcomes will be assessed at baseline and every 3 
months for 18 months. We have selected prevalence instead of incidence as our outcome of 
interest, because a major drawback of syndromic treatment is its failure to identify and treat 
asymptomatic infections that can therefore persist as a reservoir for transmission, despite 
spontaneous clearance of some infections. 46 To detect a 33% reduction in STI prevalence 
(from 16.0% to 10.8%) for each intervention compared to standard care, we will need 2,465 

13 
Version 1.1, dated 10 June 2024  
 
participants total: 986 participants in each intervention group and 493 in the control group 
(α=0.05, β=0.20). Accounting for 15% attrition after randomization, we will need 2,900 
participants: 1,160 participants in each intervention group and 580 in the control group. We 
will target enrolment of ≈967 participants at each of our three research sites to attain the 
required sample size. For analysis of AMR rates, our power will be limited for very rare 
outcomes (e.g., cefixime resistance), but we will have 80% power to detect an increase in 
tetracycline resistance from 80% to 86.7% or from 85% to 90.8% in each intervention arm 
compared to the control arm. 
e. Stakeholder engagement and recruitment procedures 
Drs. Graham, Sanders, Otieno, and Kimani and their teams have a strong history of recruiting 
and retaining MSM in prospective studies. We will plan for multilevel engagement at each 
site during the protocol approval process, including input from our site-specific community 
advisory boards, local MSM community leaders, and NASCOP, building on strong existing 
relationships with these entities.  
Recruitment and retention. We will enrol 2900 MSM age 18-29 in this randomized 
controlled trial (1160 to each intervention arm and 580 in the control arm, with 
approximately 967 per site) and follow participants quarterly for 18 months.  
Our three research sites are in the three largest cities in Kenya (estimated populations 
4,400,000 in Nairobi, 1,440,000 in Mombasa, and 610,000 in Kisumu). We estimate that at 
least 2,000 MSM age 18-29 are active with the largest MSM community-based organization 
(CBO) in Mombasa (HAPA Kenya), and additional CBOs serving sexual minority men are in 
the study area. In Kisumu, NRHS serves approximately 2,000 MSM of whom 68% (1,340) are 
aged 18-29 years, and there are several vibrant CBOs serving MSM (MAAYGO, NYARWEK, 
etc.) in the study area. Finally, through the SWOP clinics, PHDA serves at least 7000 MSM, of 
whom approximately half are aged 18- 29. There are several active CBOs serving MSM in the 
Nairobi area, including HOYMAS, Ishtar, and GALCK+. 
Recruitment will be conducted by fliers, information sessions, word of mouth, and social 
media apps (Facebook, WhatsApp) to increase awareness of the study at the three research 
clinics and at local CBO partner sites in each site’s catchment area. In addition, we will 
recruit participants through experienced peer outreach workers affiliated with each site at 
previously mapped MSM hotspots, including bars, discos, restaurants, and social halls, and 
through moonlight outreaches. Recruitment will be done primarily through word of mouth 
and in-person outreach by our community outreach team to eligible participants in the study 
area, so as to minimize stigma surrounding male-male sex in Kenya. Any printed recruitment 
materials or flyers to be used on-site at our research clinic will be developed in collaboration 
with our CBO partners at each site and will be submitted to the IRB for review and approval 
before use. 
f. Study procedures 
A brief screening form will be used to evaluate whether an individual is eligible for study 
participation. This form will include a study ID that will be assigned sequentially at each site 
(KIS0001 for the first patient in Kisumu, etc.). For persons who do not enrol, we will collect 

14 
Version 1.1, dated 10 June 2024  
 
no identifiable information; data collection for these individuals will be limited to the 
screening form responses. For persons who enrol in the trial, the study ID will be matched to 
subject identifiers that will be collected after informed consent is given. 
Recruitment will begin in the second half of year 1, after a period of preparation involving 
staff hiring, training, and community engagement meetings. Participants will have their 
fingerprint scanned at enrolment and subsequent visits in a cloud-based database accessible 
to all three sites. Biometric identification allows for prevention of co-enrolment, as 
participation will be verified at each visit at each of the three sites. We have experience with 
fingerprint scanning from a previous study involving these 3 sites. Given our extensive 
experience recruiting MSM for a number of studies, assistance from our community 
partners, and ongoing work with the target population, we expect to meet this target with 
no problems. 
Retention efforts will be supported by ensuring that the trial sites offer high-quality MSM-
friendly services, offer flexible hours, monitor clinic flow and wait times, and provide HIV 
and STI treatment free of charge. In addition, we use SMS reminders 3 days and 1 day before 
a scheduled visit to promote timeline attendance. Tracing of participants who miss visits will 
be the responsibility of the outreach teams at each research site. These teams have many 
years’ experience tracing patients who miss visits or have laboratory results needing follow-
up. Because residential locations are very difficult to find due to poor maps and the lack of a 
formal numbering system, the team has used GPS mapping to locate a participant’s home or 
workplace for future contacts; this service is provided to participants who agree to show the 
home or workplace to the study team member after a clinic visit. In addition, we collect 
tracking information that includes participant cell phone numbers, home location and 
nearby landmarks. The outreach team will use SMS reminders before visits, cell phone calls 
in the event of missed visits, and home visits as needed to encourage retention and 
complete follow-up. These methods have led to successful retention of ≈85% participants on 
average in completed trials we have conducted and will be bolstered for this trial. 
Regardless of the participant retention methods described above, participants may 
voluntarily withdraw from the study for any reason at any time. Should a participant indicate 
that he would like to withdraw, study staff will request completion of a short assessment 
survey characterizing reasons for withdrawal. The MPIs may withdraw participants from the 
study in order to protect their safety and/or if they are unwilling or unable to comply with 
required study procedures, after consultation with rest of the research team. Participants 
also may be withdrawn if the study sponsor, government or regulatory authorities, or 
IRBs/ECs terminate the study prior to its planned end date. Trial participants who decide to 
withdraw from the study prior to the last follow-up visit will be asked if they will complete 
the procedures that would have been completed at this visit, but they will not be required to 
do so. Additionally, study staff will invite such participants for brief exit interviews and 
record the reason(s) for all withdrawals from the study in participants’ study records 
(regardless of whether participants complete an exit interview), to further understand 
reasons for withdrawal. The brief exit interviews will be recorded if the participant consents 
to this. 

15 
Version 1.1, dated 10 June 2024  
 
Population and procedures (Table 1, Figure 1). Interested individuals will be provided 
information on the study intervention and randomization, then screened for eligibility. 
Sociodemographic data will be collected for all individuals screened, whether or not they are 
determined eligible or choose to enrol. Those who are eligible and choose to enrol will 
provide written informed consent.  
 
Subjects will then be randomized in variable-sized blocks stratified by site, using opaque 
envelopes opened at randomization. Participants will attend quarterly visits, which are 
standard of care for HIV prevention and care services, for 18 months of follow-up. At each 
visit, we will collect participant data via Audio Computer-Assisted Self Interview (ACASI) 
software (Questionnaire Development System™, Nova Research Company, Silver Springs, 
MD, USA) that we have used for 
many of our studies in Kenya. Clinic 
data will be entered in REDCap, a 
secure web application for building 
and managing online surveys and 
databases which is freely available 
through the UW or in Computer 
Assisted Personal Interview (CAPI) 
software (Questionnaire 
Development System™, Nova 
Research Company, Silver Springs, 
MD, USA).  
Study arms. The three medications 
to be used in the interventions we 
propose have been used safely for 
STI treatment for decades. In 
addition, doxyPEP has not led to 
significant safety concerns in the 
two trials with available results to 
date. 15,23 All study medications will 
be obtained from a quality-
controlled pharmacy used by the 
ongoing Kenya “dPEP” trial of 
doxyPEP for adolescent girls and 
young women (MPI Bukusi and 
Baeten, R01 AI145971): Goodman 
Agencies, Limited in Nairobi. Our study arms will be as follows: 

16 
Version 1.1, dated 10 June 2024  
 
• 
STI PPT intervention. Participants assigned to the STI PPT arm will be evaluated at 
baseline and every 3 months thereafter for STI PPT eligibility based on having had 
condomless anal sex and either multiple sex partners or a sex partner with an STI in the 
past 6 months. 24 If eligible, they will be offered 400 mg po cefixime plus 1 gram 
azithromycin po under direct observation, using the same regimen as for syndromic 
treatment per the latest WHO recommendations. 25 
• 
DoxyPEP intervention. Participants assigned to the doxyPEP arm will be provided with a 
30-day supply of doxycycline hyclate at each quarterly visit and given 1:1 counselling on 
the self-administration of 200 mg po doxycycline within 24-72 hours after condomless 
anal or vaginal sex as frequently as daily if indicated but not more than once daily, in 
accordance with the doxyPEP trial in the United States. 15 Refills will be provided as 
needed. Since doxyPEP is only indicated after condomless sex, some participants will use 
this less than daily and so will not need monthly refills. We will instruct participants very 
clearly that no more than two 100-mg tablets should be taken on a given day, to avoid 
overuse. When refills are needed, participants will have the option to pick these up at 
the clinic where they are enrolled or to request delivery from an outreach worker 
trained by the study team. Participants will not be reimbursed for refill pick-up at the 
clinic, since we assume those who come for these refills will be attending the clinic for 
other purposes (e.g., social activities, other events at the site). Refill provision will be 
carefully documented at the clinic and when delivery is provided in the field by outreach 
workers. 
• 
Standard care. Participants assigned to the standard care arm will receive screening for 
STI symptoms at every scheduled visit and syndromic treatment with cefixime 400 mg 
po stat plus azithromycin 1 gram po stat under direct observation, in accordance with 
current Kenyan recommendations for genital and anorectal infections. 26 This regimen 
will be updated if Kenyan recommendations change. Standard care also includes 
notification of partners who may have been exposed, with expedited partner treatment 
to those in ongoing relationships with the index patient.26 
Participants may return to the study clinic for interim visits at any time STI symptoms are 
present, regardless of study arm. Intervention participants who report genitourinary or 
rectal symptoms compatible with urethritis or proctitis at scheduled visits will also receive 
syndromic treatment. All treatment will be documented, whether at a scheduled quarterly 
or interim visit. Fidelity of delivery of each intervention will be closely monitored and 
documented, using a detailed implementation SOP with a checklist of steps completed.  
Procedures at study visits. At each quarterly study visit beginning with the enrolment visit, 
the following procedures will be carried out: 
• 
Before each scheduled study visit, we will contact participants by SMS with a visit 
reminder. If participants miss a scheduled visit, we will contact them by phone or SMS 
asking them to reschedule. If we cannot reach them, we will send a peer education 
worker to find them at the address provided to us upon enrolment. 
• 
At each scheduled visit, participants will be asked to complete a brief survey lasting 30-
45 minutes on a tablet computer with questions about their sexual behaviour, STI 
symptoms, antibiotic use, substance use, and mental health since the last visit. 
• 
At each scheduled visit, participants will see a clinician, who will do the following: 

17 
Version 1.1, dated 10 June 2024  
 
o Ask if the participant has any symptoms of an STI, such as pain or discharge with 
urination, throat pain, rectal pain or discharge, genital lesions, or a rash. 
o Perform a focused physical examination depending on the participant’s 
symptoms. 
o Ask if the participant has any side effects that can be associated with taking 
cefixime, azithromycin, or doxycycline. 
o Collect two swabs of the participant’s throat, two swabs of their rectum, and a 
small sample of hair (approximately 20 hairs from the back of the head). 
o Ask the participant to provide a urine sample.  
o Draw the participant’s blood, collecting 1 tube of blood for syphilis testing. 
o Provide treatment according to Kenyan guidelines for any STI symptoms the 
participant has (part of standard care). 
o Provide HIV testing and prevention services if the participant is HIV negative and 
HIV care if the participant is HIV positive, according to Kenyan guidelines (part of 
standard care). 
o Offer the participant condoms, lubricants and counseling about how to reduce 
their STI risk. 
o Give the participant a survey asking their opinion about the STI control 
intervention they are assigned to.  
• 
If a participant has STI symptoms between scheduled visits, such as a sore throat, 
discharge from their penis, burning when they urinate, or rectal pain or discharge, they 
will be asked to come to the research site for sample collection to test for possible STI. 
• 
If a participant’s blood test is positive for syphilis, they will be contacted so they can 
come to the clinic and receive treatment. 
• 
After each scheduled research visit, participants will receive 1000 Kenya shillings 
(approximately $7.00) to compensate for their time and participation. This is in line with 
our most recent research studies with this population in Kenya. 
• 
Text reminders will be sent for scheduled study visits and exit interviews. Participants 
who miss a scheduled visit or exit interview, and those with lab results indicating a need 
for syphilis treatment, will be traced and invited to return to the clinic where they 
enrolled.  
• 
Participants who move to a different study site (e.g., from Nairobi to Kisumu) will have 
the option to complete follow-up at the new location. Those who are unable to 
complete participation will be invited to an exit interview for their feedback before 
being withdrawn from the study. 
Timing of study visits and procedures: 
• 
The initial enrolment visit will take approximately 90 minutes. 
• 
Scheduled follow-up visits every 3 months will take approximately 60 minutes. 
• 
Interim visits for symptom evaluation or for treatment of syphilis, when needed, will 
take approximately 30 minutes. 
Study medications 
All study medications will be obtained from a quality-controlled pharmacy used by the ongoing 
Kenya dPEP trial of doxyPEP for adolescent girls and young women (MPI Bukusi and Baeten, R01 
AI145971): Goodman Agencies or a quality-controlled pharmacy with similar degree of quality 

