In 2024, the Centers for Disease Control and Prevention (CDC) released guidelines[1] for the recommended use of doxycycline postexposure prophylaxis (Doxy PEP) for sexually transmitted infection (STI) prevention. Postexposure prophylaxis is a chemoprophylaxis strategy where a medication is taken after a possible exposure to prevent an infection. This is a common and effective prevention strategy for HIV and other infections, such as rabies and tetanus. Doxycycline is a broad-spectrum tetracycline antibiotic that is well tolerated and is the current recommended treatment for chlamydia and an alternative treatment for syphilis in nonpregnant patients.[2] Although doxycycline is not recommended for gonorrhea treatment, owing to antimicrobial resistance, it remains effective against many strains of Neisseria gonorrhoeae in the United States.[3] Each year, millions of STIs, such as chlamydia, syphilis, and gonorrhea, are reported in the US.[4] Vaccines for these infections are not currently available, so novel prevention approaches, such as Doxy PEP, are needed. Healthcare providers should be aware of the evidence for Doxy PEP as an STI prevention strategy, which patients would benefit the most, and how to prescribe it.
1. Doxy PEP is effective in reducing the rates of STIs among certain populations.
Doxy PEP has proven to reduce the risk of getting some bacterial STIs (syphilis, chlamydia, and in some studies, gonorrhea) for gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) at increased risk for STIs. The Doxy PEP recommendations are based on clinical studies that evaluated its efficacy for reducing bacterial STIs.[5-8] These studies demonstrated a significant reduction in STIs among participants randomized to take doxycycline no later than 72 hours after sex compared to no medication prophylaxis.[5-7] Only one trial was conducted among cisgender women[8] and found no significant reduction in bacterial STIs. No significant adverse events were attributed to doxycycline[5-7] with gastrointestinal side effects being the most common event reported.
2. Providers should discuss Doxy PEP with gay, bisexual, and other MSM and TGW with a history of at least one bacterial STI (gonorrhea, chlamydia, and syphilis) in the past 12 months.
The guidelines aim to provide Doxy PEP to people who would benefit most while minimizing antimicrobial use.[1] Clinical studies on the efficacy of Doxy PEP were primarily focused on MSM and TGW with[6,7] and without HIV infection[5] and with a history of STI diagnosis within the previous 12 months.[7] In a cohort of MSM and TGW and nonbinary persons assigned male sex at birth, a modeling study demonstrated that prescribing Doxy PEP for 12 months after an STI diagnosis was the most efficient intervention strategy, averting 42% of STIs.[9] Given this, the CDC recommends that providers discuss Doxy PEP with all gay, bisexual, and other MSM and TGW with a history of at least one bacterial STI (gonorrhea, chlamydia, and syphilis) in the past 12 months.[1] Providers can also discuss Doxy PEP, utilizing a shared decision-making approach, with MSM and TGW who have not had a bacterial STI diagnosis within the previous 12 months but may be participating in sexual activities that would increase the likelihood of STIs.[1] Although experience in treating other STIs would support efficacy of Doxy PEP in other populations (ie, cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons assigned female at birth), clinical data to support use is limited and providers should use clinical judgment and shared decision-making in use of Doxy PEP in these populations.[1]
3. As appropriate, providers should write a prescription for self-administration of 200 mg of doxycycline, taken as a single dose, within 72 hours after sex, with enough doses until the next follow-up visit.
After shared decision-making with the patient, if Doxy PEP is prescribed, providers should write a prescription for self-administration of 200 mg of doxycycline taken as a single dose (any available formulation) with instructions for the patient to take it as soon as possible within 72 hours after having oral, vaginal, or anal sex.[1] Patients should not take more than 200 mg every 24 hours. On the basis of the person’s anticipated sexual activity, a prescription should provide enough doses to last until their next visit. Providers should also reassess the need for Doxy PEP at these visits, which should take place every 3-6 months.[1]
To minimize potential side effects of doxycycline, patients should be advised to take Doxy PEP with at least 8 ounces of water and food. To reduce esophageal irritation, patients should not lie down for 1 hour after taking doxycycline. Dairy products, antacids, and supplements that contain iron, calcium, and magnesium can interfere with the absorption of doxycycline, so this medication should not be taken within 2 hours of their use. Doxycycline can also cause photosensitivity, and patients should be advised to wear sunscreen or cover exposed areas to stay protected from the sun while taking the medication.[1] In a systematic review, longer-term use (≥ 8 weeks) was only found to be associated with increased risk for gastrointestinal and dermatological adverse events, consistent with known side effects of doxycycline. Serious side effects were rare.[1]
