Bacterial sexually transmitted infections (STIs) have been on the rise among gay, bisexual, and other men who have sex with men (MSM) over the past two decades. This increase has been further accelerated by the widespread use of HIV pre-exposure prophylaxis (PrEP), which has been associated with increased sexual contact and decreased condom use. Doxycycline, a broad-spectrum tetracycline antibiotic, is being investigated as a potential prophylactic measure against these infections. A recent state-of-the-art review examined the current research, knowledge gaps, and challenges surrounding the use of doxycycline prophylaxis to prevent syphilis and other STIs.
Current Evidence on Doxycycline Prophylaxis
Doxycycline is generally well-tolerated and has been used for various infectious diseases. Several studies have examined its potential for STI prevention. A small, open-label pilot study involving 30 MSM living with HIV who had a history of syphilis found a 73% reduction (P = .02) in syphilis, gonorrhea, or chlamydia in the group receiving daily doxycycline 100 mg compared to a control group. Sexual behaviors were reported to be similar in both groups.
An open-label extension of the ANRS IPERGAY HIV-prevention study examined doxycycline post-exposure prophylaxis (Doxy PEP) in MSM and transgender women without HIV. Participants were randomized to receive doxycycline 200 mg within 24–72 hours of condomless sexual encounters (up to 3 times per week) or no prophylaxis. The Doxy PEP group experienced a lower STI incidence (hazard ratio, 0.57; P = .014), with significant reductions in chlamydia and syphilis diagnoses. Notably, Neisseria gonorrhoeae diagnoses did not differ significantly, except for fewer urethral cases in the Doxy PEP group.
A modeling study examining the impact of Doxy PrEP on syphilis among Australian MSM estimated that if 50% of MSM used Doxy PrEP and it was 70% effective, syphilis would decrease by 50% after 12 months and 85% after 10 years.
Ongoing Research and Future Directions
Several studies are currently underway or in development to further evaluate Doxy PEP/PrEP. These include:
- The Dual Daily HIV and Syphilis PrEP (DuDHS) Study (Canada): Examining concurrent daily HIV PrEP and Doxy PrEP in MSM without HIV to assess acceptability, adherence, and tolerability.
- The Daily Doxycycline in HIV+ for Syphilis PrEP (DaDHS) Study: Evaluating Doxy PrEP in MSM living with HIV.
- The Syphilaxis Study (Australia): A single-arm study of Doxy PrEP in MSM and transgender persons to measure acceptability and effectiveness in preventing syphilis, gonorrhea, and chlamydia.
- ANRS Prevenir PrEP study (France): A substudy examining the efficacy of meningococcal type B vaccine in preventing gonorrhea infection and the use of Doxy PEP to prevent chlamydia and syphilis.
- A US study: Examining Doxy PEP effectiveness and safety/tolerability in MSM and male-to-female transgender individuals.
Key Considerations and Research Priorities
While doxycycline prophylaxis shows promise, several research priorities need to be addressed before broad recommendations can be made. These include:
- Increasing the evidence base on the efficacy of Doxy PEP/PrEP.
- Identifying target populations that would benefit most.
- Determining the optimal doxycycline formulation and regimen.
- Assessing long-term safety and the potential for antimicrobial resistance.
- Evaluating community acceptability and behavioral risk compensation.
- Conducting cost-effectiveness and modeling studies.
Consistent laboratory methods for evaluating doxycycline resistance in Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and Mycoplasma genitalium are also needed, as well as guidance on interpreting microbiome and resistome data. Addressing these research priorities will be crucial in determining the appropriateness of Doxy PEP/PrEP for preventing bacterial STIs.
