Doxycycline for STI Pre-Exposure Prophylaxis (PrEP)
Doxycycline is not currently recommended as pre-exposure prophylaxis (PrEP) for STIs, but rather is recommended as post-exposure prophylaxis (PEP) for specific high-risk populations. 1, 2
Current CDC Recommendations
- The CDC specifically recommends doxycycline as post-exposure prophylaxis (doxy PEP), not as pre-exposure prophylaxis (PrEP) 1, 2
- Doxy PEP is recommended for gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) who have had at least one bacterial STI in the past 12 months 3, 4
- The recommended dosage is 200 mg taken as a single dose within 72 hours after sexual contact, not exceeding 200 mg per 24 hours 2, 3
- Doxy PEP reduces syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50% 2, 3
Evidence for Doxycycline as PrEP vs. PEP
- A 2015 study examined doxycycline as daily PrEP (100 mg daily) among 30 MSM with HIV and found a 73% reduction in bacterial STI incidence at 48 weeks, with decreases in chlamydia and syphilis but not gonorrhea 1
- Since then, research has focused on doxy PEP rather than PrEP, with three large randomized controlled trials demonstrating significant reductions in bacterial STI acquisition with post-exposure use 1
- A 2025 systematic review and meta-analysis found that while doxy PEP might reduce first STI occurrence (particularly chlamydia), only one study evaluated doxy PrEP, making evidence insufficient for PrEP recommendations 5
Population Considerations
- Current evidence supports doxy PEP primarily for MSM and TGW with recent STI history 3, 4
- Evidence is insufficient to recommend doxy PEP or PrEP for other populations 4
- A 2025 study of female sex workers using doxy PrEP (100 mg daily) showed significant reduction in overall STI incidence without affecting vaginal flora, suggesting potential benefit in this high-risk population, but more research is needed 6
Implementation Considerations
- Doxy PEP should be implemented alongside comprehensive sexual health approaches, including regular STI screening every 3-6 months 3
- Patients should be counseled that doxy PEP/PrEP does not provide comprehensive protection against all STIs 2
- Common side effects include photosensitivity, gastrointestinal symptoms, and esophageal erosion/ulceration 1, 4
- Doxycycline should be taken on a full stomach with a full glass of liquid, and patients should avoid lying down for at least 1 hour after taking it 4
- The medication should be separated by at least 2 hours from dairy products, antacids, and supplements containing calcium, iron, magnesium, or sodium bicarbonate 4
Antimicrobial Resistance Concerns
- Some countries have recommended against widespread use of doxy PEP due to concerns about antimicrobial resistance 1
- Ongoing monitoring for antimicrobial resistance is essential as doxy PEP/PrEP use expands 7
- Prescribing strategies that target individuals with STI history, particularly those with concurrent or repeated STIs, could maximize impact while minimizing antibiotic use 8