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Doxycycline PEP in Europe
Paving the Way to Reduced STIs With Doxycycline PEP in Eastern Europe

Released: March 20, 2024

Milosz Parczewski
Milosz Parczewski, MD, PhD
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Key Takeaways
  • Trials of doxy-PEP presented at CROI 2024 demonstrate sustained reductions in STI frequencies in both clinical trial and real-world settings, with the most pronounced reductions in chlamydia and syphilis infections.
  • In areas where STI testing and care are less accessible, such as Central and Eastern Europe, doxy-PEP is an attractive and straightforward option for STI prevention.

In the Central and Eastern European regions, combination HIV prevention programs are still underdeveloped, resulting in delayed diagnoses and initiation of care for sexually transmitted infections (STIs). Therefore, postexposure prophylaxis (PEP) options remain an attractive concept for people at risk of sexual health issues with high transferability across global populations.

Three studies presented at CROI 2024 provide strong evidence for implementation of doxycycline PEP (doxy-PEP) for prevention of STIs.

Final Results of ANRS 174 DOXYVAC
Both the EACS and CDC guidelines include recommendations on the prophylactic use of 200 mg of doxy-PEP 24-72 hours post exposure among men who have sex with men and among transgender women. The final results of the DOXYVAC trial provided an informative update on the efficacy of both doxycycline and the meningococcal B (4CMenB) vaccine in the context of STIs.

The final data showed that, for chlamydia and syphilis, there was a compound risk reduction that was consistent with the interim analysis. The overall adjusted HR of infection was 0.17 (95% CI: 0.12-0.26; P <.0001), and it remained significant for both chlamydia (adjusted HR: 0.14; 95% CI: 0.09-0.23) and syphilis (adjusted HR: 0.21; 95% CI: 0.11-0.41) when analyzed separately.

Investigators noted a less pronounced risk reduction for gonorrhea (HR: 0.67; 95% CI: 0.52-0.87; P = .003), which may be related to increased high-level antimicrobial resistance to tetracyclines in the doxy-PEP arms of the study.

The 4CMenB vaccine was associated with modest protection from gonorrhea, but cumulative incidence was not significantly reduced (HR: 0.84; 95% CI: 0.67-1.07).

DoxyPEP Study Open-label Extension
The data on doxy-PEP were further confirmed in the open-label extension of the DoxyPEP study, which also showed a remarkable decrease in the number of chlamydia and syphilis cases following use of single-dose 200-mg doxycycline after sexual acts. There was sustained reduction of STI frequencies among individuals who continued to receive doxy-PEP in both the randomized and open-label phases of the trial. There was also a reduction in STIs among individuals who were originally randomized to receive standard of care but then newly started doxycycline in the open-label phase. The greatest reductions were noted for syphilis and chlamydia, similar to the DOXYVAC trial.

Of note, investigators observed these reductions in STI frequency despite an increase in the number of sex partners and condomless sexual acts during the open-label phase of the study.

Low rates of adverse events related to doxycycline use were noted for both studies reported above.

Clinical Implementation
Lastly, I want to discuss the results of the implementation trial conducted in San Francisco to assess the impact of doxy-PEP in a real-world setting. In this study, STI incidence was compared among individuals who initiated doxy-PEP and individuals who never started doxy-PEP. Incidence analysis was performed both before and after doxy-PEP initiation.

Among doxy-PEP users, an overall decline in incidence rate ratio (IRR) for all STIs was observed (IRR: 0.42; 95% CI: 0.24-0.74), especially for chlamydia (IRR: 0.33; 95% CI: 0.23-0.46) and syphilis (IRR: 0.22; 95% CI: 0.09-0.54). There was a numeric reduction in incidence of gonorrhea, but it was not statistically significant.

Application
In certain European settings, especially the Central and Eastern European regions, where STI testing is not readily available and stigma remains high, doxycycline-based STI PEP for men who have sex with men and for transgender women is an attractive and easily implementable preventive option.

I think healthcare professionals should proceed with caution with regard to resistance selection and loss of efficacy, especially against gonorrhea, following wider-scale implementation. Overall, however, I believe the data indicate that the benefits of using doxy-PEP outweigh the potential risks so far.

Your Thoughts?
How likely are you to recommend doxy-PEP for prevention of STIs in your patients? Leave a comment to join the discussion.