18 
Version 1.1, dated 10 June 2024  
 
assurance and oversight. A licensed clinical trials pharmacist will provide oversight to pharmacy 
technicians based at each site. As described above, our study arms will be as follows: 
• 
STI PPT intervention. Participants assigned to the STI PPT arm will be evaluated at 
baseline and every 3 months thereafter for STI PPT eligibility based on having had 
condomless anal sex and either multiple sex partners or a sex partner with an STI in the 
past 6 months. 24 If eligible, they will be offered 400 mg po cefixime plus 1 gram 
azithromycin po under direct observation, using the same regimen as for syndromic 
treatment per the latest WHO recommendations. 25 
• 
DoxyPEP intervention. Participants assigned to the doxyPEP arm will be provided with a 
30-day supply of doxycycline hyclate at each quarterly visit and given 1:1 counseling on 
the self-administration of 200 mg po doxycycline within 24-72 hours after condomless 
anal or vaginal sex as frequently as daily if indicated but not more than once daily, in 
accordance with the doxyPEP trial in the United States. 15 
• 
Standard care. Participants assigned to the standard care arm will receive screening for 
STI symptoms at every scheduled visit and syndromic treatment with cefixime 400 mg po 
stat plus azithromycin 1 gram po stat under direct observation, in accordance with current 
Kenyan recommendations for genital and anorectal infections. 26 This regimen will be 
updated if Kenyan recommendations change. 
Specimens, Testing and Shipment within and outside Kenya: 
As described above in the procedures section, the following specimens will be subject to 
shipment: 
• 
All NG/CT samples for NAAT. These samples will be transferred (from Ganjoni Clinic) or 
shipped (from Kisumu or Nairobi) for storage at -80⁰C in the UW/University of Nairobi East 
Africa STI Laboratory in Mombasa, which has operated with external quality assurance for 
>10 years. At the end of study follow-up, Aptima Combo 2 testing for NG and CT will be 
conducted in Mombasa on a Hologic Panther platform by experienced laboratory staff 
blinded to randomization assignment. To reduce testing costs, we will pool the 3 samples 
from each participant for initial testing following published protocols. 28,29 All NG-positive 
pools will be broken down and individually tested to identify the infected site or sites. 28  
• 
NG AMR testing in Seattle. We will perform culture and susceptibility testing of urethral 
swabs from symptomatic urethritis cases in Kenya, due to the high yield of these specimens 
on culture. 34 We will supplement this testing with rigorous molecular methods using 
residual NAAT samples and non-cultured swab or urine specimens to identify well-
characterized genetic AMR determinants conferring cefixime, azithromycin or tetracycline 
resistance in NG. Of note, we have validated and successfully used these methods for strain 
typing and characterization of resistance determinants in NG. 33,35,36 We will select a random 
sample of 25% of all NG-positive specimens (≈761 samples) from each intervention arm 
(50% at baseline and 50% at follow-up) for shipment to the laboratory of Dr. Soge at the UW 
for molecular testing. Of note, Dr. Soge has begun a collaboration to transfer this technology 
to the UW/University of Nairobi East Africa STI Laboratory at the Coast General Hospital in 
Mombasa, which will be used as our primary AMR testing site once capacity is fully 
established and rigorous quality control and quality assurance measures are in place. 

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Version 1.1, dated 10 June 2024  
 
• 
Hair samples for doxycycline levels. We will collect hair samples from all participants at all 
visits, but do not have enough in the budget to test them all. Therefore, we plan to ship a 
random sample of 10% of all hair samples collected (≈812 samples) from the month 6 and 
month 18 visits in the doxyPEP arm to the UW in Seattle for testing for doxycycline levels; 30 
this testing will be done through the Hair Analytical Lab at UCSF or another vendor, 
depending on costs and availability at the time of testing. The rest of the samples will be 
stored and if funding permits and the science warrants it, we might test additional samples. 
Specimen collection, testing and storage. HIV testing and counseling will be conducted for 
previously HIV-negative participants at each quarterly visit, per Kenyan guidelines for key 
populations. At each quarterly visit, participants will undergo hair collection for testing of 
doxycycline levels and three-site screening for NG and CT, with provider-collected pharyngeal 
and rectal swabs (2 of each) and a clean-catch urine. Participants who return to the study clinic 
for interim STI symptoms will undergo collection of the same pharyngeal, rectal, and urine 
samples. We will not diagnose and treat infections other than syphilis in real time. Syphilis 
serology including RPR (Becton Dickinson) and, if reactive, TPHA (Biotec) will be tested at 
quarterly visits, with treatment provided to participants with a new syphilis diagnosis as soon as 
results are available. Samples for NG and CT NAAT will be stored for batch testing at the study’s 
end. Participants who have symptomatic urethritis at any study visit (estimated at 5% of visits or 
≈1,015 visits) will undergo swab collection of urethral discharge for Gram staining and NG 
culture using modified Thayer-Martin Agar, a selective medium supplemented with nystatin, 
colistin, vancomycin, and trimethoprim that favours growth of Neisseria gonorrhoeae while 
suppressing genital and extragenital commensal microbial flora growth. Antimicrobial 
susceptibility testing (AST) will be performed using disk diffusion for penicillin and tetracycline 
and Etest for cefixime, azithromycin, and doxycycline, using WHO control strains for quality 
assurance of AST at each of the site’s microbiology labs. 27  
All NG/CT samples for NAAT will be transferred (from Ganjoni Clinic) or shipped (from Kisumu or 
Nairobi) for storage at -80⁰C in the UW/University of Nairobi East Africa STI Laboratory in 
Mombasa, which has operated with external quality assurance for >10 years. At the end of study 
follow-up, Aptima Combo 2 testing for NG and CT will be conducted on a Hologic Panther 
platform by experienced laboratory staff blinded to randomization assignment. To reduce 
testing costs, we will pool the 3 samples from each participant for initial testing following 
published protocols. 28,29 All NG-positive pools will be broken down and individually tested to 
identify the infected site or sites. 28 All NG, CT, and early syphilis diagnoses will be reviewed by 
an Endpoint Adjudication Committee blinded to treatment arm. We will collect hair samples 
from all participants at all visits, but do not have enough in the budget to test them all. 
Therefore, we plan to ship a random sample of 10% of all hair samples collected (≈812 samples) 
from the month 6 and month 18 visits in the doxyPEP arm to Seattle for testing for doxycycline 
levels; 30 this testing will be done through the Hair Analytical Lab at UCSF or another vendor, 
depending on costs and availability at the time of testing. The rest of the samples will be stored 
and if funding permits and the science warrants it, we might test additional samples. 
NG AMR testing in Seattle. The potential for selection of AMR by STI PPT or doxyPEP is one of 
the greatest risks to the success of these strategies; however, the magnitude of this risk cannot 
be known without empiric data. Cephalosporin resistance in N. gonorrhoeae is happily still rare 
in Kenya. Azithromycin resistance in N. gonorrhoeae is uncommon in Kenya (0%-8.3% in recent 

20 
Version 1.1, dated 10 June 2024  
 
studies), 31,32 and STI PPT may not increase it substantially given co-coverage with cefixime. 
Resistance to azithromycin in C. trachomatis has not been seen. Plasma-mediated doxycycline 
resistance in NG is common and may impact the efficacy of doxyPEP. 33 We will perform culture 
and susceptibility testing of urethral swabs from symptomatic urethritis cases due to the high 
yield of these specimens on culture, 34 but will supplement this testing with rigorous molecular 
methods using residual NAAT samples and non-cultured swab or urine specimens to identify 
well-characterized genetic AMR determinants conferring cefixime, azithromycin or tetracycline 
resistance in NG. Of note, we have validated and successfully used these methods for strain 
typing and characterization of resistance determinants in NG. 33,35,36 We will select a random 
sample of 25% of all NG-positive specimens (≈761 samples) from each intervention arm (50% at 
baseline and 50% at follow-up) for shipment to the laboratory of Dr. Soge at UW for molecular 
testing. DNA will be purified and extracted from residual NAAT samples, swabs, and/or urine 
using the Total Nucleic Acid Isolation Kit on the Roche MagNA Pure 24 System (Roche 
Diagnostics, Indianapolis, IN), an automated nucleic acid purification system that has been 
validated by Soge Lab to yield high-quality DNA from NAAT and clinical specimens. 37 Molecular 
characterization of NG will include strain typing using the internationally used N. gonorrhoeae 
multiantigen sequencing typing (NG-MAST) system; 38 detection of plasmid-mediated tet(M), 
which confers high-level tetracycline resistance (tetR), and the chromosomally-mediated 
mutation rpsJ V57M, which confers low-level tetR; 39 detection of single-nucleotide 
polymorphisms (SNPs) associated with reduced cephalosporin (cefixime/ceftriaxone) 
susceptibility and resistance (mosaic penA alleles, penA A311V, penA N513Y, ponA L421P, mtrR 
−35delA, and porB G120K/A121D/N), 40-43 and detection of azithromycin resistance (23S rRNA 
A2059G, C2611T) 41,44 by PCR and sequencing. Well-characterized positive control strains and 
negative controls will be included in all PCR assays. 45 Of note, Dr. Soge has begun a collaboration 
to transfer this technology to the UW/University of Nairobi East Africa STI Laboratory at the 
Coast General Hospital in Mombasa, which will be used as our primary AMR testing site once 
capacity is fully established and rigorous quality control and quality assurance measures are in 
place. 
Aim 2. To assess the acceptability, feasibility, and safety of implementing WHO-recommended 
STI PPT and doxy-PEP compared to standard care among providers and patients. Approach: We 
will use multidisciplinary science to measure acceptability, feasibility, and safety of these 
interventions, using a conceptual model based on Proctor’s Implementation Science 
Framework21,22 (Figure 2, with primary outcomes related to each aim in bold italic.)  
Considering the 
unique needs of 
Kenyan MSM with 
respect to sexual 
health will be 
essential to 
developing 
effective 
strategies to 
address their STI 
burden. In addition, any STI control intervention must be acceptable, feasible, and safe for the 

21 
Version 1.1, dated 10 June 2024  
 
patient. We will prioritize these three outcomes for our Aim 2 work and capture acceptability 
and feasibility data from both providers and participants. We note that Aim 1 will focus on two 
service outcomes (effectiveness, AMR rates) and Aim 3 will include analysis of an 
implementation outcome (costs). Secondary outcomes related to the STI PPT and doxyPEP 
interventions that we will assess include the implementation outcomes of uptake and adherence 
(related to acceptability and sustainability of the interventions) and client outcomes including 
satisfaction, symptoms, and sexual behaviour. The quantitative and qualitative measures we will 
use to assess these outcomes are presented in Table 2. 22 
 
Data collection. Due to its enhanced privacy, ACASI will be the main method of data collection, in 
English, Dholuo, or Kiswahili. We have successfully used ACASI to capture data in multiple projects 
at our research sites. 48-52 Because participants occasionally have difficulties using ACASI, a 
research assistant will be available to assist participants if needed. Our initial selection of 
measures to evaluate draws from our conceptual model for the Aim 2 work, extensive experience 
conducting research among Kenyan MSM and published literature on correlates of sexual 
behaviour, HIV/STI incidence, and medication adherence. Table 3 presents an overview of data 
elements, content, tools for assessment, frequency of assessment, and applicable study arm. Of 
note, this list will be updated and finalized before study launch.  
 
Table 3. Quantitative Data Elements Collected from Participants: Content, Collection Method, Frequency and Arm 
Data Element 
Method and Content 
Frequency and Arm 
Aim 1 Outcome Variables 
NG, CT, or early 
infection (primary 
outcome) 
Aptima NAAT: Pooled specimen (throat, rectal, and urine) 
positive for NG or CT; first positive rapid plasma reagin [RPR] 
or a fourfold increase in non-treponemal titres) for early 
syphilis 
All arms: Quarterly and 
at interim visits for STI 
symptoms 
Each infection 
individually 
Same as above 
All arms: Quarterly and 
at interim visits for STI 
symptoms 
AMR 
Resistance to penicillin, tetracycline, cefixime, azithromycin, or 
doxycycline by culture of urethral discharge (symptomatic 
urethritis cases) or molecular testing (25% of all NG-positive 
samples 
All arms: Quarterly and 
at interim visits for STI 
symptoms 
Aim 2 Outcome Variables 
Acceptability 
ACASI: Acceptability of Intervention Measure (AIM), 53 Likert-
scale questions on each intervention adapted from the 
Intervention arms: 
Quarterly 

22 
Version 1.1, dated 10 June 2024  
 
doxyPEP study15 
Feasibility 
ACASI: Feasibility of Intervention Measure (FIM) 53  
Intervention arms: 
Quarterly 
Uptake 
Direct observation: Administration of cefixime and 
azithromycin, receipt of doxycycline 
Intervention arms: 
Quarterly 
Adherence 
ACASI: Self-report questions on interventions adapted from 
the doxyPEP study; 15 counts of returned doxycycline tablets; 
hair doxycycline levels; directly observed PPT 
Intervention arms: 
Quarterly 
Safety including 
social harms 
ACASI questions plus study monitoring: adverse events and 
social harms reported by participants or study staff 
All arms: Quarterly 
 
Symptoms 
ACASI: Modified SAFTEE scale: 26-item scale rating symptoms 
and their attribution to medications; 54 pharyngeal, urethral, or 
rectal symptoms since past visit and whether treatment was 
sought outside the study 
All arms: Quarterly 
Sexual risk behaviour 
ACASI: Condomless anal sex, anal intercourse, vaginal 
intercourse, condom use, partner numbers, partner HIV status, 
concurrency, sexual networks, sexual violence 
All arms: Quarterly 
PrEP or ART use and 
adherence 
ACASI: Use of PrEP (if HIV-negative) or ART (if HIV-positive), 
visual analog scale, 55,56 self-rating scale, 57 pill counts, 58 
medication possession ratio59 
All arms: Quarterly 
Study retention 
Study records: Scheduled visits completed within 1-month 
window 
All arms: Quarterly 
Potential Correlates of Study Outcomes 
Demographics 
ACASI: Age, education, religion, marital status, gender identity, 
60 sexual orientation, transactional sex, employment, income 
Both arms: Baseline 
Clinic access 
ACASI: Transportation costs, wait times, problems with clinic 
hours or staffing, experienced discrimination61 
Both arms: Quarterly 
STI knowledge 
ACASI: Questions will be based on ongoing work in the 
Shauriana project (R34 MH118950-01) 
Both arms: Quarterly 
STI risk perception 
ACASI: Two questions “What do you think is your risk of 
getting (giving) STIs from (to) your partner?” (4 item Likert 
scale) 62,63 
Both arms: Quarterly 
HIV status 
Laboratory testing according to Kenyan guidelines at each 
study visit, with quarterly rapid tests if previously seronegative 
and every 6 month viral load monitoring if seropositive64 
Both arms: Quarterly or 
every 6 months, 
depending on HIV status 
Antibiotic use 
ACASI: Trimethoprim-sulfamethoxazole prophylaxis, 33 report 
of any antibiotic use outside the study in the past 30 days 
Both arms: Quarterly 
Substance use 
ACASI: Alcohol Use Disorders Identification Test (AUDIT), 65-67 
Drug Abuse Screening Test (DAST) 68 
Both arms: Quarterly 
Sexual stigma 
ACASI: Sexual stigma as used in our previous work. 69  
Both arms: Every 6 
months 
HIV stigma 
HIV/AIDS Stigma Instrument – PLWH70 
Both arms: Every 6 
months if HIV positive 
Depressive 
symptoms 
ACASI: Patient Health Questionnaire-9 (PHQ-9): a validated 
Swahili version is available. 71,72 
Both arms: Quarterly 
Qualitative Data Collection. During study screening, a brief questionnaire with 2-3 open-ended 
questions will be used to capture reasons for declining to enrol, including poor individual-level 
acceptability of STI PPT, doxyPEP or randomization. During the trial, qualitative data collection will 
include brief exit interviews with a subset of 30 participants in each intervention arm (10 at each 
site), to understand participant-level acceptability and satisfaction with the interventions. 
Interviews will be conducted using participants’ preferred language (English, Dholuo, or Kiswahili). 
Participants will be sampled for these interviews to include a range of ages and reported risk 