4. Doxy PEP should be offered in the context of comprehensive sexual health.
When offered, implement Doxy PEP in the context of a comprehensive sexual health approach. Providers should set up routine follow-up visits every 3-6 months for those prescribed Doxy PEP. These visits should be at intervals that align with the patient’s existing HIV and STI screening recommendations. During these visits:
5. CDC and partners continue to learn more about the effectiveness of Doxy PEP among other populations, such as cisgender women, and potential long-term concerns.
At this time, there is not enough information to assess the benefits and harms in the use of Doxy PEP in populations other than gay, bisexual, and other MSM and TGW, who are more likely to get STIs.[1] Future studies on the efficacy of Doxy PEP in other populations, including cisgender women, are important to ensure that all who benefit most are offered Doxy PEP. CDC will update the guidelines as additional data become available.
Questions also remain about potential long-term development of antimicrobial resistance in bacterial STIs and other common bacterial pathogens (eg, Staphylococcus aureus), impacts on the microbiome, and potential impacts on syphilis serologic testing with Doxy PEP use.[1] Data from the 12-month follow-up period in one study demonstrated an increase in tetracycline resistance in participants colonized with Staphylococcus aureus at baseline,[6] but more data are needed to understand long-term impacts. CDC, federal partners, and other research organizations continue to monitor for any increases in antimicrobial resistance from Doxy PEP and will update guidelines as more data become available.[1]
For more detailed clinical recommendations on the use of Doxy PEP, access the CDC Clinical Guidelines.
Disclaimer: The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the official position of the US Department of Health and Human Services, the Public Health Service, or the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the US Department of Health and Human Services or the US Centers for Disease Control and Prevention.
COMMENTARY
Doxycycline Postexposure Prophylaxis (Doxy PEP): 5 Things to Know
DISCLOSURES
| January 17, 2025Editorial Collaboration
&
In 2024, the Centers for Disease Control and Prevention (CDC) released guidelines[1] for the recommended use of doxycycline postexposure prophylaxis (Doxy PEP) for sexually transmitted infection (STI) prevention. Postexposure prophylaxis is a chemoprophylaxis strategy where a medication is taken after a possible exposure to prevent an infection. This is a common and effective prevention strategy for HIV and other infections, such as rabies and tetanus. Doxycycline is a broad-spectrum tetracycline antibiotic that is well tolerated and is the current recommended treatment for chlamydia and an alternative treatment for syphilis in nonpregnant patients.[2] Although doxycycline is not recommended for gonorrhea treatment, owing to antimicrobial resistance, it remains effective against many strains of Neisseria gonorrhoeae in the United States.[3] Each year, millions of STIs, such as chlamydia, syphilis, and gonorrhea, are reported in the US.[4] Vaccines for these infections are not currently available, so novel prevention approaches, such as Doxy PEP, are needed. Healthcare providers should be aware of the evidence for Doxy PEP as an STI prevention strategy, which patients would benefit the most, and how to prescribe it.
1. Doxy PEP is effective in reducing the rates of STIs among certain populations.
Doxy PEP has proven to reduce the risk of getting some bacterial STIs (syphilis, chlamydia, and in some studies, gonorrhea) for gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) at increased risk for STIs. The Doxy PEP recommendations are based on clinical studies that evaluated its efficacy for reducing bacterial STIs.[5-8] These studies demonstrated a significant reduction in STIs among participants randomized to take doxycycline no later than 72 hours after sex compared to no medication prophylaxis.[5-7] Only one trial was conducted among cisgender women[8] and found no significant reduction in bacterial STIs. No significant adverse events were attributed to doxycycline[5-7] with gastrointestinal side effects being the most common event reported.
2. Providers should discuss Doxy PEP with gay, bisexual, and other MSM and TGW with a history of at least one bacterial STI (gonorrhea, chlamydia, and syphilis) in the past 12 months.
