DoxyPEP: Using antibiotics to prevent STIs

Maybe you’ve heard about doxyPEP and you’re considering using antibiotics to prevent sexually transmitted infections (STIs). Or maybe this is already part of your sexual health routine. If either is the case, this factsheet is for you, as there are some important points to consider.

It is important to keep in mind that some medical guidelines don’t yet recommend using antibiotics in this way. There remains a concern about whether it may lead to the spread of bacteria that are resistant to doxycycline, which is an antibiotic needed to treat a wide range of infections. There is no evidence to suggest that using any other antibiotics than doxycycline would prevent STIs.

This factsheet presents some of the research that has been done, real-world data, and the potential pros and cons of using this approach. So far, most of the research has been done with gay and bisexual men; one study with cisgender women in Kenya had disappointing results.

What is STI prophylaxis?

STI prophylaxis involves taking an antibiotic pill to prevent bacterial STIs, such as syphilis and chlamydia.

So far, the research has focused on taking a single dose soon after sex. This is considered post-exposure prophylaxis (STI PEP) – the antibiotic seems to prevent bacterial growth and makes it less likely for exposure to lead to infection. This approach has proven effective for gay and bisexual men and transgender women.

Another approach would be to take a daily dose of the antibiotic – this would be considered pre-exposure prophylaxis (STI PrEP), meaning that there may be enough of the antibiotic in the body before exposure occurs.

This factsheet focuses specifically on using antibiotics to prevent bacterial STIs. It is not to be confused with HIV PrEP and PEP, which are effective forms of preventing HIV, as outlined below.

	Medication	Does it prevent HIV?	Does it prevent bacterial STIs?
STI pre-exposure prophylaxis (STI PrEP or doxyPrEP)	Doxycycline (antibiotic)	No	Research ongoing, but may work against chlamydia, syphilis and gonorrhoea.
STI post-exposure prophylaxis (STI PEP or doxyPEP)	Doxycycline (antibiotic)	No	Effective for gay and bisexual men and trans women in three studies; research in other populations is ongoing. Works against chlamydia and syphilis and to a lesser extent, gonorrhoea.
HIV pre-exposure prophylaxis (HIV PrEP)	Tenofovir / emtricitabine (two antiretrovirals)	Yes	No
HIV post-exposure prophylaxis (HIV PEP)	Raltegravir / tenofovir / emtricitabine (three antiretrovirals)	Yes	No

Does doxyPEP work?

Three key randomised controlled trials have shown the efficacy of using doxycycline preventatively, when taken as post-exposure prophylaxis. There is also good emerging evidence for doxyPEP use from clinical settings, and data from San Francisco showing its potential to reduce syphilis and chlamydia burden at the population level.

Doxycycline prevents bacteria from reproducing and effectively treats various bacterial infections, including pneumonia, gum disease, skin infections and some STIs. Doxycycline is also used to prevent malaria infection.

Research has largely been carried out with gay men who have multiple sexual partners and don’t use condoms, as they represent the group at highest risk for recurrent bacterial STIs. In each study, some participants were instructed to take a 200mg doxycycline dose (two 100mg pills) within 24 hours after sex (and no later than 72 hours after) – this is doxycycline post-exposure prophylaxis, or doxyPEP.

A French trial recruited 232 gay and bisexual men who were already taking PrEP for HIV, and at a high risk for contracting bacterial STIs. They were randomised to two groups: those in the experimental group were given doxycycline to take after sex and men in the other group did not take any antibiotics.

Over a follow-up period of around nine months, there were 47% fewer infections with one of the three main bacterial STIs (syphilis, chlamydia and gonorrhoea) in the men taking doxycycline. While the antibiotic had no effect on gonorrhoea, with similar numbers of infections between both groups, there were 70% fewer chlamydia infections and 73% fewer syphilis infections in the men taking doxycycline when compared to those not taking it.

The gonorrhoea finding was perhaps not surprising: around half of the French and two-thirds of the UK strains of gonorrhoea, and around a quarter of those in the US, are resistant to tetracycline antibiotics (doxycycline belongs to this class). However, these antibiotics are not usually used in the treatment of gonorrhoea because of the high rates of resistance (see section on What about resistance?).

