Doxycycline post-exposure prophylaxis (DoxyPEP) is emerging as a promising strategy for preventing bacterial sexually transmitted infections (STIs) among high-risk populations. Recent studies and real-world data indicate its effectiveness, particularly against syphilis and chlamydia, but concerns remain regarding antimicrobial resistance and the need for further research in diverse populations.
Efficacy of DoxyPEP in Clinical Trials
Several randomized controlled trials have demonstrated the efficacy of doxyPEP. A French trial involving gay and bisexual men on HIV PrEP found a 70% reduction in chlamydia infections and a 73% reduction in syphilis infections among those taking doxycycline after sex. However, the antibiotic had no significant effect on gonorrhea, likely due to high rates of tetracycline resistance in the region.
The US DoxyPEP study reported a 66% reduction in the incidence of all STIs per quarter in both people living with HIV and those taking HIV PrEP. Doxycycline was effective against chlamydia, syphilis, and gonorrhea in this study. The Doxyvac study also found significant reductions in chlamydia and syphilis, with a more modest reduction in gonorrhea incidence.
However, the dPEP Kenya trial, the only study done with cisgender women, found that doxyPEP did not prevent bacterial STIs among women taking HIV PrEP. Poor adherence to the regimen was identified as a potential factor in the lack of efficacy.
Real-World Implementation and Impact
San Francisco was the first city to recommend doxyPEP in 2022. Data from the San Francisco AIDS Foundation's Magnet sexual health clinic showed a 58% reduction in overall STI incidence among PrEP users who opted to take doxyPEP. Chlamydia and syphilis cases saw the most significant reductions, while gonorrhea cases remained relatively unchanged.
Population-level trends in San Francisco revealed a marked decrease in chlamydia and syphilis cases among gay and bisexual men and trans women after doxyPEP implementation. Conversely, new chlamydia cases among cisgender women, who were not offered doxyPEP, increased during the same period.
Concerns and Guidelines
Despite the promising data, some public health agencies remain cautious about recommending widespread doxyPEP use due to concerns about the development of antimicrobial resistance. The Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) has issued a consensus statement acknowledging doxyPEP's effectiveness but urging clinicians to consider potential adverse outcomes associated with long-term use.
The US Centers for Disease Control and Prevention (CDC) issued guidelines recommending doxyPEP use for gay and bisexual men and trans women who have had a bacterial STI in the past year, with regular STI testing. However, guidelines vary across regions, reflecting differing perspectives on the balance between benefits and risks.
Potential for Resistance
Resistance to doxycycline is a significant concern, particularly for gonorrhea and chlamydia. While doxycycline is not typically used to treat gonorrhea, the emergence of resistant strains could complicate treatment efforts. Doxycycline is a first-line treatment for uncomplicated chlamydia, making the development of resistance a serious threat.
Studies have shown varying rates of doxycycline resistance in different regions. The US DoxyPEP study found a small but significant increase in doxycycline-resistant Staphylococcus aureus among participants taking the antibiotic.
Who Could Benefit?
DoxyPEP is most likely to benefit gay and bisexual men and transgender women who have had a bacterial STI in the past year or who engage in behaviors that put them at high risk for STIs, such as condomless sex and multiple sexual partners. The evidence suggests that doxyPEP is effective against syphilis and chlamydia but may be less effective against gonorrhea, depending on local resistance patterns.
Dosing and Administration
Guidelines recommend a 200mg dose of doxycycline after a sexual encounter, ideally within 24 hours and no later than 72 hours. No more than one dose should be taken every 24 hours.
Side Effects
Doxycycline is generally safe and well-tolerated. The most common side effects are gastrointestinal, such as diarrhea, vomiting, and nausea. Increased sensitivity to light can also occur with prolonged use. Doxycycline should not be used by pregnant people or those who might become pregnant.
Balancing Benefits and Risks
DoxyPEP represents a promising tool for preventing bacterial STIs among high-risk populations. However, the potential for antimicrobial resistance necessitates careful monitoring and targeted implementation. Further research is needed to assess the long-term impact of doxyPEP on resistance patterns and to evaluate its effectiveness in diverse populations, including cisgender women.