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behaviours (e.g., transactional sex), using a stratified-purposive sampling approach. At any visit on 
which a participant withdraws, a similar exit interview will be conducted to obtain feedback on 
the intervention received. Interviews will be recorded if permission is granted; detailed notes will 
also be taken to document participant feedback. Minutes will be taken at monthly staff meetings 
at each site to document any challenges arising. At each staff meeting, we will let staff know that 
we are taking notes for the research and that staff can let us know if they have any questions or 
concerns about this. At the end of the study, acceptability and feasibility for providers will also be 
assessed using the 4-item AIM and 4-item FIM tools in a questionnaire administered to research 
staff. 53 Examples of AIM items tailored for the STI PPT intervention include: “STI PPT meets my 
approval” and “STI PPT is appealing to me.” Example of FIM items tailored for the doxyPEP 
intervention include “DoxyPEP seems implementable” and “DoxyPEP seems easy to use.” 
Responses include 1 = completely disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, 
and 5 = completely agree. 
Microcosting. We will conduct microcosting, semi-structured interviews or focus group 
discussions with staff regarding time spent on different work activities, and time and motion 
observation of the intervention and standard of care treatments within the RCT. Costs will be 
divided into diagnostic evaluation or testing and NG and CT treatment. Direct medical costs of 
standard syndromic treatment, STI PPT, and doxyPEP will include costs of personnel, 
transportation, and communication. Direct medical costs of NAAT-guided treatment will include 
these costs, plus the costs of testing supplies, which are a factor of resource use for testing and 
unit costs for NAAT supplies. Costs of personnel are a factor of wages for clinical, counselling, 
field workers, and laboratory testing (NAAT scenario only), and the time spent performing 
different activities. Communication cost will be obtained by estimating the number of minutes 
per call, the mean number of calls, and costs per call-minute. Costs of NG and CT treatment 
include the costs of medications used for treatment and the cost of partner treatment under 
each scenario. Indirect costs will be estimated using data from patient exit interviews and 
publicly available data. Questions about patient transport costs, transport time, and upkeep 
costs will be added to data collection forms and subsequently combined with data on patient 
waiting and patient contact time with health workers to estimate indirect costs. Wages will be 
estimated based on Kenya’s gross domestic product per capita. We will conduct semi-structured 
interviews or focus group discussions with up to 5 research staff at each site, to assess daily 
responsibilities associated with the interventions and standard syndromic treatment. Time and 
motion observation of intervention activities for 50 patient/provider interactions per 
intervention arm will be conducted to inform staff time costs and productivity assumptions. 
Research time (e.g., informed consent) will be removed from programmatic costs. These 
procedures will also be used to elicit qualitative information from staff on the feasibility of 
intervention delivery. If staff agree, these sessions will be audio-recorded for ease of analysing 
the data. Participants present during time and motion observation will not be audio-recorded 
without participants’ verbal agreement.  
g. Limitations and Alternative Approaches 
We have carefully considered our study design and approach to optimize feasibility, while 
maintaining high rigor and ensuring that results will be reproducible. 

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Feasibility. Kenya is an ideal setting for evaluating STI PPT and doxyPEP among MSM, as the 
Government of Kenya’s visionary 20-year plan for evidence-based HIV and STI prevention, the 
Kenya HIV Prevention Revolution Road Map: Count Down to 2030, aims to drive new HIV 
infections towards zero between 2013 and 2030 using effective HIV and STI prevention 
initiatives. 83 As HIV transmission decreases, risk has become more concentrated in key 
populations such as MSM, who also experience high rates of bacterial STI. The Kenyan Ministry 
of Health endorses STI control in key populations, has worked to address health disparities 
among MSM, and supports this proposal, ensuring that our trial results will be linked to policy. In 
addition, each research site has collaborative relationships with MSM-led community-based 
organizations with large membership rosters, laying the groundwork for community feedback on 
the proposed work and its implementation, and for successful outreach, recruitment, and 
retention. 
PPT regimen selection. We debated using the CDC’s currently recommended STI treatment 
regimen consisting of IM ceftriaxone and PO doxycycline. However, we decided against this 
because of concerns about low acceptability of injections and the advice of Dr. Teodora Wi, the 
WHO Medical Officer in charge of STI Programs. Most low- and middle-income countries still 
using cefixime and azithromycin have not seen the same levels of AMR as in high-income 
countries, likely due in large part to lack of NAAT screening to guide treatment. 84,85 Azithromycin 
provides both CT coverage and dual coverage of most NG. Although azithromycin resistance can 
emerge in NG due to the long half-life of this drug, 86,87 data from the CDC’s NG surveillance 
program suggest that cefixime resistance decreased after the addition of azithromycin to the NG 
treatment regimen. 88,89 In contrast, a recent study of our isolates in Kenya suggested that 
doxycycline can select for plasmid-mediated penicillin resistance and therefore could potentially 
increase the risk of cephalosporin resistance. 31 Therefore it is critical to evaluate NG AMR to all 
three antibiotics in all study arms. 
Timing of STI PPT administration. The WHO did not specify a frequency for STI PPT assessment 
and delivery in their recommendations. 13 We debated offering this intervention on a 6-monthly 
basis, but felt this might weaken the intervention’s efficacy. We will be able to explore the 
potential efficacy of different frequencies of PPT administration in our modelling work. 
Treatment of uninfected individuals. We have estimated a NNT with STI PPT to treat one 
infection ranging from 4-12 (Preliminary Results). In the doxyPEP study in United States settings 
with similar STI incidence as in Kenya, the NNT was estimated at 5. 15 Treatment of uninfected 
individuals occurs in the setting of epidemiologic treatment of partners; for example, a recent 
study estimated that 65% of individuals receiving expedited partner treatment (often with po 
cefixime) are asymptomatic and NAAT negative. 90 An important aspect of the proposed research 
is delivery of STI PPT or doxyPEP in a setting in which the vast majority of bacterial STI are 
currently undiagnosed and therefore left untreated. 
Low STI rates in the control condition. Given high rates of STIs in our MSM cohorts and service 
disruptions that resulted from COVID-19, it is unlikely that STI rates will be low. Our data safety 
and monitoring board will monitor STI rates in the control condition and on STI treatment 
received outside the research clinics and will inform the team if assumptions regarding STI rates 
should be revisited to ensure adequate power. 

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Selection bias: This study depends on participation by MSM who live in the catchment areas of 
the three research clinics, accept research screening, and agree to enrol in the study. As detailed 
in the approach, we will collect data on characteristics of the MSM who decline trial 
participation.  
Generalizability. While the three research sites selected do not represent all geographic areas 
and CT/NG prevalence conditions in Kenya, data from the MHRC suggests that the behaviour risk 
profiles, sexual networks, and social interactions of MSM across the three sites are similar. 
Evaluating these interventions at sites with adequate research capacity is important for practical 
reasons related to feasibility, budget, and experience.  
Contamination and period effects: We will collect data on receipt of syndromic treatment and of 
other antibiotics in the past 30 days during follow-up, to monitor for contamination in the 
standard care arm. Providing STI PPT or doxyPEP to intervention arm participants may reduce STI 
rates in the control arms by reducing NG and CT prevalence within sexual networks.  
Reliability of participant self-report: An important limitation is the potential for underreporting 
of stigmatized behaviours, such as condomless RAI and substance use. Our experience with 
ACASI in prior studies suggests that this method of data collection may yield more frank 
responses to questions on sensitive topics. 48,91  
Differential retention given the open-label design. At enrolment, we will describe the equipoise 
to evaluate the effectiveness of STI PPT and doxyPEP in the Kenyan setting. After enrolment, we 
will try to address attrition bias by minimizing the burden of study visits and each intervention 
on participants, keeping procedures within a reasonable timeframe and monitoring clinic flow. 
The research team has decades of experience conducting trials with retention averaging ≈85% in 
prior studies (see Preliminary Results), and we will carefully monitor enrolment and visit 
attendance to identify any potential impact on study power. 
Resistance in organisms other than NG. To have ample power for evaluating the effect of our 
two interventions on AMR in NG, we prioritized site support for trial implementation and the 
NAAT and AMR testing required for Aim 1. We recognize that we have not included testing for 
resistance in other organisms such as Staphylococcus aureus or Streptococcus pneumoniae due 
to a ceiling on our allowed budget. If our funding application is successful, we will seek 
additional funding for additional testing of stored swabs and hair samples to explore the 
relationship between STI PPT and doxyPEP and AMR in additional organisms. 
11. Data Management and Analysis 
a. Data Collection 
Data collection procedures and variables to be collected were described in the study procedures, 
detailed above. Data collection procedures that will be used include electronic data capture with 
audio computer-assisted self interviews (ACASI) or computer-assisted personal interviews (CAPI) 
for study participants, case report forms (CRF) for staff to complete documenting study visits, 
recording of interviews with participants and staff, and minuting of staff meetings. Draft study 
tools are included in the appendices; any updates before study launch will be submitted as a 
modification. 

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b. Data Storage 
All study data will be stored securely and password security-protected on a Sharepoint site 
accessible only to the data managers and study PIs. The data collected on desk top computers/ 
laptops/ tablets using ACASI or CAPI programmed in QDS software (Questionnaire Development 
System™, Nova Research Company, Silver Springs, MD, USA) will be encrypted such that only 
password-authorized study staff can access the data. CRF data will be entered after each visit 
using REDCap, a secure web application for building and managing online surveys and databases 
which is freely available through the UW. All participant study files including hard copy CRFs will 
be retained at the study sites for a minimum of 10 years after study completion. Measures taken 
to protect confidentiality will include: 
i. 
De-identified data: The use of participant names to identify study related documents 
will be minimized to the extent possible. All documents bearing participant names will 
be stored apart from documents bearing PTID or Screening ID or barcode numbers. In 
lieu of names, the study ID will be used so that the names will not appear on study 
documents. Data collected from the fingerprint scan will translate into a unique 
identification number that will be accessible only to study staff, at the primary site and 
collaborating sites. No other data than the unique 12-digit number will be stored in the 
shared database. 
ii. Locked Cabinets: All files will be stored in locked cabinets in the MHRC sites, with access 
limited to study staff. 
c. Data analysis 
Data cleaning, recoding and analysis will be conducted using Stata® (StataCorp, College Station, 
Texas) or similar software. Entered data will be checked against the source through line listing and 
all data entry errors corrected. Data will then be checked for logic and consistency using Stata do-
files and all discrepancies reconciled with the source before locking the database.  
Aim 1 data analyses will be intention-to-treat, including participants whether or not they accept 
or continue STI PPT or doxyPEP. Of note, in a small sample (≈80) of MSM attending the Mtwapa 
clinic in 2018-2019, acceptability of STI PPT at quarterly visits in the KWRTP cohort was over 90%; 
COVID-19 led to the discontinuation of this pilot program. Bacterial STI diagnoses (GC, CT, and 
early syphilis) will be reported at baseline and each follow-up visit by arm and by study site. The 
combined STI outcome will be compared between each intervention and the common control arm 
by estimating the relative risks of any STI over follow-up (months 3-18) using a modified Poisson 
model fitted with generalized estimating equations (GEE) methods to account for repeated 
observations for each participant, assuming an independent covariance structure, with site and 
study arm as the only covariates. 47 The test for significance will use a two-sided α=0.05, and 95% 
confidence intervals will be calculated using robust standard errors. The same approach will be 
used for each STI individually. Complete case analysis will be used for the primary efficacy analysis, 
unless substantial imbalance (>8%) in missing primary endpoints by arm occurs. Appropriate 
missing data methods (e.g., imputation) or causal estimation of direct effects will be conducted to 
assess the potential influence of differential missingness by arm. Syndromic infections diagnosed 
and treated at interim visits after 28 days will be defined as infections for the current quarter and 
handled in the analysis as if they were present at the next scheduled visit. Per-protocol analyses 
will also be conducted, as well as analyses controlling for potential confounders such as HIV status 