A second large study – the US DoxyPEP study – reported results in July 2022. A total of 501 gay and bisexual men and trans women who were either living with HIV (174) or taking HIV PrEP (327) were randomised to either take doxyPEP or to not receive any antibiotics. As with the French study, the participants were at a higher risk of contracting bacterial STIs, with just under half of the group reporting either gonorrhoea, chlamydia or syphilis in the past year. Participants were tested for STIs every three months.

Overall, there was a 66% reduction in the incidence of all STIs per quarter in both those living with HIV and those taking HIV PrEP. In fact, the study was stopped a year early because of the high efficacy, with a recommendation for participants in the control groups to receive doxyPEP too.

In terms of specific STIs, doxycycline worked well to prevent chlamydia, syphilis and gonorrhoea, unlike in the French study. For people living with HIV, there was a 74% reduction in chlamydia, 77% reduction in syphilis (not statistically significant, possibly due to the low number of syphilis infections) and 57% reduction in gonorrhoea. For people taking HIV PrEP, there was an 88% reduction in chlamydia, 87% reduction in syphilis and 55% reduction in gonorrhoea.

One of the possible reasons for the gonorrhoea finding is that tetracycline resistance in gonorrhoea is not as widespread in the US as it is in France or the UK. An analysis of gonorrhoea resistance among participants in this study showed only modest increases in the proportion of gonorrhoea infections with significant resistance, with little difference between those taking doxyPEP and those not taking it.

A third large study – the Doxyvac study – by the same French research group as the trial mentioned above, presented interim results in February 2023. From a sample of 502 gay and bisexual men on HIV PrEP, 332 were randomised to take doxyPEP (200 mg within 72 hours after sex as in prior studies), while the rest did not take doxycycline. As with the previous trial, these men had high rates of bacterial STIs diagnosed in the past year – 68% had had gonorrhoea, 50% chlamydia and 20% syphilis. Participants were tested for STIs at baseline, and every three months, or if they presented with symptoms, for a median period of nine months of follow-up.

DoxyPEP was found to be highly efficacious after a year of follow-up, reducing the incidence rate or the first documented episode of chlamydia and syphilis by 89% and 79%, respectively. An unexpected interim finding was that the incidence rate of gonorrhoea also decreased by 51%. However, this was later corrected: in a final analysis of 545 participants with 21 months of follow-up, the reductions for chlamydia and syphilis were similar to the interim results, at 86% and 79% respectively, but there was only a 33% reduction in the incidence of gonorrhoea.

This study also investigated the efficacy of a vaccine (the same one used to prevent meningitis B) against gonorrhoea. It did not significantly reduce new cases of gonorrhoea among the men assigned to take it, and likely offers little clinical benefit. 

The only study done with cisgender women – the dPEP Kenya trial – found that doxyPEP did not prevent bacterial STIs among 449 women taking HIV PrEP. Between 2020 and 2022, non-pregnant cisgender women with a median age of 24 were randomised to either take doxycycline after sex, or to receive standard of care management (quarterly STI testing and treatment after diagnosis). All women were tested for STIs quarterly.

STI rates were high during the study, with an annual incidence of 27%. However, doxyPEP did not reduce the number of STIs, with no statistically significant differences detected between the treatment and standard of care groups for chlamydia or gonorrhoea. There was only one case of syphilis. DoxyPEP’s lack of efficacy in this instance appears to have come down to poor adherence: an objective measure (doxycycline in randomly selected hair samples from 50 women) showed that as many as 44% of women in the doxyPEP arm may not have taken the drug at all. This is in contrast to reported adherence, which was much higher.

All the studies mentioned so far involved taking a single dose of the antibiotic after sex (doxyPEP). There has only been one study on daily doxycycline use (doxyPrEP). A small US pilot study randomised 30 gay men living with HIV, who had had syphilis twice or more since their HIV diagnosis, to one of two groups. Men who took 100mg of doxycycline by mouth daily were 73% less likely to test positive for gonorrhoea, chlamydia or syphilis during 48 weeks of follow-up, compared to men who had been provided with monetary incentives to remain STI free. There was no significant difference in reported risk behaviours between the two groups. A study into the use of doxyPrEP by gay and bisexual men in Australia is underway, with results expected in 2025. Canadian researchers are conducting a study comparing doxyPrEP and doxyPEP among gay and bisexual men, expected to finish in 2027. 