The guidelines aim to provide Doxy PEP to people who would benefit most while minimizing antimicrobial use.[1] Clinical studies on the efficacy of Doxy PEP were primarily focused on MSM and TGW with[6,7] and without HIV infection[5] and with a history of STI diagnosis within the previous 12 months.[7] In a cohort of MSM and TGW and nonbinary persons assigned male sex at birth, a modeling study demonstrated that prescribing Doxy PEP for 12 months after an STI diagnosis was the most efficient intervention strategy, averting 42% of STIs.[9] Given this, the CDC recommends that providers discuss Doxy PEP with all gay, bisexual, and other MSM and TGW with a history of at least one bacterial STI (gonorrhea, chlamydia, and syphilis) in the past 12 months.[1] Providers can also discuss Doxy PEP, utilizing a shared decision-making approach, with MSM and TGW who have not had a bacterial STI diagnosis within the previous 12 months but may be participating in sexual activities that would increase the likelihood of STIs.[1] Although experience in treating other STIs would support efficacy of Doxy PEP in other populations (ie, cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons assigned female at birth), clinical data to support use is limited and providers should use clinical judgment and shared decision-making in use of Doxy PEP in these populations.[1]
3. As appropriate, providers should write a prescription for self-administration of 200 mg of doxycycline, taken as a single dose, within 72 hours after sex, with enough doses until the next follow-up visit.
After shared decision-making with the patient, if Doxy PEP is prescribed, providers should write a prescription for self-administration of 200 mg of doxycycline taken as a single dose (any available formulation) with instructions for the patient to take it as soon as possible within 72 hours after having oral, vaginal, or anal sex.[1] Patients should not take more than 200 mg every 24 hours. On the basis of the person’s anticipated sexual activity, a prescription should provide enough doses to last until their next visit. Providers should also reassess the need for Doxy PEP at these visits, which should take place every 3-6 months.[1]
To minimize potential side effects of doxycycline, patients should be advised to take Doxy PEP with at least 8 ounces of water and food. To reduce esophageal irritation, patients should not lie down for 1 hour after taking doxycycline. Dairy products, antacids, and supplements that contain iron, calcium, and magnesium can interfere with the absorption of doxycycline, so this medication should not be taken within 2 hours of their use. Doxycycline can also cause photosensitivity, and patients should be advised to wear sunscreen or cover exposed areas to stay protected from the sun while taking the medication.[1] In a systematic review, longer-term use (≥ 8 weeks) was only found to be associated with increased risk for gastrointestinal and dermatological adverse events, consistent with known side effects of doxycycline. Serious side effects were rare.[1]
4. Doxy PEP should be offered in the context of comprehensive sexual health.
When offered, implement Doxy PEP in the context of a comprehensive sexual health approach. Providers should set up routine follow-up visits every 3-6 months for those prescribed Doxy PEP. These visits should be at intervals that align with the patient’s existing HIV and STI screening recommendations. During these visits:
5. CDC and partners continue to learn more about the effectiveness of Doxy PEP among other populations, such as cisgender women, and potential long-term concerns.
At this time, there is not enough information to assess the benefits and harms in the use of Doxy PEP in populations other than gay, bisexual, and other MSM and TGW, who are more likely to get STIs.[1] Future studies on the efficacy of Doxy PEP in other populations, including cisgender women, are important to ensure that all who benefit most are offered Doxy PEP. CDC will update the guidelines as additional data become available.
Questions also remain about potential long-term development of antimicrobial resistance in bacterial STIs and other common bacterial pathogens (eg, Staphylococcus aureus), impacts on the microbiome, and potential impacts on syphilis serologic testing with Doxy PEP use.[1] Data from the 12-month follow-up period in one study demonstrated an increase in tetracycline resistance in participants colonized with Staphylococcus aureus at baseline,[6] but more data are needed to understand long-term impacts. CDC, federal partners, and other research organizations continue to monitor for any increases in antimicrobial resistance from Doxy PEP and will update guidelines as more data become available.[1]
For more detailed clinical recommendations on the use of Doxy PEP, access the CDC Clinical Guidelines.
Disclaimer: The conclusions, findings, and opinions expressed by the authors do not necessarily reflect the official position of the US Department of Health and Human Services, the Public Health Service, or the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the US Department of Health and Human Services or the US Centers for Disease Control and Prevention.
Public Information from the CDC and Medscape
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