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if they are unbalanced across arms. Resistance to each antibiotic assessed (i.e., penicillin, 
tetracycline, cefixime, azithromycin, and doxycycline) among NG cases will be tabulated by study 
arm, research site, site of infection, and AMR assessment method. The odds of resistance among 
NG cases with resistance results will be compared between each intervention and the common 
control arm using logistic regression, with repeated measures GEE if repeat infections occur. We 
will also analyse nonparametric trends over time in the proportion of NG isolates demonstrating 
resistance to each antibiotic in the study overall and by study arm. Additional analyses with 
adjustment for baseline STI, sexual risk behavior, and HIV status will also be performed. 
Aim 2 Data Analysis. GEE with appropriate links and robust standard errors will be used to test 
retention across all study arms and to evaluate associations between study arm and the aim 2 
quantitative outcomes collected for both interventions (e.g., AIM, FIM, uptake, AE, symptoms, 
sexual risk behaviour). Factors associated with adherence to doxyPEP will be analysed in the 
population for whom hair samples are tested, based on semiquantitative assessment of high vs. 
low doxycycline concentrations. 30 For all quantitative analyses, patterns of missing data will be 
evaluated, and multiple imputation will be used where appropriate. 
Exit interview notes and transcripts and staff meeting minutes will be translated into English if 
necessary and imported into Dedoose qualitative analysis software. These documents will be 
reviewed separately by two investigators for completeness and initial theme generation. Coding 
and analysis will focusing on participant-level acceptability and satisfaction and on staff-level 
acceptability and feasibility, starting with a deductive approach informed by the theoretical 
framework of acceptability (TFA), a recently-developed approach to acceptability research of 
medical interventions. 73 The components of TFA are affective attitude, burden, ethicality, 
intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy. Additional 
codes emerging from an inductive process will be added as they arise. Codes will be reviewed for 
consistency and inter-coder agreement with consensus code generation by themes. Descriptive 
thematic analyses will be done separately for individuals who refuse participation, trial 
participants (including those who withdraw) and staff. Within these groupings, results will be 
triangulated with relevant quantitative data using joint displays. 
Aim 3 data analysis. Modelling and cost-effectiveness analyses (CEA) overview. After the trial is 
completed, mathematical models will be used to simulate long-term health and cost outcomes 
based on study data and to consider clinical outcomes beyond the scope and time horizon of the 
Aim 1 and Aim 2 work. Using cost and effectiveness outcomes estimated by the model, we will 
calculate the cost-effectiveness of STI PPT and of doxyPEP as interventions. The CEA will follow WHO 
guidelines and Cost of Implementing New Strategies (COINS) recommendations, 74,75 and report 
summary estimates which allow comparison to standard-care syndromic management. In 
addition, a comparison to NAAT-guided treatment (as done in well-resourced settings) will be 
made. CEA results will provide important information to decision makers charged with defining 
priorities and allocating resources.  
Model Design. We will develop a stochastic, network-based model of NG, CT and HIV transmission 
in Kenya. Because syphilis is uncommon among Kenyan MSM and its transmission has not yet 
been extensively modelled, our model will not include syphilis. The general modelling approach 
will follow that developed by Jenness et al for modelling NG, CT, and HIV transmission among 
MSM in the United States. 76 As the model contains more forms of individual heterogeneity and 

28 
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types of transitions than a standard compartmental model, we cannot easily depict it with a 
traditional flow diagram. The model will simulate a population of 100K individuals distinguished 
by the following attributes: age; gender identity; sexual role preference (insertive, receptive, 
versatile); relationship status; NG, CT and HIV status; diagnosis status; time since infection; 
treatment status; and HIV viral load, among possible relevant others revealed by our fieldwork. 
Individuals can undergo any or all of the following transitions: enter the sexually active population; 
age; form or dissolve relationships of different types; become infected with NG, CT, or HIV; 
experience STI and/or HIV symptoms; test; become diagnosed; undergo treatment; discontinue 
ART treatment; re-initiate ART treatment; age out of the population; or die due background age-
specific mortality or HIV-related mortality. Within each partnership, individuals will engage in anal 
intercourse with coital frequency based on a Poisson model fit to study participant data; use 
condoms based on a binomial model also fit to study participant data; choose a sexual role 
(insertive, receptive) for each act of anal intercourse based on individual preferences; and disclose 
STI or HIV status. 
The network dynamics will be modelled using Exponential-family random graph models (ERGMs) 
and their dynamic extension temporal ERGMs (TERGMs) which provide a foundation for 
statistically principled simulation of local and global network structure given a set of target 
statistics from empirical data. The network models will be estimated using the statnet suite of R 
packages that Dr. Goodreau has co-developed; 77 A range of partnership types is common in 
some parts of Eastern Africa, and likely maintains the persistence of transmission at observed 
levels. A unique network model (ERGM or TERGM) will be estimated for each relationship type 
and then used to simultaneously simulate the different types of relationships dynamically on a 
common set of nodes (individuals). The epidemic model will be coded in R and use the EpiModel 
platform for simulating epidemics. 78 We will develop unique modules for vital dynamics, 
transmission, testing, disclosure, treatment, coital acts and condom use based off of code from 
the Jenness model, 76 but highly revised to deal with the specifics of the study population and 
our research data.  
Data Sources, Parameters, and Validation. Population-specific birth and death rates, including 
general mortality and survival trajectories, will be used to parameterize vital dynamics. Data on 
population structure will be drawn from the 2022 Kenya Demographic and Health Survey79 or 
more recent surveys when available. Existing rates of standard care syndromic treatment, NG 
and CT prevalence and morbidity will be estimated from the latest available literature for Kenya 
at the time of model-building. Parameters for sexual network modules will be derived from Aim 
2 sexual network data for MSM and other recent data from Kenya (i.e., the most recent Kenya 
Demographic Survey and Kenya AIDS Indicators Surveys). The efficacy of the WHO-
recommended PPT and doxyPEP interventions and their impact on NG and CT diagnosis and 
treatment for index cases and their partners will be estimated from study data; our model will 
then layer these onto the baseline model to estimate potential population-level impact. 
Sensitivity analyses will be conducted, especially around key parameters of the individual-level 
intervention efficacy. Comparison will also be made to NAAT-guided treatment as done in well-
resourced settings. Model outcomes will include life-years lived with untreated NG or CT, 
incident NG and CT cases averted, and DALYs averted. We will validate the model using available 
Kenyan surveillance data. 80   

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Modeling and CEA Outcomes. The model will be used to project the potential impact of each 
STI control strategy on NG and CT incidence, HIV incidence, and morbidity. Four scenarios will be 
modelled: 
1. Baseline model (current guidelines and practice): standard syndromic treatment for all 
symptomatic individuals 
2. STI PPT intervention: STI PPT delivered in clinic every 3 months to eligible MSM, 
overlaid on standard syndromic treatment  
3. DoxyPEP intervention: self-administration of doxycycline within 24-72 hours after 
condomless anal or vaginal sex, overlaid on standard syndromic treatment and with 
adherence estimates from trial data 
4. NAAT-guided treatment: NAAT screening for eligible MSM every 3 months with 
treatment of laboratory-diagnosed infections, overlaid on standard syndromic 
treatment 
Cost-effectiveness analysis. We will combine effectiveness estimates from the updated 
stochastic model with the cost estimates from each intervention to calculate cost per NG or CT 
case identified and treated, and the incremental cost-effectiveness ratio (ICER) measured as cost 
per incident NG or CT case averted and cost per DALY averted. Disability weights for calculation 
of DALYs will be obtained from the latest global burden of disease study. 81 We will calculate the 
ICER associated with STI PPT and with doxyPEP as the ratio of difference in costs divided by 
difference in DALYs compared to the next most costly strategy over a 10-year horizon. Following 
updated guidelines recommending use of a supply-side threshold to reflect the opportunity cost 
of additional health investment, STI PPT and/or doxyPEP will be considered cost-effective if the 
ICER is ≤USD 500 per DALY averted. 82 We will utilize both the governmental and societal 
perspectives. Univariate and probabilistic sensitivity analyses will be performed to determine 
model robustness and the impact of varying different parameters through their plausible ranges 
on the estimate of cost-effectiveness.  
12. Ethical Considerations 
Ethical approval will be sought from KEMRI Scientific and Ethics Review Unit (SERU). The study 
involves human subjects and the principles below will be observed. 
a. Risks to Human Subjects 
The potential risks of study participation can be divided into risks specifically related to the study 
and, for those participants who are randomized to the STI PPT or doxyPEP arms, the risks 
inherent in taking prophylactic antibiotics.  
Risks and Inconveniences Related to Trial Participation 
• 
There is a small risk of loss of privacy or confidentiality for participants related to study visits, 
in-depth or exit interviews, or contacts by staff, peers, or field workers. This study will 
include questionnaires and counselling on sensitive topics including sexual risk behavior.  
• 
Participants may also experience psychological discomfort during discussion and disclosure 
about stigma, mental health symptoms, and substance use.  
• 
Participants may experience stigma or discrimination if stigmatized sexual risk behavior (e.g., 
male-male sex) is revealed. 

30 
Version 1.1, dated 10 June 2024  
 
• 
Participants may feel some discomfort when blood is drawn or when throat or rectal swabs 
are collected. After a blood draw, participants may have a small bruise or swelling where the 
blood was drawn. 
Potential inconveniences include: 
• 
Intensive monitoring during the 18 months of study follow-up, and 
• 
Collection of hair, urine, throat swabs, rectal swabs, and blood specimens according to the 
study protocol. 
Risks and Inconveniences Inherent to Use of STI PPT or DoxyPEP 
Medical risks associated with STI PPT include those associated with the two medications that will 
be used in the STI PPT regimen, namely cefixime and azithromycin. Medical risks associated with 
doxyPEP include those associated with doxycycline. Potential adverse reactions to each of the 
three medications are summarized below: 
• 
Doxycycline: gastrointestinal symptoms, photosensitivity, yeast infections, increased lactate 
dehydrogenase (LDH), increased serum glucose (1%-10%); esophagitis, rash, headache, skin 
hyperpigmentation (<1%) 
• 
Cefixime: gastrointestinal symptoms (2%->10%); allergic reactions, acute renal failure, 
dizziness, headache, drug fever, hepatitis, hyperbilirubinemia, jaundice, cytopenias, seizures, 
and pseudomembranous colitis (<2%) 
• 
Azithromycin: gastrointestinal symptoms (>10%); pruritus, increased LDH, increased creatine 
phosphokinase (1%-10%); rash, photosensitivity, chest pain, palpitations, angioedema, 
bronchospasm, headache, fatigue, agitation, vertigo, hepatitis, pseudomembranous colitis, 
genital candidiasis (<1%) 
Most medication-related adverse effects should be mild to moderate and resolve within weeks 
at most. Rarely, severe side effects including allergic reactions can occur, and may be life 
threatening. In addition, there is a risk that STI PPT or doxyPEP will increase resistance to 
cefixime, azithromycin, and/or doxycycline. Quantifying this risk is an important focus of the 
proposed work. Of note, medications including injectable ceftriaxone and spectinomycin are 
available for cases of urethritis, pharyngitis, or proctitis that do not respond to first-line 
treatment. Other potential risks and inconveniences related to STI PPT administration or 
doxyPEP use include loss of privacy due to the need for eligibility checking and the 
inconvenience of medication use. Participants who experience persistent or serious adverse 
effects of STI PPT or doxyPEP will be advised to stop this intervention and focus on behavioral 
risk reduction instead.  
b. Adequacy of Protection from Risks 
Every effort will be made to minimize the risks associated with study participation. Experienced 
research staff will counsel participants prior to enrolment, so that they are aware of the risks 
described above. We will have strict guidelines and procedures in order to minimize the potential 
for emotional distress due to questions asked in the ACASI, to physical exams, to in-depth 
interviews for the subset of intervention participants selected, or to exit interviews for individuals 
who withdraw. Participants will be told during the informed consent procedures that some of the 
questions asked may cause discomfort or distress. Participants will be assured of their right to 
refuse to answer any questions they do not wish to answer. Participants will be assured of their 

31 
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right to end an interview prior to completion. To minimize the risk of discomfort, assessments and 
all interviews will be conducted in private areas. If during the course of an ACASI or an in-depth or 
exit interview, the participant demonstrates or articulates signs of distress, the research staff will 
be trained to immediately stop the activity taking place. Referral to mental health and other 
support services will be available onsite or through referrals to local community providers. 
Research staff members will receive initial and ongoing training in ethics and confidentiality, study 
protocols, emergency procedures, mandated reporting procedures, general interviewing skills and 
data management.  
The risk for loss of privacy will be minimized by strict confidentiality procedures. Identifying 
information collected for tracing purposes will be kept in an encrypted contact information file on 
a password-protected laptop computer with an encrypted hard drive. A master electronic file 
including the linkage of names to numbers (used to identify participants who return without a 
numbered study card) will be encrypted and retained on a single computer at each research site 
in a secure location. This master file will be checked each day for duplicates. Consents will be 
stored in a separate area in a locked file cabinet. All personal identifying information will be 
destroyed immediately after the study is completed. In addition, privacy will be protected by 
ensuring that CAPI administration and physical examinations take place in private rooms. 
Recordings from participant interviews will be transcribed and stored on a password-protected 
personal computer. Interviews conducted in Swahili or Dholuo will be simultaneously translated 
into English and transcribed, with back-translation and verification by a different person to ensure 
accuracy.  
Participants will not be identified by name in the interview transcripts, rather by study ID. We will 
also protect privacy by developing individualized procedures for study-related contacts in 
collaboration with each participant. Research staff and peer outreach workers at our three 
research clinics already have 2-10 years of experience maintaining confidentiality and privacy with 
MSM research participants, and are either from the LGBTQ+ community or face social challenges 
due to secondary stigma. Community partners and all newly hired staff and peers will undergo 
rigorous training on the protection of confidentiality and particular need for discretion in working 
with this population, whether in the clinic or community.  
All study procedures will be conducted according to detailed standard operating procedures that 
emphasize participant protections and the voluntary nature of participation. In addition, 
experienced research staff will oversee all ACASI assessments, conduct interviews, and perform 
physical examinations and blood collection. Appropriate clinical monitoring will minimize the risk 
of severe adverse events related to STI PPT or doxyPEP during clinic follow-up. Participants will be 
assured that their non-research care will not be affected by their participation status in this study, 
nor by their responses in questionnaires. Participants will be informed that they have the right to 
withdraw or refuse an examination or sample collection at any point. All study staff involved in 
research procedures will be required to undergo training in Human Subjects protection 
certification and in Good Clinical Practice (GCP), and all laboratory staff will be required to undergo 
periodic training in Good Clinical Laboratory Practice (GCLP).  
Of note, the County Commissioner, Officer Commanding Police Division, the County Health 
Director and the County Medical Officer of Health in each location are aware of our MSM research 
activities, and they support non-discrimination based on sexual orientation. While homosexuality 