Further research on both doxyPEP and doxyPrEP is needed with cisgender heterosexual women and men.

Real-world experience

Based on the research findings, San Francisco was the first city to recommend doxyPEP in 2022. In addition to recommending it to gay and bisexual men and trans women at a higher risk of contracting STIs, their guidelines also offer shared decision-making for trans men, and those with multiple sexual partners who have not had a recent STI. This approach allows for discussion with a healthcare provider regarding whether doxyPEP could be a beneficial option, despite a lack of evidence.

Results from San Francisco AIDS Foundation’s Magnet sexual health clinic, where doxyPEP was offered to 3,000 HIV PrEP users in November 2022, showed high demand, with 39% of all PrEP users opting to take doxyPEP by September 2023. Among this group, overall STI incidence fell by 58% during this period – a drop not seen in those who chose not to take doxyPEP. As seen in the clinical trials, the reductions were most marked for chlamydia and syphilis: 67% and 78%, respectively. There was an 11% reduction in new cases of gonorrhoea, but this was not statistically significant.

Another San Francisco site, City Clinic, saw even higher uptake of doxyPEP among 506 HIV PrEP users, at 73%. While positive chlamydia tests declined by 90% when comparing the pre-doxyPEP period to after the roll-out, the reduction in new syphilis cases was not statistically significant, with a small number of overall cases. Once again, doxyPEP did not reduce the number of new gonorrhoea cases.

With three sexual health clinics in San Francisco offering doxyPEP by late 2023, population level trends could be investigated. A marked effect was noted among those offered doxyPEP: gay and bisexual men and trans women. With more than 3,500 doxyPEP users from these populations in the city, chlamydia cases decreased by half, compared to predicted levels using 2021-2022 data; syphilis cases deceased by 51% after 13 months of doxyPEP availability. There was no significant change in gonorrhoea cases at the population level.

New chlamydia cases among cisgender women – a group not offered doxyPEP – increased when compared to the earlier period, strengthening the finding that the drop seem among gay men and trans women was due to doxyPEP uptake.

Why some guidelines don’t recommend this

In June 2024, the US Centers for Disease Control and Prevention issued guidelines recommending doxyPEP use for gay and bisexual men and trans women who have had a bacterial STI in the past year, with STI testing at baseline and every 3-6 months thereafter. The ongoing need for doxyPEP should also be reassessed every 3-6 months.

Local guidelines in some parts of the US also already support doxyPEP. Forthcoming guidance from both the European AIDS Clinical Society and the International Antiviral Society–USA (IAS–USA) are expected to be supportive too.

However, some other public health agencies have been less enthusiastic about recommending doxyPEP – mainly due to concerns regarding the development of antimicrobial resistance.

The Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) have issued a consensus statement on doxyPEP, outlining the evidence in favour of doxyPEP’s effectiveness – primarily for preventing syphilis among gay and bisexual men. However, ASHM urges clinicians to consider adverse outcomes associated with long-term use, such as resistance and changes to the gut microbiome. The German STI Society only recommends doxyPEP on a case-by-case basis, as an off-label use of the antibiotic. The Belgian Research HIV Consortium is even more cautious: they have stated that they do not recommend the widespread use of doxyPEP to prevent STIs, and only recommend that it be used in research contexts.

A central question for guidelines is the balance of harm vs. benefit. Among cisgender men, STIs such as chlamydia and gonorrhoea are often asymptomatic. They sometimes clear spontaneously, but in other cases will later become symptomatic if left untreated. These STIs also pose less danger for cisgender men than they do for cisgender women, whose fertility can be severely damaged by complications of untreated STIs. Thus, the benefits offered by doxyPEP for people assigned male at birth, especially in the case of chlamydia, may not outweigh risks associated with the development of antimicrobial resistance.

However, it’s important to note that even asymptomatic bacterial STIs may be passed on to sexual partners and they may increase the chances of contracting HIV for those who are HIV-negative.

A much clearer benefit of doxyPEP applies to the prevention of syphilis as this bacterial STI can have serious consequences in all populations, such as ocular syphilis and neurosyphilis, and signs of an initial infection may easily be missed, allowing the disease to progress to the next stage. Syphilis will not go away if left untreated, even though there may be long periods with no symptoms.

