The Centers for Disease Control and Prevention (CDC) has updated its clinical guidelines regarding the use of doxycycline as post-exposure prophylaxis (doxy PEP) to prevent bacterial sexually transmitted infections (STIs). The updated guidelines recommend that healthcare providers counsel gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) with a history of at least one bacterial STI (syphilis, chlamydia, or gonorrhea) within the past 12 months about the benefits and harms of using doxy PEP. This recommendation aims to address the rising rates of STIs and provide an additional prevention strategy for high-risk individuals.
Doxy PEP involves taking a 200 mg dose of doxycycline orally within 72 hours after sexual activity. The CDC emphasizes that doxy PEP should be implemented as part of a comprehensive sexual health approach, including risk reduction counseling, regular STI screening and treatment, recommended vaccinations, and linkage to HIV pre-exposure prophylaxis (PrEP) or care services.
Efficacy of Doxy PEP
Clinical trials have demonstrated the efficacy of doxy PEP in reducing the incidence of bacterial STIs. Key findings from these studies include:
- IPERGAY Study: A French study found a 70% reduction in chlamydia and a 73% reduction in syphilis among HIV-negative MSM and TGW taking tenofovir disoproxil fumarate and emtricitabine as PrEP who used doxy PEP.
- DoxyPEP Study: A randomized trial in San Francisco and Seattle showed significant reductions in gonorrhea (45% reduction in PrEP users, 43% reduction in those with HIV), chlamydia (88% and 74% reduction, respectively), and early syphilis (87% and 77% reduction, respectively) among MSM and TGW.
- ANRS DOXYVAC Study: This French trial reported significant reductions in gonorrhea (adjusted hazard ratio [aHR]: 0.49; 95% CI = 0.32–0.76), chlamydia (aHR: 0.11; 95% CI = 0.04–0.30), and syphilis (aHR: 0.21; 95% CI = 0.09–0.47) with doxy PEP.
However, a study among cisgender women in Kenya did not find a significant reduction in bacterial STIs. The CDC notes that low adherence to the doxycycline regimen may have contributed to the lack of efficacy in this population, and further research is needed to explore potential biological differences.
Potential Harms and Considerations
While doxy PEP has shown promise in reducing STI rates, potential harms and considerations include:
- Antimicrobial Resistance: There is concern that widespread use of doxycycline could lead to increased antimicrobial resistance in both STIs and other common bacterial pathogens. Data from the DoxyPEP study showed an increase in tetracycline-resistant Staphylococcus aureus among participants in the doxy PEP arm.
- Adverse Events: Clinical trials have reported gastrointestinal side effects as the most common adverse event associated with doxy PEP. A meta-analysis of longer-term doxycycline use found an increased risk of gastrointestinal or dermatological adverse events compared to placebo.
The CDC emphasizes the need for ongoing monitoring of antimicrobial resistance patterns and further research to assess the long-term effects of intermittent doxycycline use on the microbiome and the development of resistance.
Recommendations for Implementation
The CDC recommends the following for implementing doxy PEP:
- Target Population: Providers should counsel MSM and TGW with a history of at least one bacterial STI in the past 12 months about doxy PEP.
- Dosage and Administration: If prescribed, the recommended dose is 200 mg of doxycycline taken within 72 hours after sexual activity, with a maximum dose of 200 mg every 24 hours.
- Comprehensive Approach: Doxy PEP should be part of a comprehensive sexual health strategy, including risk reduction counseling, STI screening, and vaccination.
- Regular Monitoring: Persons prescribed doxy PEP should undergo bacterial STI testing at baseline and every 3–6 months thereafter.
The CDC acknowledges that clinical data supporting doxy PEP in other populations, such as cisgender women and heterosexual men, are limited. Providers should use their clinical judgment and shared decision-making to inform the use of doxy PEP in these populations.
These updated guidelines reflect the CDC's commitment to addressing the STI epidemic through innovative prevention strategies while carefully considering potential risks and benefits.