32 
Version 1.1, dated 10 June 2024  
 
is illegal in Kenya, there are strong passages in the constitution protecting human rights, and 
judicial, police and health authorities have chosen to emphasize human rights as protecting 
LGBTQ+ individuals. This does not mean, however, that there are no risks to disclosure of same-
sex sexual behaviour, and this study will do everything possible to maintain confidentiality and 
anonymity of study participants. At each site, we have established a community advisory board 
(CAB) to advise us on risks to participants related to study procedures and to assist in monitoring 
social and psychological harm resulting from study participation. These CABs are each currently 
composed of MSM community representatives and local stakeholders at each site, such as lawyers 
with experience in defending LGBTQ+ individuals in the courts, religious leaders, and the local 
County AIDS and STD Control Officer (CASCO) or other Ministry of Health representatives.  
c. Potential Benefits to the Subjects and Others 
All participating individuals will receive risk reduction counselling, condoms and lubricants, and 
screening and treatment for syndromic STI, regardless of their study arm. Standard HIV care or 
prevention will be provided per ongoing procedures at the research clinic, which are updated as 
Kenyan MoH guidelines change. All care provided at the study clinics is free of charge. Of note, 
HIV care and prevention services are available in a non-research (program) context in these clinics 
and at several sites in Nairobi, Kisumu and Mombasa, should individuals not want to participate 
in this research study. 
In summary, potential benefits to the subjects include: 
1. All trial participants may benefit in terms of access to risk reduction counselling and 
screening for syndromic STI, with syndromic management and partner notification services 
available onsite. 
2. For intervention arm participants who receive STI PPT or doxyPEP during follow-up, there is 
the potential to reduce STI acquisition. 
3. All participants will contribute to a study that will evaluate ways of improving STI control 
among Kenyan MSM. 
Potential benefits to others include: 
1. From the perspective of the population from which participants be recruited, this study 
offers the potential for MSM to benefit from the testing and evaluation of two STI control 
interventions which have the potential to improve STI control over the standard of care, 
syndromic treatment.  
2. This study has the potential to reduce STI transmission in the study population and their 
sexual networks, which could in turn reduce HIV transmission in a key population that is 
estimated to account for 15% of new HIV infections in Kenya. 
Given the low likelihood of significant risks to participants, the risks seem reasonable in relation 
to anticipated benefits. 
d. Informed consent  
Written informed consent will be obtained by trained study staff fluent in Dholuo, English and 
Kiswahili in a private counselling room at a participating research clinic. Staff will provide 
information on the study, screen individuals for eligibility after asking oral permission, and offer 
participation to individuals who are eligible. The informed consent document will describe the 
purpose of the study, the procedures to be followed, and the risks and benefits of participation. 

33 
Version 1.1, dated 10 June 2024  
 
During the consent process, staff will explain the study procedures, with an emphasis on 
features that differ from routine programmatic services, highlighting the risks and benefits of 
study participation.  
Participants will be able to discuss their research participation with study staff at any time, and 
to ask any questions they may have. If participants change their minds about continuing and 
wish to withdraw, they may do so at any time. Our informed consent documents stress that all 
participation is voluntary, and they provide contacts should participants have any questions 
about the study or their rights. 
Consent documents will be available in Dholuo, English and Kiswahili. Written informed consent 
will be obtained from all participants; persons incapable of consenting are excluded. Potential 
participants who would like to take additional time to consider their enrolment will be 
encouraged to do so. Staff will emphasize that participation is voluntary, and that participants 
can refuse to answer any question or undergo any procedure or can discontinue participation at 
any time without penalty.  
If an individual is illiterate, all procedures, risks and benefits will be explained and the individual 
will be given the option of having a friend or family member or a trained consultant who is not a 
member of the research staff to be present to further explain the study. In these cases, the 
friend, family member, or trained consultant will be asked to sign the informed consent 
document as a witness. 
Research staff will be trained in assessing subjects’ understanding of the information presented, 
by asking the participant to describe the purpose of the research and his understanding of 
procedures, and by using additional probes if needed to ensure adequate comprehension. If it is 
determined that a participant is unable to understand and therefore not able to provide 
informed consent, that individual will be excluded from the research. 
Participants will be informed of the procedures for ensuring confidentiality, including use of 
unique non-personally identifying ID numbers instead of names on research materials, and the 
maintenance of data in encrypted computer databases and locked filing cabinets in locked 
rooms. Enrolled participants will be provided with a signed and dated copy of the informed 
consent document before they leave the study site. 
Withdrawal of participants. Participants will be assured that their non-research care will not be 
affected by their participation status in this study, nor by their responses in questionnaires. 
Participants will be informed that they have the right to withdraw or refuse an examination or 
sample collection at any point. At the time of withdrawal for any reason (e.g., a move from the 
study area), a semi-structured exit interview will be conducted regarding experiences, including 
any social harms of study participation. Consent will be obtained for these interviews, and 
permission will be asked for digital recording. The only other circumstances in which we would 
withdraw a participant from the study without their consent would be due to demonstrated 
inability or unwillingness to participate in study visits; this decision will be made by the entire 
team after documentation of multiple events of failure to participate. 
e. Confidentiality of information obtained 
Study team members will have access to participant names and contact information, which is 
needed for scheduling and sending reminders about clinic visits and exit interviews and for 

34 
Version 1.1, dated 10 June 2024  
 
contacting patients in the event of a test result needing action. These participant identifiers will 
not be recorded in the study database but will be included in a link log at each site. The link log 
will be used to record participant names, contact information, and study ID numbers, and will be 
maintained until participant enrolment and follow-up are complete, for the purposes of avoiding 
duplicate enrolments and assisting with retention. During the trial, contact information will be 
retained in order to reach out to any participants who have abnormal laboratory results or miss 
study visits. We may also use this information to follow up with any participant who experiences 
an adverse event or social harm, in order to provide support and ascertain the status of the event 
or harm after interventions by the study team or outside providers. This link log will be accessed 
for visit tracking, scheduling, and tracking purposes, and will be destroyed after participant 
enrolment and follow-up are completed. If participants consent to this, we may also use this 
information to contact participants about future studies that build on this work. 
Fingerprint scanning technology, which we have used successfully in the past, will also be used to 
avoid duplicate enrolment if resources permit. This technology would link the participant’s unique 
fingerprint pattern to the participant’s study ID number; no participant name or contact 
information would be recorded in the fingerprint scanning database. In accordance with the Kenya 
Data Protection Act, all fingerprint scanning data will be stored locally in Kenya only. Fingerprint 
scanning data will be destroyed after the study is completed, along with other personal identifying 
data. 
Data will be obtained directly from the subjects (ACASI, intervention feedback, exit interview) or 
subjects’ specimens (blood, urine, swabs, hair), from clinic records (attendance, services 
rendered, intervention delivery), and from observations made for cost analysis (clinic flow, staff 
time spent on various activities, costs of equipment and supplies). All participant data, including 
exit interview transcripts, will be stored for future use in de-identified form. Participant ID 
numbers will be used, and no direct identifiers will be stored in relation to these data. Biologic 
specimens will be stored for testing for the purposes detailed above in the procedures section. All 
de-identified data produced in the course of the project will be preserved. The final 
dataset will include self-reported demographic and behavioral data from ACASI surveys, 
clinical data from participant symptoms and focused physical exams, and laboratory data 
from blood and genitourinary specimens provided.  
To summarize our procedures related to confidentiality: 
• 
De-identified data: All documents bearing participant names (e.g., consent documents) will 
be stored apart from documents bearing screening or participant ID numbers. In lieu of 
names, the study ID will be used on the screening questionnaires and interview transcripts.  
• 
Locked Cabinets: All files will be stored in locked cabinets in the research data office at each 
clinical site, with access limited to study staff. These office are accessible only to the site PI 
and data management staff, who have keys for access. Non staff members who may need to 
perform tasks in the data office, such as carpentry or repairs, are allowed into the room only 
when the site PI or Data Manager is present, and care will be taken to ensure that 
participant records are not in view.  
• 
Access to the Link Log file, which will contain names, contact information, and participant 
IDs, will be limited to authorized study staff members through the use of password 
protections.  

35 
Version 1.1, dated 10 June 2024  
 
No participant identifiers other than the participant ID will be recorded on any data collection 
form or interview transcript. 
f. Data sharing 
We will share de-identified individual-participant level data, in accordance with an open data 
approach, taking appropriate measures such as expert determination to identify for removal any 
specific variables that could potentially lead to identification of individuals. Plans for data de-
identification and sharing are reflected in the informed consent forms. To facilitate interpretation 
of the data, a data dictionary describing all variables in the dataset, the study protocol, and all 
data collection instruments will be created, shared, and associated with the relevant datasets. 
Documentation and support materials will be compatible with the clinicaltrials.gov Protocol 
Registration Data Elements. 
De-identified datasets will be made available at the trial's completion, and datasets used for 
statistical analysis will be made available in the UW Research Works Archive as manuscripts are 
published. Dr. Graham, as the principal investigator, will oversee and manage data sharing, 
assisted by the lead investigator at each site (Dr. Otieno in Kisumu, Dr. Kimani in Nairobi, and Dr. 
Sanders in Mombasa).  
We will ask permission in our consent for possible future use of the data in related studies. 
Possible future uses of study data will be related to secondary analyses to investigate factors 
influencing the physical, mental, and sexual health of gay, bisexual and other men who have sex 
with men in Kenya. 
g. Data safety and monitoring plan 
Overall framework for safety monitoring and what will be monitored: The MPIs will take overall 
responsibility for making sure that the trial is conducted according to the approved protocol.  
Specifically, Dr. Sanders will be responsible for all elements of the field work conducted in Kenya, 
and Dr. Graham will be responsible for all elements of the work conducted in Seattle. Both MPIs 
will be supported by the two site PIs, Dr. Otieno and Dr. Kimani. Adverse events (AEs), including 
severe adverse events (SAEs), will be reported to SERU, the UW Human Subjects Division (HSD), 
and a Data Safety and Monitoring Board (DSMB; see below for details). Specific parameters that 
will be monitored will include: 
• 
Signs and symptoms of systemic effects that could be related to exposure to the sexually 
transmitted infection (STI) periodic presumptive treatment (PPT) regimen (i.e., oral cefixime 
and azithromycin) or to doxycycline post-exposure prophylaxis (doxyPEP) 
• 
Adverse events related to study procedures, including social harms 
Because cefixime, azithromycin, and doxycycline are already approved treatments for gonorrhea 
and chlamydia, and STI prophylaxis is currently recommended by the WHO for MSM, we believe 
that an investigational new drug (IND) application is not needed for this study. Nonetheless, if 
funded, we will bring this question to NIAID program staff and the Kenya Poisons Board, and would 
prepare an investigator-initiated IND application if needed. Of note, there is an ongoing trial of 
doxyPEP for adolescent girls and young women in Kenya (NCT04050540) led by a UW-affiliated 
MPI (Dr. Jared Baeten); Dr. Celum is a collaborator on this trial and is available to help guide 
regulatory applications as needed. 

36 
Version 1.1, dated 10 June 2024  
 
Frequency of monitoring: Interim analyses will be presented to a DSMB when enrolment reaches 
50%, and quarterly thereafter until follow-up is completed. The purpose of these reviews will be 
to assess recruitment, retention, and safety. Laboratory testing for study endpoints will not be 
completed until after participant follow-up has ended. 
Process for reporting adverse events:  Adverse events will be reported on a case report form (CRF) 
developed for this purpose.  This will include an assessment of the severity of the event (which 
influences the timeline for reporting).  The following guidelines will be used to quantify severity: 
• 
Mild: events require minimal or no treatment and do not interfere with the patient’s daily 
activities. 
• 
Moderate: events result in a low level of inconvenience or concern with the therapeutic 
measures.  Moderate events may cause some interference with functioning. 
• 
Severe: events interrupt a patient’s usual daily activity and may require systemic drug 
therapy or other treatment.  Severe events are usually incapacitating. 
• 
Life threatening:  any adverse drug experience that places the patient or subject, in the view 
of the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does 
not include a reaction that had it occurred in a more severe form, might have caused death. 
We will also document changes in the severity of adverse events, to allow assessment of the 
duration of the event at each level of intensity.  Adverse events characterized as intermittent will 
require documentation of onset and duration of each episode. 
Serious Adverse Events will be defined as AEs that meet one or more of the following conditions: 
• 
Death during the period of protocol-defined surveillance 
• 
Life-threatening event (defined as a subject at immediate risk of death at the time of the 
event) 
• 
An event requiring inpatient hospitalization or prolongation of existing hospitalization during 
the period of protocol-defined surveillance  
• 
Results in a persistent or significant disability/incapacity 
• 
Any other important medical event that may not result in death, be life threatening, or 
require hospitalization, may be considered a serious adverse experience when, based upon 
appropriate medical judgment, the event may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed above.  Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
All SAEs will be recorded on the appropriate AE CRF, followed through resolution by a study 
clinician, and reviewed and evaluated by the MPI team and the Site PI responsible for the 
participant. The specific procedures for reporting of AEs depend on their severity, as detailed 
above.  The MPI team will be responsible for reporting all AEs that are observed or reported during 
the study. Information to be collected includes event description, time of onset, investigator 
assessment of severity, relationship to study product, and time of resolution/stabilization of the 
event.  All adverse events occurring while in study will be documented appropriately regardless 
of relationship.   
Any medical condition that is present at the time that the subject is screened will be considered 
as baseline and not reported as an AE.  However, if the condition deteriorates at any time during 

37 
Version 1.1, dated 10 June 2024  
 
the study, it will be recorded as an AE.  Study staff will document AEs and SAEs from the Enrollment 
Visit through the End of Study Evaluation at month 18. We will follow NIAID guidelines for 
reporting of adverse events; SAEs will be reported to the SERU and the UW HSD within 72 hours.  
Non-severe AEs will be reported in regular scheduled reports to SERU and the UW HSD.  In 
addition, the summary of all AEs (including SAEs) will be presented to the DSMB in an interim 
report.   
h. Data safety and monitoring board 
Safety oversight will be under the direction of a DSMB composed of several independent experts 
in infectious diseases and STI control.  This will include at least one Kenyan medical professional 
and at least one independent statistician from the UW. The DSMB will review the protocol and a 
detailed monitoring plan including dummy tables for enrolment and retention data and adverse 
events prior to study initiation.  Interim analyses will be presented to the DSMB at the frequency 
described above to assess recruitment, retention, and safety.  In addition, the MPI team will 
request a safety review by the DSMB if there is more than one unexpected SAE that is attributable 
to the study product or procedures.  No interim analysis of outcomes is planned, as lab testing for 
the primary and exploratory endpoints will be completed after participant involvement has been 
completed. Dr. Graham is currently serving on a DSMB for an NIH-funded trial of an HIV treatment 
support intervention (NCT05046392, PI Ramsey) and therefore has experience with trial 
monitoring by a DSMB. 
i. 
Handling adverse events 
Each research site has clinical staff on hand to assist in the event of bruising or bleeding after 
phlebotomy and counselling staff available to support participants with addressing social harms 
or discomfort with questions. Most mild or moderate adverse events, such as rash or nausea, can 
be managed by the clinical officers at each site, with oversight by licensed physicians as needed. 
Participants with severe or life-threatening adverse events such as anaphylaxis will be stabilized 
at the study site and emergently transferred to a local medical facility for treatment. Of note, we 
expect severe or life-threatening reactions to the commonly used antibiotics that will be provided 
in our two interventions to be very rare. Each participating clinic also has counselling staff and 
support for persons with depressive symptoms, stigma, or substance abuse problems. We will 
conduct no medical diagnostic or genetic testing in this study other than the STI testing described 
in the protocol. 
Adverse Events Facilities:  Our research clinics will have all the facilities and equipment necessary 
to handle mild or moderate adverse events. Participants with severe or life-threatening adverse 
events such as anaphylaxis will be stabilized at the study site and emergently transferred to a local 
medical facility for treatment. While exclusion of patients with prior allergic reactions will help 
safeguard against such events, we will ensure that each clinic team has up-to-date first aid training 
and supplies in the event of such an emergency. 
Financial Responsibilities:  The study team will provide treatment for physical injuries that are 
mild or moderate on site, free of charge. We are obtaining quotes for trial insurance and will have 
this in place prior to enrolment. The NRHS team has had a good experience working with Takaful 
Insurance Company, and we are comparing a quote from Takaful with quotes from other similar 
companies. 

