‘Doxy PEP’ trials show promise for preventing some sexually transmitted infections

Sexually transmitted infections (STIs) are on the rise in many places. We report on the growing evidence about one possible bacterial STI prevention tool: doxy PEP. 

What is the research about? 

The use of the antimicrobial drug doxycycline to prevent syphilis, chlamydia and gonorrhoea. 

In the USA, randomised control trials of doxycycline post-exposure prophylaxis (doxy PEP) have been done with transgender women and gay, bisexual and other men who have sex with men. Other doxy PEP trials have been done in France and Kenya. 

Why is this research important? 

Every day around the world, one million people get an STI, and rates are increasing in many countries. STIs can cause painful and uncomfortable symptoms. Some increase the risk of HIV, cancer, infertility and pregnancy complications. 

Doxycycline is already used to treat chlamydia and syphilis. And it is already used to prevent non-STIs infections like malaria and Lyme disease. But until recently the use of doxycycline to prevent bacterial STIs has not been studied. 

What did they find out? 

In 2022, a randomised trial called DoxyPEP took place in the USA. This involved around 500 transgender women and men who have sex with men. Most participants (327) were HIV-negative and taking PrEP to prevent HIV. The rest of the participants had HIV and were on treatment. All reported having condomless sex with at least one man and one or more STI in the past 12 months. 

Participants were given doxy PEP to take, ideally within 24 hours but no later than 72 hours after condomless sex (anal, oral or vaginal). Participants were advised to take no more than one doxy PEP dose every 24 hours.  

The trial found doxy PEP reduced the risk of chlamydia and syphilis infection by more than 70% and gonorrhoea by around 55%. Adherence was good, with around 70% of participants always taking doxy PEP within 72 hours after condomless sex. 

A trial in France in 2022 (the DOXYVAC study) with men who have sex with men also found that doxy PEP reduced chlamydia and syphilis infections by more than 70%. But it found doxy PEP only reduced the risk of gonorrhoea by 33%. An older French trial (IPERGAY) conducted between 2015 and 2016 found doxy PEP reduced the risk of chlamydia and syphilis infection by around 70%, but it did not reduce the risk of gonorrhoea. 

In Kenya, a doxy PEP trial was conducted with 450 cisgender women between 2020 and 2022. It found doxy PEP did not significantly reduce chlamydia or gonorrhoea. Hair studies detected doxy PEP in only 29% of participants, suggesting that non-adherence might have been an issue. However, biological causes still need to be explored. Its impact on syphilis could not be evaluated due to a lack of syphilis infections. 

No serious side effects from doxy PEP were reported in the trials. Mild to moderate side effects included stomach and skin irritation. 

There are concerns that doxy PEP could lead to people developing resistance to treatment for bacterial infections, including bacterial STIs. Research so far suggests that doxy PEP does not lead to chlamydia or syphilis becoming resistant to doxycycline treatment. But there are particular concerns about the use of doxy PEP causing resistance to some types of gonorrhoea treatment. Further studies are needed to assess these risks. 

What does this mean for sexual health services? 

Doxycycline is inexpensive and easily tolerated, so it may well become a useful STI prevention tool in the future if countries decide to approve its use.  

In June 2024, the US Centers for Disease Control and Prevention began recommending doxy PEP for transgender women and gay, bisexual and other men who have sex with men who have a history of STI infection (defined as having had syphilis, chlamydia or gonorrhoea in the past 12 months). The guidelines suggest that people who qualify should be given three to six month prescriptions alongside comprehensive STI and HIV services. They should then be reassessed before being re-prescribed with doxy PEP.  

Australia, Germany and the UK have also released doxy PEP guidelines. But these recommend more limited use due to the risk of antimicrobial resistance. 

In Kenya, two additional doxy PEP trials are now underway. One is for cisgender women ages 18-30. The other is for men who have sex with men and transgender women. Further trials are needed in a range of low- and middle-income countries and with different population groups, particularly cisgender women, adolescents and young people, to inform any potential rollout.