Comparison of Weekly Versus Event-Driven Doxycycline Post-Exposure Prophylaxis for the Prevention of Sexually Transmitted Infections in MSM and TGW Receiving HIV-PrEP

The primary objective is to evaluate the non-inferiority of weekly doxycycline post-exposure prophylaxis (W-DoxyPEP) compared to event-driven prophylaxis (ED-DoxyPEP) regarding the incidence rates of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum among men who have sex with men and transgender women receiving pre-exposure prophylaxis for HIV. Secondary objectives include:

• Assessment of the incidence of symptomatic and total infections for sexually transmitted infections.
• Comparison of antimicrobial consumption involving tetracyclines, macrolides, cephalosporins, and penicillins.
• Evaluation of antimicrobial susceptibility in commensal Neisseria species, oral streptococci, and E. coli.
• Investigation of tetracycline resistance within N. gonorrhoeae isolates.
• Analysis of user experiences and perceptions.
• Evaluation of the cost-effectiveness of the two dosing regimens.

The sponsor did not provide information regarding the total number of participants. The study population consists of healthy volunteers who are HIV-negative and aged between 18 and 45 years. Eligible individuals include those assigned male sex at birth who identify as men who have sex with men or transgender women and are currently enrolled in pre-exposure prophylaxis care. Participants must be able to provide informed consent in English or Dutch. A key inclusion requirement involves a history of condomless anal sex with at least one non-steady partner within the preceding year. The research aims to evaluate the incidence rates of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum infections.

This open-label, randomized, controlled, cross-over clinical trial evaluates the efficacy of weekly doxycycline post-exposure prophylaxis (doxyPEP) compared to event-driven doxyPEP for the prevention of sexually transmitted infections. The study focuses on the incidence rates of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum among men who have sex with men and transgender women currently receiving HIV pre-exposure prophylaxis (PrEP). The research methodology aims to determine if weekly administration is non-inferior to event-driven administration in reducing bacterial infections. The trial is expected to be conducted between May 2026 and April 2028.

The experimental medication consists of doxycycline administered as a tablet. Two specific formulations are utilized: Doxycycline Sandoz 100 mg and Doxycycline EG 200 mg. The specified dosage is 200 mg, which is administered via the oral route. The study evaluates two different administration protocols: weekly dosing and event-driven dosing for the purpose of post-exposure prophylaxis against sexually transmitted infections.

The primary efficacy assessment is based on the incidence rate ratio of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum infections comparing weekly doxycycline post-exposure prophylaxis (W-DoxyPEP) to event-driven post-exposure prophylaxis (ED-DoxyPEP).

Secondary endpoints include:

• The rate ratio of tetracyclines, macrolides, cephalosporins, and penicillins.
• The minimum inhibitory concentration (MIC) distribution of cefixime, ciprofloxacin, and doxycycline for commensal Neisseria spp., oral streptococci, and E. coli.
• The incidence rate ratio of symptomatic infections for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum.
• The incidence rate ratio of all infections for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum.
• The tetracycline MIC distribution of Neisseria gonorrhoeae isolates.
• Participant perception, experience, preference, and acceptability regarding doxyPEP use.
• The incremental cost per sexually transmitted infection avoided and quality-adjusted life years (QALY) gained.