38 
Version 1.1, dated 10 June 2024  
 
13. Expected application of the results 
The findings of this study will be relevant to participants, community organizations serving 
cisgender MSM, policy makers, and agencies considering at-risk populations for efficacy trial 
evaluation of new products. The findings will be published in relevant peer reviewed journals and 
presented at national and international conferences, such as the STI/HIV collaborative meeting in 
Nairobi, and the biannual International Society for Sexually Transmitted Diseases Conference. 
 
 
14. Time Frame/Duration of the Project 
 
2024 
2025 
2026 
2027 
2028 
ACTIVITY 
Q 
1-2 
Q 
3-4 
Q 
1-2 
Q 
3-4 
Q 
1-2 
Q 
3-4 
Q 
1-2 
Q 
3-4 
Q 
1-2 
Q 
3-4 
1) Protocol development, 
review and approval 
x 
 
 
 
 
 
 
 
 
 
2) Training of study staff  
 
x 
 
 
 
 
 
 
 
 
3) Engagement of 
stakeholders 
 
x 
 
 
 
 
 
 
 
 
4) Enrolment and 
quarterly visits 
 
x 
x 
x 
x 
x 
x 
 
 
 
5) NAAT CT/NG analysis 
 
 
 
 
 
x 
x 
 
 
 
6) Data analysis (interim 
report) 
 
 
 
 
 
x 
x 
 
 
 
7) Modelling and cost-
effectiveness analysis 
 
 
 
 
 
x 
x 
x 
 
 
8) Results write up and 
dissemination  
 
 
 
 
 
 
 
 
x 
x 
15. Budget 
Budget (Year 1) 
US$ 
Ksh 
Personnel 
779,007 124,641,120 
Ethical/scientific review and translations 
8,000 
1,280,000 
Office supplies 
21,600 
3,456,000 
Clinical supplies 
12,711 
2,033,760 
Medications for interventions 
56,948 
9,111,680 
Laboratory supplies 
19,148 
3,063,680 
Participant reimbursement 
25,000 
4,000,000 
Shipping within Kenya 
4,000 
640,000 
Overhead 8% 
74,113 
11,858,080 
Total Year 1 
1,000,527 160,084,320 
Total Over 5 Years 
5,000,000 800,000,000 

39 
Version 1.1, dated 10 June 2024  
 
Exchange rate: $1.00 = 160 KSh 
 
 
16. Budget Justification 
Cost categories are provided for Year 1 (total US$ 1,000,527), which is currently awarded.  The total 
budget for the 5 study years is US$ 5 million, with funding for years after Year 1 to be awarded 
contingent upon study progress. 
Personnel. This line item includes salaries and fringe benefits for the site PIs and staff at the 3 study 
sites (Kisumu, Nairobi, and Mombasa), for Dr. Sanders at the Aurum Institute, and for Dr. Graham and 
co-investigators, consultants and grant administrators at the University of Washington. 
Ethical/scientific review and translations. This line item includes payment of KEMRI ERC fees for non-
KEMRI investigators, payment of NACOSTI registration, and payment for review by the Kenya 
Pharmacy and Poisons Board. Translation will be done for informed consent documents (submitted in 
English, Kiswahili, and Dholuo) and for case report forms after approval. 
Office supplies. This line item covers the cost of office supplies at the 3 sites, including stationary, 
telephone and internet support, printing and photocopying. 
Clinical supplies. This line item includes medical supplies such as exam gloves and lights, sterile urine 
collection cups, alcohol swabs, vacutainers, needles, and biohazard bags. 
Medication for interventions. This line item includes purchase and storage costs for the three study 
drugs: doxycycline, cefixime, azithromycin. 
Laboratory supplies. This line item includes supplies for syphilis testing, collection kits for CT and NG 
testing, and supplies for Gram stain, culture, and sensitivity of urethral discharge. CT/NG NAAT testing 
will be done from year 4 onward in bulk in Mombasa. 
Participant reimbursements. Enrolment of the 2900 participants will start in second half of year 1, and 
will continue through year 3. Participants will make 7 visits in total and be reimbursed at 1000 KSh per 
visit.  
Shipping within Kenya. Medications and laboratory supplies will be shipped to all three sites after 
purchase centrally. Samples will be shipped from Kisumu and Nairobi to the University of 
Washington/University of Nairobi laboratory in Mombasa in batches. 
Overhead on grants from the United States NIH is allowed at 8% of direct costs. 
17. Role of Investigators 
Name 
Roles  
Responsibilities 
Susan M. 
Graham 
PI 
Protocol development, questionnaire design, data analysis, study 
oversight 
Eduard J. 
Sanders 
Co-PI 
Protocol development, questionnaire design, data analysis, study 
oversight 
Joshua Kimani 
Site PI 
Protocol development, questionnaire design, study oversight 
Fred Otieno 
Site PI 
Protocol development, questionnaire design, study oversight 
Deven Hamilton 
Co-I 
Modelling the impact of intervention scale up (Aim 3) 
R. Scott 
McClelland  
Co-I 
Study oversight Ganjoni, implementation science expertise 
Monisha Sharma  Co-I 
Cost effectiveness analysis 

40 
Version 1.1, dated 10 June 2024  
 
Olusegun O Soge  Co-I 
Testing of gonorrhoea samples for resistance mutations of 
clinical importance 
Robert C. Bailey 
Consultant Technical assistance and administrative support at the Kisumu 
site as needed 
Connie Celum 
Consultant Expertise in doxyPEP and clinical trials, support to the Leadership 
team as needed 
Steven 
Goodreau 
Consultant Support to Dr. Hamilton and the leadership team on modelling as 
needed 
 
 
18. References 
1. 
De Baetselier I, Vuylsteke B, Yaya I, et al. To Pool or Not to Pool Samples for Sexually Transmitted Infections 
Detection in Men Who Have Sex With Men? An Evaluation of a New Pooling Method Using the GeneXpert 
Instrument in West Africa. Sex Transm Dis 2020; 47(8): 556-61. 
2. 
Jones J, Sanchez TH, Dominguez K, et al. Sexually transmitted infection screening, prevalence and incidence 
among South African men and transgender women who have sex with men enrolled in a combination HIV 
prevention cohort study: the Sibanye Methods for Prevention Packages Programme (MP3) project. J Int AIDS Soc 
2020; 23 Suppl 6: e25594. 
3. 
Otieno F, Ng'ety G, Okall D, et al. Incident gonorrhoea and chlamydia among a prospective cohort of men who 
have sex with men in Kisumu, Kenya. Sex Transm Infect 2020. 
4. 
Sanders EJ, Thiong'o AN, Okuku HS, et al. High prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae 
infections among HIV-1 negative men who have sex with men in coastal Kenya. Sex Transm Infect 2010; 86(6): 
440-1. 
5. 
Grijsen ML, Graham SM, Mwangome M, et al. Screening for genital and anorectal sexually transmitted infections 
in HIV prevention trials in Africa. Sex Transm Infect 2008; 84(5): 364-70. 
6. 
Ouedraogo HG, Zida S, Compaore TR, et al. Seroepidemiology of syphilis among men who have sex with men in 
Burkina Faso, West Africa. Eur J Clin Microbiol Infect Dis 2019; 38(10): 1803-9. 
7. 
Twahirwa Rwema JO, Herbst S, Hamill MM, et al. Cross-sectional assessment of determinants of STIs among men 
who have sex with men and transgender women in Kigali, Rwanda. Sex Transm Infect 2022; 98(3): 178-87. 
8. 
Leu RH. Complications of coexisting chlamydial and gonococcal infections. Postgrad Med 1991; 89(7): 56-60. 
9. 
Jones J, Weiss K, Mermin J, et al. Proportion of Incident Human Immunodeficiency Virus Cases Among Men Who 
Have Sex With Men Attributable to Gonorrhea and Chlamydia: A Modeling Analysis. Sex Transm Dis 2019; 46(6): 
357-63. 
10. 
Agutu CA, Ngetsa CJ, Price MA, et al. Systematic review of the performance and clinical utility of point of care 
HIV-1 RNA testing for diagnosis and care. PLoS One 2019; 14(6): e0218369. 
11. 
Voirin N, Allam C, Charre C, et al. Optimizing strategies for Chlamydia trachomatis and Neisseria gonorrhoeae 
screening in men who have sex with men: a modelling study. Clin Infect Dis 2019. 
12. 
Prevention and control of sexually transmitted infections (STIs) in the era of oral pre-exposure prophylaxis (PrEP) 
for HIV. Geneva: World Health Organization; 2019. 
13. 
World Health Organization. Guidelines: Prevention and treatment of HIV and other sexually transmitted 
infections among men who have sex with men and transgender people: Recommendations for a public health 
approach. Geneva, Switzerland: WHO Press; 2011. 
14. 
Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually 
transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY 
trial. Lancet Infect Dis 2018; 18(3): 308-17. 
15. 
Luetkemeyer A, Dombrowski J, Cohen S, et al. Doxycycline post-exposure prophylaxis for STI prevention among 
MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI's in a 
randomized trial.  AIDS 2022. Montreal, Quebec; 2022. 
16. 
Room IP. Efficacy of a Meningococcal B Vaccine and a Preventive Antibiotic in Reducing the Risk of Sexually 
Transmitted Infections. Available at https://presse.inserm.fr/en/efficacy-of-a-meningococcal-b-vaccine-and-a-
preventive-antibiotic-in-reducing-the-risk-of-sexually-transmitted-infections/65739/ 
17. 
St Cyr S, Barbee L, Workowski KA, et al. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020. 
MMWR Morb Mortal Wkly Rep 2020; 69(50): 1911-6. 
18. 
Evers YJ, van Liere GAFS, Dukers-Muijrers NHTM, Hoebe CJPA. Use of doxycycline and other antibiotics to 
prevent STIs among men who have sex with men visiting sexual health clinics in the Netherlands. Sex Transm 
Infect 2020; 96(7): 550-1. 
19. 
Fusca L, Hull M, Ross P, et al. High Interest in Syphilis Pre-exposure and Post-exposure Prophylaxis Among Gay, 
Bisexual and Other Men Who Have Sex With Men in Vancouver and Toronto. Sex Transm Dis 2020; 47(4): 224-
31. 

