US releases first doxyPEP guidelines for preventing sexually transmitted infections

Africa Studio/

On October 2, the US Centers for Disease Control and Prevention (CDC) issued proposed guidelines for using the antibiotic doxycycline as post-exposure prophylaxis to prevent bacterial sexually transmitted infections (STIs), an approach known as doxyPEP.

The guidelines are the first national effort to define how to use the new prevention tool, and they likely will influence doxyPEP implementation in other countries as well.

"Until effective and affordable vaccines are developed, doxyPEP provides one short-term tool to address the ongoing increases in some bacterial STIs, especially syphilis, in key groups of people,” Dr Will Nutland, co-director of PrEPster at The Love Tank, told aidsmap. “The US draft guidance brings us one step closer to broader availability of doxyPEP.”

The proposed guidelines state that a single 200mg dose of oral doxycycline taken within 72 hours after oral, anal or vaginal sex should be considered for gay, bisexual and other men who have sex with men and for transgender women who have had gonorrhoea, chlamydia or syphilis at least once during the past year. This is a strong recommendation supported by data from clinical trials.

The draft also says that doxyPEP “could be considered” for men who have sex with men and transgender women who have not been diagnosed with an STI if they “will be participating in sexual activities that are known to increase likelihood of exposure to STIs, e.g., during weekend events, cruises and festivals,” although this has not been directly assessed in trials.

However, due to a lack of supporting evidence, the guidelines state that “no recommendation can be given at this time” on the use of doxyPEP for cisgender women, cisgender heterosexual men, transgender men or other queer or non-binary people.

“DoxyPEP will be of most use in groups with the highest incidence of bacterial STIs, particularly highly sexually active gay and bisexual men,” Nutland said. “Yet we must continue to emphasise the lack of evidence to support its use in some population groups.”

According to the guidelines, doxyPEP “should be implemented in the context of a comprehensive sexual health approach including risk reduction counselling, STI screening and treatment, recommended vaccination and linkage to HIV pre-exposure prophylaxis (PrEP), HIV care or other services, as appropriate.”

DoxyPEP research

The draft guidelines are supported by results from the DoxyPEP trial, which enrolled more than 500 men and transgender women who have sex with men at public health clinics in San Francisco and Seattle. About a third were living with HIV and the rest were taking PrEP. They were randomly assigned to take a single dose of oral doxycycline within 72 hours after condomless sex or the standard of care, which is regular testing and treatment following an STI diagnosis.

As reported at the 2022 International AIDS Conference, doxycycline reduced the risk of acquiring chlamydia by 74% and syphilis by 77% for people with HIV. For those taking PrEP, the risk reduction was 88% for chlamydia and 87% for syphilis. DoxyPEP was less effective at preventing gonorrhoea, with a risk reduction of 57% for people with HIV and 55% for HIV-negative people. The French DoxyVAC trial also showed that doxycycline reduced the risk of acquiring these STIs.

However, a study of cisgender women in Kenya found taking doxycycline after sex did not significantly reduce the risk of STIs in this population. Although the drug appeared to reach adequate concentrations in vaginal and cervical tissues, many participants reported suboptimal adherence, suggesting doxyPEP still might have the potential to protect women if used more consistently.

Accordingly, the CDC guidelines recommend doxyPEP for cisgender men who have sex with men and transgender women with a history of STIs, the group with the strongest evidence of benefit, but “they leave the door open for other populations,” according to DoxyPEP lead investigator Professor Annie Luetkemeyer of the University of California San Francisco.

“We don't have data for men who have sex with women, and we don’t have data to support its use in cisgender women yet. However, clinicians can use the guidance to have a case-by-case discussion with people who aren’t included in the recommendation to decide if doxyPEP makes sense while we are learning more,” she said. “The CDC could have stated that doxyPEP should not be given to anyone outside of the recommendation, but that would be overly narrow.”

DoxyPEP concerns

Although doxycycline is generally safe and well tolerated, preventive use is not without concerns. One is that widespread use of antibiotics could lead to drug resistance. This is especially worrisome with regards to gonorrhoea, which is already resistant to many medications.

Leutkemeyer presented an analysis of resistance data from the DoxyPEP trial at this year’s Conference on Retroviruses and Opportunistic Infections. “We didn’t see a marked increase in antimicrobial resistance associated with doxyPEP use,” she said at a press briefing. “We need larger and longer studies of what happens to common bugs,” but this must be weighed against the benefits of a substantial reduction in STIs. In fact, using doxyPEP to prevent STIs—rather than treating them after they occur—could potentially reduce overall prevalence, giving bacteria less opportunity to circulate and develop resistance.


cisgender (cis)

A person whose gender identity and expression matches the biological sex they were assigned when they were born. A cisgender person is not transgender.


An umbrella term for people whose gender identity and/or gender expression differs from the sex they were assigned at birth.


A sexually transmitted infection caused by the bacterium Treponema pallidum. Transmission can occur by direct contact with a syphilis sore during vaginal, anal, or oral sex. Sores may be found around the penis, vagina, or anus, or in the rectum, on the lips, or in the mouth, but syphilis is often asymptomatic. It can spread from an infected mother to her unborn baby.


Refers to the mouth, for example a medicine taken by mouth.


Antibiotics, also known as antibacterials, are medications that destroy or slow down the growth of bacteria. They are used to treat diseases caused by bacteria.

Another concern is that frequent antibiotic use could disrupt the microbiome, the ecosystem of healthy bacteria that normally live in the gut and elsewhere in the body. The CDC guidelines state that these risks will need to be closely monitored.

Equitable access will also be an issue in the implementation of doxyPEP. Inexpensive generic doxycycline is widely available, but cost could add up if people use it frequently. What’s more, everyone who could potentially benefit from this new prevention tool may not have access to sex-positive healthcare providers who know about the intervention and will offer it without stigma. And further research is needed on the use of doxyPEP by cisgender women and other populations.

“It is clear that in the face of rising STI rates, our current tools are not sufficiently effective, so I welcome the introduction of a new tool that is,” Dr Laura Waters of the Mortimer Market Centre in London told aidsmap. “However, careful monitoring of resistance is important, as is understanding the lack of efficacy in women. We must be cautious in rolling this intervention out to populations where evidence does not show benefit or, in the case of men who have sex with women, is lacking entirely.”