Doxy-PEP: Doxycycline After Sex to Prevent Syphilis and Chlamydia

In recent years syphilis has been rising in Thailand and around the world. I see patients who are well protected against HIV with PrEP but still get syphilis or chlamydia again and again. Doxy-PEP is a new tool that many people are interested in. But it is an antibiotic, and it has to be used by the right people in the right way, so we do not create long-term problems with drug resistance.

What is Doxy-PEP?

Doxy-PEP (doxycycline post-exposure prophylaxis) means taking a single 200 mg dose of the antibiotic doxycycline after condomless oral, anal or vaginal sex, to kill bacteria before they can establish an infection. It helps prevent syphilis, chlamydia and gonorrhea. It does nothing against HIV, herpes, HPV or other viral infections.

Evidence from research

• The DoxyPEP study (NEJM 2023), in men who have sex with men and transgender women using PrEP or living with HIV, found that it reduced bacterial STIs overall by about two thirds, cutting chlamydia and syphilis by more than 80% and gonorrhea by about half.
• DOXYVAC in France found similar results, with large reductions in chlamydia and syphilis.
• dPEP Kenya (NEJM 2023), in women using PrEP, found no reduction in STIs. Part of the reason may be inconsistent use and bacteria that were already resistant.

It reduces gonorrhea less because many gonorrhea strains in several regions, including Asia, are already resistant to tetracyclines. Read more in Gonorrhea.

Who do the latest guidelines recommend it for?

The US CDC (June 2024) recommends that men who have sex with men and transgender women who have been diagnosed with syphilis, chlamydia or gonorrhea at least once in the past 12 months be counseled about Doxy-PEP. For people in the same groups who have not had an STI but have ongoing risk, it should be considered together, case by case.

The World Health Organization (July 2026) issued a conditional recommendation that Doxy-PEP may be offered to men who have sex with men and transgender women, prioritizing those who have recently had a bacterial STI, especially syphilis, and those in networks with high incidence. It does not recommend it for other populations, or as daily pre-exposure dosing.

For women, men who have sex with women and other groups, there is not yet enough evidence. In Thailand, using Doxy-PEP is therefore a shared decision between doctor and patient, based on these international guidelines.

How it is taken

1. Take doxycycline 200 mg as a single dose (for example two 100 mg tablets together), ideally within 24 hours and no later than 72 hours after condomless sex.
2. If you have sex several times in one day, one dose is enough. Do not take more than 200 mg in 24 hours. If you have sex every day, the CDC guideline allows one dose a day.
3. Take it with a full glass of water and food, and stay sitting or standing upright for at least 30 minutes. Do not take it just before lying down to sleep, to avoid inflammation of the oesophagus.
4. Take it at least 2 hours apart from milk, antacids, calcium, iron, magnesium and zinc, because they reduce absorption.

Side effects and who should not take it

• Nausea, stomach pain, heartburn
• Sensitivity to sunlight: you burn more quickly than usual. Use sunscreen and avoid strong sun, especially in a hot country like Thailand
• Must not be used in pregnancy, or by people allergic to tetracyclines
• It can be taken with PrEP, PEP and HIV treatment. If you take other regular medicines, such as blood thinners or anti-seizure medicines, tell your doctor

Drug resistance: think it through

The main concern about Doxy-PEP is that repeated antibiotic use may:

• Increase tetracycline resistance in gonorrhea
• Increase resistance in bacteria that live on the body, such as Staphylococcus aureus in the nose and on the skin
• Change the balance of bacteria in the gut

Long-term data are still being collected. That is why international guidelines limit it to groups with clear benefit, and do not recommend broad use or buying the medicine to keep and take on your own.

What to do alongside it

• Test for STIs every 3–6 months, including throat and rectal swabs and a syphilis blood test. You can still get infected while using Doxy-PEP. See testing in 14-pathogen STI PCR testing and Syphilis.
• Prevent HIV separately with PrEP, or PEP within 72 hours, both of which can be used together with Doxy-PEP.
• Use condoms when you can, and consider the HPV vaccine and hepatitis A and B vaccines.
• If you have symptoms such as discharge, sores or a rash, come for a test straight away. Do not assume Doxy-PEP covers everything.

If you use drugs during sex or have group sex, read more about safety in Chemsex.

How the clinic can help

At Dr. Kris Clinic, I assess whether Doxy-PEP suits you by looking at your STI history, your pattern of risk and any health conditions. I explain how to take it safely, coordinate it with PrEP, and set up STI testing every 3 months, both at the clinic and online, so you get the most benefit with the least risk of resistance. English-speaking consultations are available.