41 
Version 1.1, dated 10 June 2024  
 
20. 
Grant JS, Stafylis C, Celum C, et al. Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections. Clin 
Infect Dis 2020; 70(6): 1247-53. 
21. 
Proctor E, Silmere H, Raghavan R, et al. Outcomes for implementation research: conceptual distinctions, 
measurement challenges, and research agenda. Adm Policy Ment Health 2011; 38(2): 65-76. 
22. 
Proctor EK, Landsverk J, Aarons G, Chambers D, Glisson C, Mittman B. Implementation research in mental health 
services: an emerging science with conceptual, methodological, and training challenges. Adm Policy Ment Health 
2009; 36(1): 24-34. 
23. 
Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually 
transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY 
trial. Lancet Infect Dis 2018; 18(3): 308-17. 
24. 
Quilter LAS, Obondi E, Kunzweiler C, et al. Prevalence and correlates of and a risk score to identify asymptomatic 
anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya. Sex Transm 
Infect 2019; 95(3): 201-11. 
25. 
World Health Organization. WHO guidelines for the treatment of Neisseria gonorrhoeae. Geneva, Switzerland: 
WHO Press; 2016. 
26. 
Ministry of Health. Kenya National Guidelines for Prevention, Management, and Control of Sexually Transmitted 
Infections. Nairobi, Kenya; 2018. 
27. 
Unemo M, Golparian D, Sánchez-Busó L, et al. The novel 2016 WHO Neisseria gonorrhoeae reference strains for 
global quality assurance of laboratory investigations: phenotypic, genetic and reference genome 
characterization. J Antimicrob Chemother 2016; 71(11): 3096-108. 
28. 
Durukan D, Read TRH, Bradshaw CS, et al. Pooling Pharyngeal, Anorectal, and Urogenital Samples for Screening 
Asymptomatic Men Who Have Sex with Men for Chlamydia trachomatis and Neisseria gonorrhoeae. J Clin 
Microbiol 2020; 58(5). 
29. 
Wilson JD, Wallace HE, Loftus-Keeling M, et al. Swab-Yourself Trial With Economic Monitoring and Testing for 
Infections Collectively (SYSTEMATIC): Part 2. A Diagnostic Accuracy and Cost-effectiveness Study Comparing 
Rectal, Pharyngeal, and Urogenital Samples Analyzed Individually, Versus as a Pooled Specimen, for the 
Diagnosis of Gonorrhea and Chlamydia. Clin Infect Dis 2021; 73(9): e3183-e93. 
30. 
Angelakis E, Armstrong N, Nappez C, Richez M, Chabriere E, Raoult D. Doxycycline assay hair samples for testing 
long-term compliance treatment. J Infect 2015; 71(5): 511-7. 
31. 
Cehovin A, Harrison OB, Lewis SB, et al. Identification of Novel Neisseria gonorrhoeae Lineages Harboring 
Resistance Plasmids in Coastal Kenya. J Infect Dis 2018; 218(5): 801-8. 
32. 
Kivata MW, Mbuchi M, Eyase F, et al. Plasmid mediated penicillin and tetracycline resistance among Neisseria 
gonorrhoeae isolates from Kenya. BMC Infect Dis 2020; 20(1): 703. 
33. 
Soge OO, Issema R, Bukusi E, et al. Predominance of high-level tetracycline-resistant Neisseria gonorrhoeae in 
Kenya: Implications for global implementation of doxycycline post-exposure prophylaxis for prevention of 
sexually transmitted infections. Sex Transm Dis 2023; 50(5):317-319. 
34. 
Bignell C, Ison CA, Jungmann E. Gonorrhoea. Sex Transm Infect 2006; 82 Suppl 4(Suppl 4): iv6-9. 
35. 
Pabbaraju K, Wong S, Song JJ, Singh AE, Read R, Drews SJ. Utility of specimens positive for Neisseria gonorrhoeae 
by the Aptima Combo 2 assay for assessment of strain diversity and antibiotic resistance. J Clin Microbiol 2013; 
51(12): 4156-60. 
36. 
Pond MJ, Hall CL, Miari VF, et al. Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly 
from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy. J Antimicrob 
Chemother 2016; 71(4): 897-902. 
37. 
Soge O, Wakatake E, Thibault C, et al. Performance of ResistancePlus (R) GC Assay for Reflex Culture-
Independent Detection of Ciprofloxacin Resistance in   Neisseria gonorrhoeae. Sex Transm Dis 2022; 49: S4-S5. 
38. 
Martin IM, Ison CA, Aanensen DM, Fenton KA, Spratt BG. Rapid sequence-based identification of gonococcal 
transmission clusters in a large metropolitan area. J Infect Dis 2004; 189(8): 1497-505. 
39. 
Mortimer TD, Zhang JJ, Ma KC, Grad YH. Loci for prediction of penicillin and tetracycline susceptibility in Neisseria 
gonorrhoeae: a genome-wide association study. Lancet Microbe 2022; 3(5): e376-e81. 
40. 
Mortimer TD, Grad YH. Applications of genomics to slow the spread of multidrug-resistant Neisseria 
gonorrhoeae. Ann N Y Acad Sci 2019; 1435(1): 93-109. 
41. 
Peterson SW, Martin I, Demczuk W, et al. Multiplex real-time PCR assays for the prediction of cephalosporin, 
ciprofloxacin and azithromycin antimicrobial susceptibility of positive Neisseria gonorrhoeae nucleic acid 
amplification test samples. J Antimicrob Chemother 2020; 75(12): 3485-90. 
42. 
Peterson SW, Martin I, Demczuk W, et al. Molecular Assay for Detection of Genetic Markers Associated with 
Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae. J Clin Microbiol 2015; 53(7): 2042-8. 
43. 
Wong LK, Hemarajata P, Soge OO, Humphries RM, Klausner JD. Real-Time PCR Targeting the. Antimicrob Agents 
Chemother 2017; 61(11). 
44. 
Trembizki E, Buckley C, Donovan B, et al. Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S 
rRNA mutations associated with azithromycin resistance. J Antimicrob Chemother 2015; 70(12): 3244-9. 
45. 
Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology 
of bacterial resistance. Microbiol Mol Biol Rev 2001; 65(2): 232-60 ; second page, table of contents. 

42 
Version 1.1, dated 10 June 2024  
 
46. 
Teker B, de Vries H, Heijman T, van Dam A, Schim van der Loeff M, Jongen VW. Spontaneous clearance of 
asymptomatic anogenital and pharyngeal. Sex Transm Infect 2022. 
47. 
Yelland LN, Salter AB, Ryan P. Performance of the modified Poisson regression approach for estimating relative 
risks from clustered prospective data. Am J Epidemiol 2011; 174(8): 984-92. 
48. 
van der Elst EM, Okuku HS, Nakamya P, et al. Is audio computer-assisted self-interview (ACASI) useful in risk 
behaviour assessment of female and male sex workers, Mombasa, Kenya? PLoS One 2009; 4(5): e5340. 
49. 
Wahome E, Thiong'o AN, Chirro O, et al. An empiric risk score to guide PrEP uptake in MSM in coastal Kenya.  
Conference on Retroviruses and Opportunistic Infection. Seattle, WA, USA; 2017. 
50. 
Sanders EJ, Okuku HS, Smith AD, et al. High HIV-1 incidence, correlates of HIV-1 acquisition, and high viral loads 
following seroconversion among MSM. AIDS 2013; 27(3): 437-46. 
51. 
Kunzweiler CP, Bailey RC, Okall DO, Graham SM, Mehta SD, Otieno FO. Factors Associated With Prevalent HIV 
Infection Among Kenyan MSM: The Anza Mapema Study. J Acquir Immune Defic Syndr 2017; 76(3): 241-9. 
52. 
Mehta SD, Okall D, Graham SM, N'gety G, Bailey RC, Otieno F. Behavior Change and Sexually Transmitted 
Incidence in Relation to PREP Use Among Men Who Have Sex with Men in Kenya. AIDS Behav 2021; 25(7): 2219-
29. 
53. 
Weiner BJ, Lewis CC, Stanick C, et al. Psychometric assessment of three newly developed implementation 
outcome measures. Implement Sci 2017; 12(1): 108. 
54. 
Rabkin JG, Markowitz JS, Ocepek-Welikson K, Wager SS. General versus systematic inquiry about emergent 
clinical events with SAFTEE: implications for clinical research. Journal of clinical psychopharmacology 1992; 
12(1): 3-10. 
55. 
Walsh JC, Mandalia S, Gazzard BG. Responses to a 1 month self-report on adherence to antiretroviral therapy 
are consistent with electronic data and virological treatment outcome. Aids 2002; 16(2): 269-77. 
56. 
Oyugi JH, Byakika-Tusiime J, Charlebois ED, et al. Multiple validated measures of adherence indicate high levels 
of adherence to generic HIV antiretroviral therapy in a resource-limited setting. JAIDS 2004; 36(5): 1100-2. 
57. 
Lu M, Safren SA, Skolnik PR, et al. Optimal recall period and response task for self-reported HIV medication 
adherence. AIDS Behav 2008; 12(1): 86-94. 
58. 
Graham SM, Masese L, Gitau R, et al. Antiretroviral adherence and development of drug resistance are the 
strongest predictors of genital HIV-1 shedding among women initiating treatment. J Infect Dis 2010; 202(10): 
1538-42. 
59. 
Ndubuka NO, Ehlers VJ. Adult patients' adherence to anti-retroviral treatment: a survey correlating pharmacy 
refill records and pill counts with immunological and virological indices. International journal of nursing studies 
2011; 48(11): 1323-9. 
60. 
Institute of Medicine (US) Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research 
Gaps and Opportunities. The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation 
for Better Understanding: The National Academies Press; 2011. 
61. 
Fay H, Baral SD, Trapence G, et al. Stigma, Health Care Access, and HIV Knowledge Among Men Who Have Sex 
With Men in Malawi, Namibia, and Botswana. AIDS Behav. 
62. 
Balkus JE, Brown E, Palanee T, et al. An Empiric HIV Risk Scoring Tool to Predict HIV-1 Acquisition in African 
Women. J Acquir Immune Defic Syndr 2016; 72(3): 333-43. 
63. 
Carroll JJ, Heffron R, Mugo N, et al. Perceived Risk Among Human Immunodeficiency Virus Serodiscordant 
Couples in East Africa Taking Oral Pre-Exposure Prophylaxis. Sex Transm Dis 2016; 43(8): 471-5. 
64. 
National AIDS and STI Control Program. Guidelines for HIV Testing Services in Kenya. In: Health Mo, editor. 
Nairobi, Kenya: NASCOP; 2015. 
65. 
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders 
Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol 
Consumption--II. Addiction (Abingdon, England) 1993; 88(6): 791-804. 
66. 
Peltzer K, Davids A, Njuho P. Alcohol use and problem drinking in South Africa: findings from a national 
population-based survey. African journal of psychiatry; 14(1): 30-7. 
67. 
Jordan HT, Farley MM, Craig A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B 
streptococcal disease: a multistate, population-based analysis. The Pediatric infectious disease journal 2008; 
27(12): 1057-64. 
68. 
Skinner HA. The drug abuse screening test. Addictive behaviors 1982; 7(4): 363-71. 
69. 
Secor AM, Wahome E, Micheni M, et al. Depression, substance abuse and stigma among men who have sex with 
men in coastal Kenya. AIDS 2015; 29 Suppl 3: S251-9. 
70. 
Holzemer WL, Uys LR, Chirwa ML, et al. Validation of the HIV/AIDS Stigma Instrument—PLWA (HASI-P). AIDS 
Care 2007; 19(8): 1002-12. 
71. 
Omoro SA, Fann JR, Weymuller EA, Macharia IM, Yueh B. Swahili translation and validation of the Patient Health 
Questionnaire-9 depression scale in the Kenyan head and neck cancer patient population. Int J Psychiatry Med 
2006; 36(3): 367-81. 
72. 
Monahan PO, Shacham E, Reece M, et al. Validity/reliability of PHQ-9 and PHQ-2 depression scales among adults 
living with HIV/AIDS in western Kenya. J Gen Intern Med 2009; 24(2): 189-97. 
73. 
Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and 
development of a theoretical framework. BMC Health Serv Res 2017; 17(1): 88. 

43 
Version 1.1, dated 10 June 2024  
 
74. 
Saldana L, Chamberlain P, Bradford WD, Campbell M, Landsverk J. The Cost of Implementing New Strategies 
(COINS): A Method for Mapping Implementation Resources Using the Stages of Implementation Completion. 
Child Youth Serv Rev 2014; 39: 177-82. 
75. 
Saldana L, Ritzwoller DP, Campbell M, Block EP. Using economic evaluations in implementation science to 
increase transparency in costs and outcomes for organizational decision-makers. Implement Sci Commun 2022; 
3(1): 40. 
76. 
Jenness SM, Weiss KM, Goodreau SM, et al. Incidence of Gonorrhea and Chlamydia Following Human 
Immunodeficiency Virus Preexposure Prophylaxis Among Men Who Have Sex With Men: A Modeling Study. Clin 
Infect Dis 2017; 65(5): 712-8. 
77. 
Krivitsky 
PN, 
Handcock 
MS, 
Hunter 
DR, 
et 
al. 
Statnet. 
https://cran.r-
project.org/web/packages/tergm/index.html; 2015. 
78. 
Jenness SM, Goodreau SM, Morris M. EpiModel: An R Package for Mathematical Modeling of Infectious Disease 
over Networks. J Stat Softw 2018; 84. 
79. 
Kenya Demographic and Health Survey 2022. Key Indicators Report. Nairobi, Kenya: Kenya National Bureau of 
Statistics; 2023.. 
80. 
Kenya National AIDS Strategic Plan III: 2009/10 – 2012/13. Nairobi, Kenya: Government of Kenya; 2013.. 
81. 
Salomon JA, Vos T, Hogan DR, et al. Common values in assessing health outcomes from disease and injury: 
disability weights measurement study for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 
2129-43. 
82. 
Woods B, Revill P, Sculpher M, Claxton K. Country-Level Cost-Effectiveness Thresholds: Initial Estimates and the 
Need for Further Research. Value Health 2016; 19(8): 929-35. 
83. 
Mburu G, Ram M, Siu G, Bitira D, Skovdal M, Holland P. Intersectionality of HIV stigma and masculinity in eastern 
Uganda: implications for involving men in HIV programmes. BMC public health 2014 2014 Oct 11; 14: 1061. 
84. 
Van Dijck C, Laumen J, Zlotorzynska M, Manoharan-Basil SS, Kenyon C. Association between STI screening 
intensity in men who have sex with men and gonococcal susceptibility in 21 States in the USA: an ecological 
study. Sex Transm Infect 2020; 96(7): 537-40. 
85. 
Kenyon C, Laumen J, Van Dijck C. Could Intensive Screening for Gonorrhea/Chlamydia in Preexposure Prophylaxis 
Cohorts Select for Resistance? Historical Lessons From a Mass Treatment Campaign in Greenland. Sex Transm 
Dis 2020; 47(1): 24-7. 
86. 
Chisholm SA, Dave J, Ison CA. High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a 
single point mutation in the 23S rRNA genes. Antimicrob Agents Chemother 2010; 54(9): 3812-6. 
87. 
Wind CM, de Vries E, Schim van der Loeff MF, et al. Decreased Azithromycin Susceptibility of Neisseria 
gonorrhoeae Isolates in Patients Recently Treated with Azithromycin. Clin Infect Dis 2017; 65(1): 37-45. 
88. 
Gonococcal Isolate Surveillance Project (GISP).  (accessed September 30, 2021 2021). 
89. 
Weston EJ, Kirkcaldy RD, Stenger M, Llata E, Hoots B, Torrone EA. Narrative Review: Assessment of Neisseria 
gonorrhoeae Infections Among Men Who Have Sex With Men in National and Sentinel Surveillance Systems in 
the United States. Sex Transm Dis 2018; 45(4): 243-9. 
90. 
Rowlinson E, Golden MR, Berzkalns A, Thibault C, Barbee LA. Epidemiologic Treatment for Contacts to Neisseria 
gonorrhoeae and Chlamydia trachomatis Infection in Sexually Transmitted Disease Clinic Patients in Seattle, WA; 
1994 to 2018. Sex Transm Dis 2020; 47(10): 665-71. 
91. 
Graham SM, Krieger JN, Githua PL, et al. Post-prostatic massage fluid/urine as an alternative to semen for 
studying male genitourinary HIV-1 shedding. Sex Transm Infect 2011; 87(3): 232-7. 
92. 
Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global 
prevalence and incidence estimates, 2016. Bull World Health Organ 2019; 97(8): 548-62P. 
93. 
Steen R, Elvira Wi T, Kamali A, Ndowa F. Control of sexually transmitted infections and prevention of HIV 
transmission: mending a fractured paradigm. Bulletin of the World Health Organization 2009; 87(11): 858-65. 
94. 
Terris-Prestholt F, Vyas S, Kumaranayake L, Mayaud P, Watts C. The costs of treating curable sexually transmitted 
infections in low- and middle-income countries: a systematic review. Sex Transm Dis 2006; 33(10 Suppl): S153-
66. 
95. 
Centers for Disease Control and Prevention. Sexually Transmitted Infections in Developing Countries: Current 
Concepts and Strategies on Imporving STI Prevention, Treatment, and Control. Center for Disease Control 2008. 
96. 
Paavonen J, Eggert-Kruse W. Chlamydia trachomatis: impact on human reproduction. Hum Reprod Update 1999; 
5(5): 433-47. 
97. 
Ville Y, Leruez M, Glowaczower E, Robertson JN, Ward ME. The role of Chlamydia trachomatis and Neisseria 
gonorrhoeae in the aetiology of ectopic pregnancy in Gabon. Br J Obstet Gynaecol 1991; 98(12): 1260-6. 
98. 
Stephens AJ, Aubuchon M, Schust DJ. Antichlamydial antibodies, human fertility, and pregnancy wastage. Infect 
Dis Obstet Gynecol 2011; 2011: 525182. 
99. 
Amornkul PN, Vandenhoudt H, Nasokho P, et al. HIV prevalence and associated risk factors among individuals 
aged 13-34 years in Rural Western Kenya. PLoS One 2009; 4(7): e6470. 
100. 
Masese L, Baeten JM, Richardson BA, et al. Changes in the contribution of genital tract infections to HIV 
acquisition among Kenyan high-risk women from 1993 to 2012. Aids 2015; 29(9): 1077-85. 
101. 
Pettifor A, Walsh J, Wilkins V, Raghunathan P. How effective is syndromic management of STDs?: A review of 
current studies. Sex Transm Dis 2000; 27(7): 371-85. 

