We propose to conduct research on weekly antibiotic, specifically doxyclycline, taken under the observation of trained research staff, for prevention of bacterial sexually transmitted infections (STIs) among Kenyan women. The study population will include up to sixty Kenyan women between 18 and 30 years old who are already using a medication called pre-exposure prophylaxis (PrEP) for prevention of HIV. The study will be conducted at the KEMRI-RCTP clinic at Lumumba Sub-County Hospital in Kisumu County, Kenya. The primary objectives of the study are to assess the acceptability and continued use of weekly doxycycline when given under direct observation. We will also measure rates of STIs when taking weekly doxycycline prophylaxis among HIV-uninfected Kenyan women compared with data from a similar population of participants in a recently completed study (dPEP Kenya Study) in Kisumu, Kenya. Participants will be followed for six months. Participants will receive doxycycline once-weekly dose with assistance from study staff to be taken under direct observation, and participants will have STI (chlamydia, gonorrhea, and syphilis) testing and treatment at enrollment, at month-three, and at month-six. The primary outcome is continuation of antibiotic prophylaxis, or the percentage of completed weekly doxycycline doses. Secondary outcomes include quarterly new infections with the bacterial STI, Chlamydia trachomatis. Before starting study medicine and at the final visit, all participants will have samples collected for future testing of bacteria that live in the reproductive and gastrointestinal tract and resistance to antibiotics. Hair samples will be collected at follow-up visits for future study of the amount of doxycycline in hair with once a week use of doxycycline.

African women face disproportionate risk from overlapping epidemics of HIV and bacterial sexually transmitted infections (STIs). HIV pre-exposure prophylaxis (PrEP) is emerging into a global context with unprecedented rates of curable STIs. Post-exposure prophylaxis using the antibiotic doxycycline has been proposed as a novel STI prevention strategy. The first study of doxycycline postexposure prophylaxis for cisgender women did not reduce incident STIs likely due to low use of doxycycline. The overarching goal is to assess acceptability and adherence to once-weekly doxycycline dosing to prevent STIs. We will conduct a pilot study of once-weekly doxycycline to prevent bacterial STIs among Kenyan cisgender women using PrEP for HIV prevention. Approximately 50 (up to 60) sexually active, cisgender women ages 18-30 years will be enrolled in this study and followed for six months. Participants will receive doxycycline once-weekly dose as directly observed therapy (DOT). All participants will complete STI testing (chlamydia, gonorrhea, and syphilis)at enrollment, month-three and month-six. Prior to initiating treatment and at exit visit, all participants will have samples collected for future microbiome and resistance testing. Hair samples will be collected at follow-up visits for future pharmacokinetic model development. The primary endpoint is percentage of completed weekly DOT doxycycline doses. Secondary endpoint is quarterly incident rate of Chlamydia trachomatis compared with quarterly incidence among participants assigned to standard of care in the dPEP Kenya Study.