It is not very often that we are able to report on a new breakthrough in sexually transmitted infection/disease treatment or prevention. The first ones were #PEP and #PrEP to halt HIV infection either AFTER exposure or BEFORE condomless anal sex, respectively. They were followed by #U=U regarding the fact that those living with HIV, on effective treatment, cannot pass the virus on to their sexual partners. Now, DoxyPEP has joined their ranks.

With the more widespread use of PrEP, concerns arose about the rise in other sexually transmitted diseases such as gonorrhea and syphilis. Everyone from LGBTQ orgs to governments and the average gay man wondered if this new preventative medication was fueling the rise in other STDs. And if so, what is the solution?

Research has proven that, mainly due to testing, STD rates see a rise BEFORE PrEP usage, NOT AFTER.

Over the last few decades, before PrEP, there were reports around the globe of higher rates of infection for STDs among not only homosexual males but all sexually active population groups.

The concerns you may have regarding using PrEP in the face of other STDs are valid, as this medication does not protect you from them. But there is another medication proven to be effective in this regard. But it also comes with pros and cons in usage.

We are pleased to share with you information from a study regarding the medication doxycycline and its ability to prevent STDs & infections AFTER exposure (PEP) and BEFORE (PrEP).

All medications carry some level of risk and potential side effects. Still, DOXYPEP has given rise to concerns about its effectiveness in preventing bacterial STDs as well as possible issues of medication resistance.

We break down the research, facts, and concerns to help you decide if DOXYPEP is right for you!

What is Doxycycline?

Doxycycline is a broad-spectrum tetracycline-class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis.

It is also used to prevent malaria in combination with quinine. Doxycycline may be taken by mouth or by injection into a vein.

Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production.

Common side effects include:

Doxycycline was patented in 1957 and came into commercial use in 1967. It is on the World Health Organization’s List of Essential Medicines. Doxycycline is available as a generic medicine. In 2019, it was the 90th most commonly prescribed medication in the United States, with more than 8 million prescriptions.

What were the research findings?

A US study that provided gay and bisexual men with the antibiotic doxycycline to take after condomless sex was stopped a year early because of its high efficacy, the 24th International AIDS Conference in Montreal was told on the 28th of July, 2022. 

The DoxyPEP study compared the incidence of gonorrhea, chlamydia, and syphilis in 374 people who were given doxycycline to take after sex with the incidence in 180 people who were not provided with the drug. It found that doxycycline cut the risk of STIs by two-thirds.

The study involved 360 HIV-negative people using HIV pre-exposure prophylaxis (PrEP) and 194 HIV-positive people, aged over 17 and born male, attending two clinic sites in Seattle and San Francisco. The other criterion for the study was that they had to have had at least one of the three STIs in the last year.

An interim review of 13 May 2022 found that efficacy was so high it would be unethical to continue with the control arm, and all participants were given doxycycline.

Important findings from the study are:

  • Efficacy in the HIV-negative participants was 66%
  • Efficacy against chlamydia was high, at 79% in HIV-negative people
  • Efficacy was still significant against gonorrhea, at 59% in people without HIV
  • Syphilis efficacy was 76% in HIV-negative people
  • Efficacy in the participants with HIV was a bit lower, at 62%, but still significant.
  • Efficacy against chlamydia was 70% in people with HIV
  • Efficacy against gonorrhea was still significant, against gonorrhea was 57% in people with HIV
  • Syphilis efficacy was 42% in people with HIV, but the number of infections was small (three versus two in the DoxyPEP and control arms in HIV-positive people), so this lower efficacy in people with HIV may not be significant
  • Adherence to doxycycline was good, with 87% of incidents of condomless sex protected by it
  • More than half of the participants (54%) took fewer than ten PEP doses a month, 39% took 10-20 doses, and 16% took over 20 doses (so almost daily).
  • There were no serious adverse events

“Until now, it has not been certain whether doxycycline would work as post-exposure prophylaxis (taking it after sex – ­­­­PEP). A couple of previous studies have been done, a small one in the US in 2015, and a French study in 2017. But both of these used daily STI pre-exposure prophylaxis (taking it before sex – PrEP).  Furthermore, while both studies cut the incidence of syphilis, the US study had no significant effect on chlamydia, and neither had an effect on gonorrhea. In the latter case, this was ascribed to the fact that there are many strains of gonorrhea resistant to doxycycline.”

The efficacy of DoxyPEP now opens up the possibility of its more widespread use as STI prophylaxis. DoxyPEP implies taking the drug less often than for DoxyPrEP, both saving money and reducing concerns about the overuse of antibiotics leading to resistance and side effects. 

Safer Sex Practices

As important as this study is, so is maintaining a full and complete toolkit for safer sex healthcare. This may range anywhere from serosorting your sexual partners, understanding and believing in the science behind #uequalsU, taking precautions against HIV infection with #PrEP and #PEP, as well as using condoms.

Doxycycline is just one more component that is available. It should not be a total supplement to your entire current sexual healthcare regime.

  • natural/condomless sex has been on the rise within the gay male community for some time and this trend does not seem to be slowing down. With this in mind, being honest about your sexual choices with yourself, your partners, and your doctor is important.
  • honesty with a doctor can only happen if you choose the right one for you and your comfort level. Your provider can not assist you in maintaining proper sexual healthcare standards if they do not have a complete picture of your sexual life. They are also less likely to prescribe medications like PrEP for you or schedule regular STI check-ups.
  • knowing your full STI status, not just for HIV is vital information for you and your sexual partners. This information will help you make the most informed decisions about which safer sex practices are best for you and how successful they may be.

