Randomized Trial of Doxycycline Post‑Exposure Prophylaxis for STI Prevention and MRSA Colonization in MSM and Transgender Women on Antiretroviral Therapy

The primary objective is to evaluate the effect of doxycycline post‑exposure prophylaxis (doxyPEP) on three clinically relevant outcomes in men who have sex with men and transgender women: the incidence of nasal colonization by Staphylococcus aureus with resistance mechanisms, the overall incidence of sexually transmitted infections, and alterations in gut microbiota composition following initiation of doxyPEP. Secondary objectives include:

• Comparison of the incidence of colonization with doxycycline‑resistant Staphylococcus aureus between the doxyPEP and control arms at baseline, 6 months, and 12 months.
• Characterization of resistance mechanisms among S. aureus colonizers in both groups using whole‑genome sequencing.
• Assessment of differences in gut microbiota composition between participants receiving doxyPEP and those not receiving prophylaxis at baseline and after one year.
• Investigation of the emergence of mobile genetic elements harboring antimicrobial‑resistance genes in the gut microbiota following doxyPEP exposure.
• Determination of the incidence of infections caused by Treponema pallidum, Chlamydia trachomatis, and Neisseria gonorrhoeae in the doxyPEP versus control groups.
• Evaluation of the incidence of doxycycline‑resistant C. trachomatis infections between the two study arms.
• Documentation of participants with at least one bacterial STI in the preceding year.
• Inclusion of participants who are PrEP users on active prophylaxis for ≥3 months, or people living with HIV on antiretroviral therapy for ≥3 months with an undetectable viral load.

The trial enrolled adult individuals (≥ 18 years) identified as men who have sex with men or transgender women, including users of pre‑exposure prophylaxis and people living with HIV, all of whom were male according to the sponsor’s classification. Selection was based on documented risk factors for sexually transmitted infections, such as having more than ten sexual partners in the preceding year, at least one episode of condomless anal intercourse, drug use associated with unprotected sex, and prior receipt of post‑exposure prophylaxis on multiple occasions; informed consent was required. Participants were generally in good health aside from their HIV or PrEP status and were assessed for colonization by methicillin-resistant Staphylococcus aureus and gut microbiota composition. Lifestyle considerations included a high‑risk sexual behavior profile and substance use relevant to transmission risk. The sponsor did not provide information regarding the total number of participants enrolled in the study.

The study is a multicenter, randomized, open‑label, controlled, parallel‑group trial enrolling adult men who have sex with men and transgender women who are PrEP users or living with HIV and meet predefined STI risk criteria. Participants are allocated to receive either the test product doxycycline (200 mg orally) or one of several standard antiretroviral regimens used as comparators. The trial period spans from the planned recruitment start on 29 June 2026 to an estimated completion date of 1 June 2029, with each participant followed for approximately 12 months. After providing informed consent, subjects attend a screening visit to verify eligibility, followed by a baseline visit where randomization occurs and the assigned medication is initiated. Subsequent study visits are scheduled at predetermined intervals to monitor safety, assess adherence, and collect specimens for the primary endpoint—prevalence of nasal colonization by doxycycline‑resistant Staphylococcus aureus—as well as secondary assessments of gut microbiota composition, antimicrobial resistance, and incidence of bacterial STIs. The final visit at month 12 serves as the end‑of‑study assessment, completing data collection for all primary and secondary outcomes.

The investigational product is a combination oral formulation containing doxycycline 200 mg and ambroxol hydrochloride, supplied as a film‑coated tablet (PHF00209MIG). The assigned dose is 200 mg per administration, delivered orally; the dosing schedule and frequency are defined by the trial protocol and adherence is monitored through pill counts and participant diaries.

One comparator regimen consists of Dovato 50 mg/300 mg film‑coated tablets, administered orally. Each tablet provides the fixed‑dose combination of lamivudine and dolutegravir in the indicated strengths.

Another comparator regimen is Biktarvy 30 mg/120 mg/15 mg film‑coated tablets, taken orally. The tablet contains emtricitabine, tenofovir alafenamide, and bictegravir at the specified dosages.

Juluca 50 mg/25 mg film‑coated tablets are provided as an oral comparator, delivering a fixed‑dose combination of rilpivirine and dolutegravir.

Triumeq 50 mg/600 mg/300 mg film‑coated tablets are administered orally and comprise abacavir, lamivudine, and dolutegravir in a single tablet.

Odefsey 200 mg/25 mg/25 mg film‑coated tablets are given orally and contain emtricitabine, tenofovir alafenamide, and rilpivirine.

Tenofovir disoproxil and emtricitabine are supplied as an oral fixed‑dose combination tablet (PHF00082MIG) with a total dose of 200 mg of the combined active ingredients.

The primary efficacy assessment is the prevalence of nasal colonization by doxycycline‑resistant Staphylococcus aureus*​*, determined through collection of nasal specimens and subsequent microbiological analysis to identify resistant strains.