Doxycycline as STD Prophylaxis

What is PEP?

The term “doxy-PEP” (short for “doxycycline postexposure prophylaxis”) refers to the use of the oral antibiotic doxycycline in certain patients after engaging in unprotected sex. The rationale behind this emerging medical trend is that it will help to decrease the incidence of new bacterial sexually transmitted infections (STIs), especially in patient populations that have been identified as having a disproportionately high risk of contracting such infections. 

Rates of bacterial STIs have been steadily increasing in recent years. In June 2024, The Center for Disease Control and Prevention officially made the following recommendation: “For men who have sex with men (MSM) and transgender woman (TGW) with a history of bacterial STIs in the prior 12 months or whose planned sexual activity increases exposure to STIs (e.g., having multiple or anonymous partners), we suggest doxycycline post-exposure prophylaxis to reduce the risk of chlamydia, gonorrhea, and syphilis." This advice comes after a careful review of three large randomized controlled trials demonstrated that this technique reduced syphilis and chlamydia infections by >70% and gonococcal infections by around 50%.  The timeliness of this announcement is uncanny, with rates of bacterial STIs continuing to rise and disproportionately affect gay men and transgender women. Perhaps not surprisingly, the incidence of certain serious illnesses has risen alongside increasing STI rates, including congenital syphilis and blindness as a result of untreated syphilis, increased rates of HIV transmission, and more. 

How PEP is taken:

 The CDC released clinical guidelines to help healthcare professionals optimize the implementation of this preventative strategy in their practices. After identifying your patient as someone who may benefit from this effort (i.e., an HIV+ male who has sex with men with an undetectable viral load who was diagnosed with gonorrhea this past summer), they suggest counseling the patient on the benefits and risks of doxy PEP and using shared decision-making to determine whether it should be provided. The benefit of doxy PEP is a reduction in the risk of contracting chlamydia, gonorrhea, and/or syphilis. In contrast, the risks include gastrointestinal side effects (like nausea, upset stomach, diarrhea, etc.) and, more importantly, the uncertain yet critical-to-consider risk of increasing antibiotic resistance.

The official guideline suggests taking one dose of 200 mg doxycycline within 24-72 hours after having unprotected sex, with no more than 200 mg of the drug to be taken in one 24-hour period.4 

 Who should consider doxy PEP?

The design of the studies which produced the findings described in this article regarding doxy-pep shared a critical limitation: they were only conducted on men who have sex with men (MSM) and transgender women. This demographic restriction has forced the CDC’s official guideline to explicitly state that this preventative strategy is only appropriate “for MSM and transgender women who have a history of bacterial STI in the prior 12 months or whose planned sexual activity increases exposure to STIs (i.e., multiple or anonymous partners)...to reduce the risk of chlamydia, gonorrhea, and syphilis.” Furthermore, this restriction meant that the guidance would be classified as a Class 2B recommendation, which carries less weight and decreases clinicians' enthusiasm when deciding whether or not to prescribe or recommend it. It should be noted that just because the current literature only supports the use of doxy-pep in MSM and transgender women, virtually all clinicians agree that it would likely be just as efficacious in other populations. 

The reason that MSM were specifically targeted for these studies relates to the earlier-mentioned fact that bacterial STIs affect MSM at a disproportionately higher rate than their heterosexual male counterparts. The resurgence of these infections–particularly gonorrhea and syphilis–has been linked to the availability of increasingly effective antiretroviral therapy (ART), which are medications used to treat and prevent human immunodeficiency virus (HIV) infection. In a study conducted in 2015, researchers examined over 650 MSM individuals who started taking pre-exposure prophylaxis (PrEP). The study found that although there were no new HIV infections, there was a 40 percent decrease in condom usage. Additionally, 50 percent of the participants acquired a different sexually transmitted infection (STI) within 12 months of starting PrEP. 

Conclusion

Preventing the spread of STIs has consistently presented serious challenges for clinicians throughout the history of modern medicine. While antimicrobial-based prevention strategies were the focus of this article, one should understand this topic within the larger context of STI prevention in general; thus, a discussion of STI prevention will conclude this piece. 

There are some significant strategies on which a comprehensive approach to STI prevention, as follows:

• Obtaining an accurate Sexual Health assessment that includes sexual orientation and gender identification with education and counseling on ways to avoid STIs
•  Pre-exposure vaccination for vaccine-preventable STIs
•  Identifying individuals with STIs and not overlooking asymptomatic patients
• Effectively diagnosing, treating, and following up with STI patients and their sexual partners.

A thorough discussion of each of these strategies is beyond the scope of this article and would require a separate piece, although you are encouraged to research as much as you can on your own! Also, if you are reading this and think you might be someone at higher risk for contracting bacterial STIs, don’t hesitate to initiate the discussion of starting doxy-pep with your healthcare provider. 

Written by Jay Fickle

Edited by Saranyah Kannuchamy

References

1. Bachmann LH, Barbee LA, Chan P, et al. CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024. Morbidity and mortality weekly report. 2024;73(2):1–8. doi:10.15585/mmwr.rr7302a1
2. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2018. Atlanta: US Department of Health and Human Services. 2019;10
3. Sara E Oliver, &nbsp, Mark Aubin, et al. Oliver SE, Aubin M, Atwell L, et al. Ocular Syphilis - Eight Jurisdictions, United States, 2014-2015. MMWR Morb Mortal Wkly Rep. 2016;65(43):1185-1188. Published 2016 Nov 4. doi:10.15585/mmwr.mm6543a2. MMWR: Morbidity and Mortality Report. 2016;65(43):1185–1188. doi:10.15585/mmwr.mm6543a2.
4. Mayer KH, de Vries H. HIV and sexually transmitted infections: responding to the "newest normal.". Journal of the International AIDS Society. 2018;21(7). doi:10.1002/jia2.25164