Possible CONS to using DoxyPrEP

To be clear, this medication is safe and effective to use. The issues raised around its usage concerns:

  • How effective is it in preventing gonorrhoea?

The Australian Society for HIV Medicine (ASHM) released a Consensus Statement in March 2024, which, in fact, had to record that it failed to reach complete consensus on its proposed guidelines for doxyPEP use. The statement summarised a meeting on 17 March 2024, in which there was general agreement that doxyPEP should be considered “primarily” for the prevention of syphilis in gay and bisexual men who are at risk of it – but added that “for some individuals the reduction in chlamydia and lesser reduction in gonorrhoea might be important.”

On 30 November 2024, the Belgian Research HIV Consortium (BREACH) released a short statement saying they had reached a consensus “not to recommend the widespread use of doxyPEP for the prevention of STIs.”

They had two concerns. Firstly, they said that in the studies, although doxyPEP proved effective for syphilis and chlamydia, and in some cases gonorrhoea, “the number of symptomatic infections was low or not reported”. They pointed out that screening initiatives aimed at identifying and treating asymptomatic STIs, such as the Belgian Gonoscreen programme, did not result in falls in gonorrhoea incidence, so why should doxyPEP?

The news was less good from France, where a re-analysis of the data from the DOXYVAC study found that, although the efficacy against chlamydia and syphilis was confirmed mainly (at 86% and 79% respectively), doxyPEP’s efficacy against gonorrhoea fell to only 33% (still statistically significant but not very useful), while the efficacy of the vaccine was only 22% and was not statistically significant.

The concerns regarding doxyPEP’s ability to prevent infection from gonorrhea stem from the fact that the gonorrhoea organism is already largely resistant to doxycycline, the very reason it stopped being used as a treatment in the late 1980s.

Resistance, in fact, varies substantially from place to place. The proportion of gonorrhoea resistant to antibiotics of the tetracycline class ranges, according to one survey of European countries, from 14% in Estonia to 94% in Portugal (and 92% in France). It is also highly local and dependent on previous prescribing practices – in Spain, next door to Portugal, it is only 18%.

This creates doubts about how doxyPEP should be prescribed in relation to preventing gonorrhoe.

  • The possibility of individuals developing medication resistance for treating gonorrhoea

Because DoxyPEP uses the same medication used to treat gonorrhea infection, a widespread prevention tool that does not provide major results, can alter one’s body to develop resistance to the medication when needed to cure it.

This is no longer a potentiality but a fact. As doxyPEP use has risen, these concerns about resistance have been confirmed. A report in The New England Journal of Medicine showed that extensively drug-resistant gonorrhoea is spreading.

The increase coincided with a shift away from azithromycin toward doxycycline for chlamydia treatment and also growing use of doxyPEP. “These results suggest that widespread use of doxycycline for the treatment and prevention of sexually transmitted infections may be contributing to reshaping of the gonococcal population in the United States,” the researchers wrote.

The prevalence of drug resistance varied by region in the US, being highest in the northwest, which includes Seattle, an early adopter of doxyPEP. A previous report from the city found that high-level tetracycline resistance among gay men with gonorrhoea rose from 2% in early 2021 to 65% by the end of 2024.

Specifically, taking more than three doses of doxyPEP per month was associated with having both overall and high-level resistance. In addition, tetracycline-resistant Staphylococcus aureus and group A Streptococcus were more common among doxyPEP users compared with non-users.

Gonorrhoea resistance rates are even higher in other parts of the world. A recent systematic review and meta-analysis published in JAC-Antimicrobial Resistance, which included studies conducted before the advent of doxyPEP, found that the prevalence of tetracycline-resistant N. gonorrhoeae ranged from 27% in North America to approximately 50% in Europe, and more than 80% in sub-Saharan Africa and East Asia.

Should you take DoxyPEP/PrEP?

This is a question that only you can make for yourself, with input and advice from your medical provider(s). Homosexual males are at greater risk for all sexually transmitted illnesses, not just HIV, for varying reasons. Only you know what your actual sexual life is and how high your risk level is.

Taking in all of the above information, those living with HIV or most at risk for contracting this illness have been advised by medical institutions around the world to use doxyPEP, but with caution. The risk of developing resistance is not zero, and it does depend on how often you use this treatment and where you live in the world.

Before you go…

Just like the majority of you, we have had our own experiences with contracting an STI, and we hate it each time it happens. Instead of slut shaming, we believe education and freedom to tell the truth to our doctors and sexual partners is the best way to reduce the incidence of infections within our community. Shame helps no one.

Aside from reductions in syphilis and chlamydia, doxyPEP can decrease anxiety around sex, and this can result in a broader sense of sexual empowerment. The absence of STIs should not solely define good sexual health. It should also encompass the reduction of related shame, anxiety, and stigma, as well as the enhancement of pleasure as core to sexual health.

If the monkeypox outbreak should teach us anything, it should be that contracting an STI is much more complex than just the exchange of bodily fluids. And, along with bacterial infections, some viruses can easily be spread through intimate touch. Keep this in mind, the next time you or someone you know attempts to use coercion and shaming to stop the spread of STIs, because it does not work.

Only compassion, understanding, education, and communication have succeeded. Along with practicing some form of safer sex/sexual healthcare is also essential.

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