In most instances, healthcare professionals treat STIs based either on symptoms, the results of laboratory tests, or both. Sexual health clinicians have less experience of prescribing antibiotics to be taken prophylactically (to prevent STIs before any symptoms or testing positive). In this context, there are concerns about the development of antimicrobial resistance. Taking a drug and then (despite prophylaxis) catching an infection that easily develops resistance to it could further raise rates of resistance to that drug in the wider community. Resistance means that medications that were once effective at treating certain bacterial infections lose their ability to do so. Essentially, the bacterium outsmarts the medication, rendering it ineffective.

Resistant strains circulate within the population, resulting in the failure of treatments that had previously worked – even in people not using antibiotics to prevent STIs. Gonorrhoea has evaded multiple classes of antibiotics, and few options remain available. Most recently, it has become resistant to azithromycin and therefore, this antibiotic is no longer recommended for treatment.

There is a danger of running out of antibiotics that work to treat a resistant strain; this complicates treatment and could negatively impact upon health outcomes. Resistance is a concern both for bacteria that cause STIs and other common infections.

However, when it comes to using specific antibiotics to prevent specific STIs, it’s not all bad news – see more under What about resistance?

Who could benefit from doxyPEP?

The available evidence for doxyPEP only applies to gay and bisexual men and transgender women.

In instances where doxyPEP is recommended, it applies to people who have had a bacterial STI in the past year. Shared decision making, or discussion with your healthcare provider, is recommended if you have not had a recent STI, but have behaviours that might put you at risk for one, such as condomless sex, multiple sexual partners, or a combination of factors.

If you do not use condoms consistently, or at all, have multiple sexual partners and have had bacterial STIs in the past year, doxyPEP could benefit you.

The evidence shows that doxyPEP is effective against syphilis and chlamydia, but tends to be less effective in preventing gonorrhoea. This appears to vary from place to place, probably because resistant strains of gonorrhoea are much more common in some places than others. 

DoxyPEP can be taken regardless of HIV status. Many individuals who are HIV negative and on HIV PrEP use condoms less frequently or have stopped using them altogether. Similarly, some who are living with HIV also choose not to use condoms all of the time as an undetectable viral load prevents HIV transmission.

An accepted public health approach promotes the control of STIs among those at highest risk as a way of reducing STIs in the general population. An Australian modelling study supports this notion: it estimated that if half of Australian gay men took doxycycline as PrEP, and it was 70% effective against syphilis, then rates of syphilis would decrease by 50% after a year and 85% after a decade. Interestingly, the same finding applied if only 50% of the highest-risk group (men with more than 20 partners in six months) were taking doxycycline. This indicates that targeted interventions could have widespread community-level benefits.

Surveys in Australia, Germany, the US and the UK show high levels of interest among gay men and some healthcare providers in using doxycycline to prevent STIs, with some men already using this approach – often by obtaining doxycycline through informal channels. However one UK survey showed that among those who said they had used STI prophylaxis, only 56% had used doxycycline, others had used antibiotics such as amoxicillin (20%) and azithromycin (18%). There is no evidence to suggest that antibiotics other than doxycycline would be at all effective in preventing STIs.

For some groups, such as sex workers, negotiating condom use can be challenging and biomedical forms of prevention, such as HIV PrEP, have been a crucial form of protection. STI prophylaxis could be another valuable protective tool in this instance.

When should doxyPEP be taken?

Guidelines recommend a 200mg dose after a sexual encounter (ideally within 24 hours and no later than 72 hours). No more than one dose should be taken every 24 hours. As STIs are not only passed on through penetrative sex, you should also take doxyPEP in cases where only oral or other sex acts took place.

If you’ve had multiple sexual partners over a weekend, one 200mg dose on Monday morning would suffice.  As doxycycline usually comes in 100mg pills, a helpful way to remember is the 3:2:1 rule: within 3 days of sex, 2 pills, no more than 1 dose per day.

What about resistance?

STIs are caused by different strains of bacteria and are treated with antibiotics that are known to be effective against the specific bacterium that causes the infection. In some cases, an antibiotic that previously worked stops working, because the bacterium has developed resistance to it.