44 
Version 1.1, dated 10 June 2024  
 
102. 
World Health Organization Global Health Expenditure database. (2022, January 30). The World Bank: 
https://data.worldbank.org/indicator/SH.XPD.CHEX.PC.CD?locations=KE. 
103. 
World Health Organization. WHO implementation tool for pre-exposure prophylaxis (PrEP) of HIV infection. 
Module 13. Integrating STI services. Geneva: World Health Organization; 2022. 
104. 
Wi TE, Ndowa FJ, Ferreyra C, et al. Diagnosing sexually transmitted infections in resource-constrained settings: 
challenges and ways forward. J Int AIDS Soc 2019; 22 Suppl 6: e25343. 
105. 
Kohli M, Medland N, Fifer H, Saunders J. BASHH updated position statement on doxycycline as prophylaxis for 
sexually transmitted infections. Sex Transm Infect 2022; 98(3): 235-6. 
106. 
Sanders EJ, Wahome E, Okuku HS, et al. Evaluation of WHO screening algorithm for the presumptive treatment 
of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sex Transm Infect 2014; 
90(2): 94-9. 
107. 
Steen R, Dallabetta G. The use of epidemiologic mass treatment and syndrome management for sexually 
transmitted disease control. Sex Transm Dis 1999; 26(4 Suppl): S12-20; discussion S1-2. 
108. 
Steen R, Dallabetta G. Sexually transmitted infection control with sex workers: regular screening and 
presumptive treatment augment efforts to reduce risk and vulnerability. Reprod Health Matters 2003; 11(22): 
74-90. 
109. 
Fonck K, Kaul R, Kimani J, et al. A randomized, placebo-controlled trial of monthly azithromycin prophylaxis to 
prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline findings. Int 
J STD AIDS 2000; 11(12): 804-11. 
110. 
Kaul R, Kimani J, Nagelkerke NJ, et al. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted 
infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA 2004; 291(21): 2555-
62. 
111. 
Wi T, Ramos ER, Steen R, et al. STI declines among sex workers and clients following outreach, one time 
presumptive treatment, and regular screening of sex workers in the Philippines. Sex Transm Infect 2006; 82(5): 
386-91. 
112. 
Steen R, Dallabetta G, Neilsen G. Antibiotic chemoprophylaxis and HIV infection in Kenyan sex workers. JAMA 
2004; 292(8): 921; author reply -2. 
113. 
Steen R, Chersich M, Gerbase A, et al. Periodic presumptive treatment of curable sexually transmitted infections 
among sex workers: a systematic review. Aids 2012; 26(4): 437-45. 
114. 
Klausner JD, Aplasca MR, Mesola VP, Bolan G, Whittington WL, Holmes KK. Correlates of gonococcal infection 
and of antimicrobial-resistant Neisseria gonorrhoeae among female sex workers, Republic of the Philippines, 
1996-1997. J Infect Dis 1999; 179(3): 729-33. 
115. 
Kularatne R, Maseko V, Gumede L, Kufa T. Trends in Neisseria gonorrhoeae Antimicrobial Resistance over a Ten-
Year Surveillance Period, Johannesburg, South Africa, 2008(-)2017. Antibiotics (Basel) 2018; 7(3). 
116. 
Wi T, Lahra MM, Ndowa F, et al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a 
call for international collaborative action. PLoS Med 2017; 14(7): e1002344. 
117. 
Soge OO, Salipante SJ, No D, Duffy E, Roberts MC. In Vitro Activity of Delafloxacin against Clinical Neisseria 
gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance. Antimicrob Agents Chemother 2016; 
60(5): 3106-11. 
118. 
Lagace-Wiens PR, Duncan S, Kimani J, et al. Emergence of fluoroquinolone resistance in Neisseria gonorrhoeae 
isolates from four clinics in three regions of Kenya. Sex Transm Dis 2012; 39(5): 332-4. 
119. 
Lahra MM, Ryder N, Whiley DM. A new multidrug-resistant strain of Neisseria gonorrhoeae in Australia. N Engl 
J Med 2014; 371(19): 1850-1. 
120. 
Mehta SD, Maclean I, Ndinya-Achola JO, et al. Emergence of quinolone resistance and cephalosporin MIC creep 
in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009. Antimicrob 
Agents Chemother 2011; 55(8): 3882-8. 
121. 
Fayemiwo SA, Müller EE, Gumede L, Lewis DA. Plasmid-mediated penicillin and tetracycline resistance among 
Neisseria gonorrhoeae isolates in South Africa: prevalence, detection and typing using a novel molecular assay. 
Sex Transm Dis 2011; 38(4): 329-33. 
122. 
Duncan S, Thiong'o AN, Macharia M, et al. High prevalence of quinolone resistance in Neisseria gonorrhoeae in 
coastal Kenya. Sex Transm Infect 2011; 87(3): 231. 
123. 
La Ruche G, Goubard A, Bercot B, Cambau E, Semaille C, Sednaoui P. Gonococcal infections and emergence of 
gonococcal decreased susceptibility to cephalosporins in France, 2001 to 2012. Euro Surveill 2014; 19(34). 
124. 
Kimani M, van der Elst EM, Chiro O, et al. PrEP interest and HIV-1 incidence among MSM and transgender women 
in coastal Kenya. J Int AIDS Soc 2019; 22(6): e25323. 
125. 
Ngetsa CJ, Heymann MW, Thiong'o A, et al. Rectal gonorrhoea and chlamydia among men who have sex with 
men in coastal Kenya. Wellcome Open Res 2019; 4: 79. 
126. 
Dijkstra M, Mohamed K, Kigoro A, et al. Peer Mobilization and Human Immunodeficiency Virus (HIV) Partner 
Notification Services Among Gay, Bisexual, and Other Men Who Have Sex With Men and Transgender Women 
in Coastal Kenya Identified a High Number of Undiagnosed HIV Infections. Open forum infectious diseases 2021; 
8(6): ofab219. 

45 
Version 1.1, dated 10 June 2024  
 
127. 
Kunzweiler C, Bailey RC, Okall DO, et al. Enrolment characteristics associated with retention among HIV negative 
Kenyan gay, bisexual and other men who have sex with men enrolled in the Anza Mapema cohort study. J Int 
AIDS Soc 2020; 23 Suppl 6: e25598. 
128. 
Wahome EW, Graham SM, Thiong'o AN, et al. Risk factors for loss to follow-up among at-risk HIV negative men 
who have sex with men participating in a research cohort with access to pre-exposure prophylaxis in coastal 
Kenya. J Int AIDS Soc 2020; 23 Suppl 6: e25593. 
129. 
Wahome EW, Graham SM, Thiong'o AN, et al. PrEP uptake and adherence in relation to HIV-1 incidence among 
Kenyan men who have sex with men. EClinicalMedicine 2020; 26: 100541. 
130. 
Graham SM, Micheni M, Kombo B, et al. Development and pilot testing of an intervention to promote care 
engagement and adherence among HIV-positive Kenyan MSM. AIDS 2015; 29 Suppl 3: S241-9. 
131. 
Graham SM, Micheni M, Secor A, et al. HIV care engagement and ART adherence among Kenyan gay, bisexual, 
and other men who have sex with men: a multi-level model informed by qualitative research. AIDS Care 2018; 
30(sup5): S97-S105. 
132. 
Graham SM, Micheni M, Chirro O, et al. A Randomized Controlled Trial of the Shikamana Intervention to Promote 
Antiretroviral Therapy Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kenya: 
Feasibility, Acceptability, Safety and Initial Effect Size. AIDS Behav 2020. 
133. 
Kunzweiler CP, Bailey RC, Okall DO, Graham SM, Mehta SD, Otieno FO. Depressive Symptoms, Alcohol and Drug 
Use, and Physical and Sexual Abuse Among Men Who Have Sex with Men in Kisumu, Kenya: The Anza Mapema 
Study. AIDS Behav 2018; 22(5): 1517-29. 
134. 
Korhonen C, Kimani M, Wahome E, et al. Depressive symptoms and problematic alcohol and other substance 
use in 1476 gay, bisexual, and other MSM at three research sites in Kenya. AIDS 2018; 32(11): 1507-15. 
135. 
Goodreau SM, Carnegie NB, Vittinghoff E, et al. What drives the US and Peruvian HIV epidemics in men who 
have sex with men (MSM)? PLoS One 2012; 7(11): e50522. 
136. 
Goodreau SM, Hamilton DT, Jenness SM, et al. Targeting Human Immunodeficiency Virus Pre-Exposure 
Prophylaxis to Adolescent Sexual Minority Males in Higher Prevalence Areas of the United States: A Modeling 
Study. J Adolesc Health 2018; 62(3): 311-9. 
137. 
Hamilton DT, Rosenberg ES, Jenness SM, et al. Modeling the joint effects of adolescent and adult PrEP for sexual 
minority males in the United States. PLoS One 2019; 14(5): e0217315. 
138. 
Luo W, Katz DA, Hamilton DT, et al. Development of an Agent-Based Model to Investigate the Impact of HIV Self-
Testing Programs on Men Who Have Sex With Men in Atlanta and Seattle. JMIR Public Health Surveill 2018; 4(2): 
e58. 
139. 
Handcock MS, Hunter DR, Butts CT, et al. Statnet: Software tools for the Statistical Analysis of Network Data, . 
2003. 
140. 
Weiss KM, Jones JS, Anderson EJ, et al. Optimizing Coverage vs Frequency for Sexually Transmitted Infection 
Screening of Men Who Have Sex With Men. Open Forum Infect Dis 2019; 6(10): ofz405. 
141. 
Weiss KM, Jones JS, Katz DA, et al. Epidemiological Impact of Expedited Partner Therapy for Men Who Have Sex 
With Men: A Modeling Study. Sex Transm Dis 2019; 46(11): 697-705. 
142. 
Graham SM, Agutu C, van der Elst E, et al. A Novel HIV-1 RNA Testing Intervention to Detect Acute and Prevalent 
HIV Infection in Young Adults and Reduce HIV Transmission in Kenya: Protocol for a Randomized Controlled Trial. 
JMIR Res Protoc 2020; 9(8): e16198. 
143. 
Agutu CA, Oduor TH, Kombo BK, et al. High patient acceptability but low coverage of provider-initiated HIV 
testing among adult outpatients with symptoms of acute infectious illness in coastal Kenya. PLoS One 2021; 
16(2): e0246444. 
144. 
van der Elst EM, Abuna M, Agutu C, et al. "Facilitating HIV status adjustment: Qualitative insights from the 
Tambua Mapema proof-of-concept study in Kenya". PLoS One 2022; 17(1): e0261255. 
145. 
Sanders EJ, Agutu C, van der Elst E, et al. Effect of an opt-out point-of-care HIV-1 nucleic acid testing intervention 
to detect acute and prevalent HIV infection in symptomatic adult outpatients and reduce HIV transmission in 
Kenya: a randomized controlled trial. HIV Med 2021. 
146. 
Hamilton DT, Agutu C, Babigumira JB, et al. Modeling the Impact of HIV-1 Nucleic Acid Testing Among 
Symptomatic Adult Outpatients in Kenya. J Acquir Immune Defic Syndr 2022; 90(5): 553-61. 
147. 
Babigumira JB, Agutu CA, Hamilton DT, et al. Testing strategies to detect acute and prevalent HIV infection in 
adult outpatients seeking healthcare for symptoms compatible with acute HIV infection in Kenya: a cost-
effectiveness analysis. BMJ Open 2022; 12(9): e058636. 
 
 

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19. Appendices 
1) Informed Consent Documents 
a) English version 1.0, dated 20 February 2024 
b) Kiswahili version 1.0, dated 20 February 2024 
c) Dholuo version 1.0, dated 20 February 2024 
d) Translation certificates 
2) Draft study tools 
a) Screening form 
b) Participant questionnaire 
c) Exit interview topic guide 
d) Staff questionnaire 
e) Staff interview topic guide 
3) Investigator curriculum vitae 
4) Investigator ethics certificates 
5) Investigator practicing licenses 
6) Case report form 
7) UW ethical approval 
8) Insurance quotation