The goal of this clinical trial is to compare the effectiveness of doxycycline taken for on-demand pre-exposure prophylaxis (DoxyODPrEP) and its post-exposure use (DoxyPEP) in preventing bacterial sexually transmitted infections (STI), including chlamydia, gonorrhoea, and syphilis among men who have sex with men (MSM). The main questions it aims to answer are:

1. Is DoxyODPrEP superior to DoxyPEP?
2. Are both regimens safe?
3. Does the MSM community accept the use of doxycycline to prevent bacterial STI?

Participants will be asked to take doxycycline according to the study arm they are randomly assigned to, and attend regular clinical follow-ups during the 2-year observation period. Researchers will compare the bacterial STI incidences between the two groups to see if DoxyODPrEP is superior to DoxyPEP.

Participants would be randomly assigned to either DoxyODPrEP or DoxyPEP arm, and be instructed to take doxycycline with the respective dosing schedule. They would be followed up for 24 months for nucleic acid amplification test (NAAT) and antibody tests against bacterial STI, namely chlamydia, gonorrhoea, and syphilis. The subjects and investigators would not be blinded due to its open-label nature, as the two arms' dosing schedules are different. Participants in the DoxyODPrEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally 2-24 hours before sex, and one 100mg capsule each 24 and 48 hours after loading dose. If they have sex within 48 hours after the loading dose, they would be asked to continue a daily 100mg until two days after the last sex. Participants in the DoxyPEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally within 24 hours and up to 72 hours after each sex. At each clinic visit, urine, and pharyngeal and rectal swabs would be self-collected on-site by the participants following instructions. Pill count would be performed for each follow-up visit.

Inclusion Criteria:

• has had sex with another male in the past six months
• normally reside in Hong Kong
• can communicate in written and spoken Chinese or English
• willing and able to give written informed consent
• being willing and able to attend scheduled study clinic visits
• at risk of STI (had condomless sex with more than one man in the past 12 months, history of STI diagnosis in the past 12 months, inclination to have condomless sex, and other HIV-PrEP-eligible criteria)

Exclusion Criteria:

• Being allergic to tetracycline class medicines
• Currently taking medications that are contraindicated with doxycycline
• Using antibiotics for more than 14 days in the month preceding enrolment