Doxycycline has been used prophylactically and as long-term treatment in various instances. However, there is always concern that resistance to a drug could develop as a result of increased use.

Gonorrhoea: some strains are resistant to doxycycline, so the drug may vary in its effectiveness at preventing gonorrhoea depending on the context, as was documented in the French and Kenyan studies. Importantly, doxycycline is not used to treat gonorrhoea. This means that use of doxycycline as prophylaxis should not complicate the treatment of a gonorrhoea infection, should one occur.

Syphilis: there is currently no evidence of doxycycline resistance in syphilis, although there is always the concern that it could develop as doxycycline is the first choice for treating syphilis in people who are allergic to penicillin. Recently, syphilis developed high level resistance to the antibiotic azithromycin within a few years of it being used as syphilis treatment.

Chlamydia: doxycycline is the first-line treatment for uncomplicated chlamydia in the UK and other countries. This means that the development of doxycycline resistance would be a serious concern with very few available treatment options remaining. There have been some cases of doxycycline treatment failure, but the studies did not test for resistance and the causes of treatment failure are unclear. Encouragingly, many studies in communities with frequent use doxycycline use have not found evidence for resistance in chlamydia.

Mycoplasma genitalium (MG): there is concern about resistance to this STI which is a frequent cause of urethritis (an inflammation of the urethra – the tube that carries urine out of the body) in men. Doxycycline is a recommended alternative medication to treat uncomplicated MG because of emerging resistance to first-line treatments, such as azithromycin. More widespread use of doxycycline among those with high prevalence of MG, such as gay men, could become an issue in future and requires further research.

Other infections: doxycycline is an important treatment for community-acquired pneumonia and other infections. Continued exposure to doxycycline is therefore a concern in terms of causing resistance in other organisms that are not sexually transmitted. This would limit treatment options for the individual and others in the future.

For instance, among people taking doxycycline in the US DoxyPEP study mentioned above, there was a significant 8% increase in the number of samples of Staphylococcus aureus (a bacterium that is usually present in the nose and throat) that were resistant to doxycycline. However, researchers stated that overall, the numbers of new doxycycline-resistant bacteria that emerged were small and that population-level monitoring will be important once doxyPEP becomes more widely used.

What about side effects?

Doxycycline is generally safe and well-tolerated. This is true even when it is used for long periods of time, as is the case when it is used to treat acne and as malarial prophylaxis. The most common side effects are gastrointestinal, such as diarrhoea, vomiting and nausea. Increased sensitivity to light can also be a concern with prolonged use. In most instances, side effects resolve once doxycycline is discontinued.

Doxycycline should not be used by pregnant people, or those who might become pregnant.

There is also concern regarding how ongoing antibiotic use affects the gut microbiome, including the impact on good bacteria and overall health. In the first French study mentioned above, only eight of 232 men discontinued doxycycline due to gastrointestinal side effects. In the US DoxyPEP study, there were no serious adverse events reported and only 1.5% of the study group discontinued due to intolerance or participant preference. In fact, 88% reported that doxyPEP was either acceptable or very acceptable. Similarly, there were no serious adverse events related to doxycycline during the Doxyvac study, with only three participants discontinuing treatment due to side effects such as nausea, abdominal pain and diarrhoea.

The two most common formulations are monohydrate and hyclate, with monohydrate (or coated hyclate) generally better tolerated.

Gastrointestinal side effects can be minimised by taking doxycycline with food, and staying upright for at least 30 minutes after taking it to prevent reflux.

Summing up

Three rigorous studies have shown that doxyPEP (taking doxycycline soon after sex) prevents STIs when used by gay and bisexual men, and one of the studies showed it worked for trans women too. Based on one study so far, doxyPEP did not prevent STIs among cisgender women. More research is needed with this group.

There is also emerging evidence of the effectiveness of this approach outside research settings. While some public health agencies have been enthusiastic about having a prevention tool for bacterial STIs, others have been more cautious in their recommendations.

Potential bacterial resistance needs to be monitored at a population level with increased regular use of doxycycline. Concern about resistance should be balanced by the potential benefits doxyPEP has to offer, especially for gay men and trans women with recurrent STIs.