Post-exposure prophylaxis with doxycycline within three days of sex reduced the risk of gonorrhea, chlamydia, and syphilis.
Gay men and transgender women living with HIV or receiving pre-exposure prophylaxis (PrEP) who took the antibiotic doxycycline within 72 hours of sex had a significantly lower risk of gonorrhea, chlamydia, and syphilis, according to a study presented at the 24th International AIDS Conference in Montreal.
“Using doxycycline after having sex without condoms has the potential to be an effective strategy to substantially reduce sexually transmitted infections in target populations with high rates of STIs,” study researcher Annie Luetkemeyer, MD, of the University of California, San Francisco, told POZ.
“This isn’t for everyone,” she said at an AIDS 2022 press conference. “But there are populations that are really suffering from the STI epidemic, and it’s time to act on the data and really think about incorporating it into the guidelines and implementing this in a safe and thoughtful way.”
PrEP dramatically reduces the likelihood of contracting HIV, but foregoing condoms leaves people at risk of other sexually transmitted infections (STIs). Guidelines recommend that people using PrEP should be tested for bacterial STIs every three months, allowing for prompt treatment, but prevention would be better in the first place. Previously, the French IPERGAY trial, which evaluated on-demand PrEP, provided preliminary evidence that post-exposure prophylaxis (PEP) with doxycycline reduces the incidence of STIs .
“These are the kinds of innovations that clinicians, patients, and communities desperately need to help combat the STI epidemic in the United States,” said David Harvey, executive director of the National Coalition of STD Directors (NCSD), in a statement . “Our conclusion from the DoxyPEP study is that we are moving toward a future where symptomatic infection and community spread could be entirely unnecessary for some of our neighbors and higher-risk patients.”
The DoxyPEP trial recruited more than 500 transgender men and women who have sex with men at public health clinics in San Francisco and Seattle. Of these, 4% identified as transgender women or gender diverse. About one-third (174) were living with HIV, and 327 were taking PrEP. The median age was 38 years; 67% were white, 30% Latino, 11% Asian/Pacific Islander, and 8% Black.
The study population was at high risk for recurrent STIs. They had been diagnosed with an STI within the past year (69% with gonorrhea, 58% with chlamydia, 20% with syphilis), reported a median of nine sexual partners during the past three months, and approximately 60% reported recent substance use.
Participants were randomly assigned in a 2:1 ratio to receive either a single 200-milligram dose of oral doxycycline PEP within 72 hours of unprotected sex (not exceeding one dose in a 24-hour period) or the standard of care, which is routine testing and treatment after diagnosis. They were tested for gonorrhea, chlamydia, and syphilis every three months.
The study was scheduled to run until May 2023, but was suspended after an interim analysis showed that doxycycline PEP significantly reduces the incidence of STIs.
Among participants living with HIV, doxycycline PEP reduced the likelihood of being diagnosed with a bacterial STI per quarter by 62% compared to the standard of care (incidence of 11.8% vs. 30.5%, respectively). Regarding specific STIs, the incidence of gonorrhea decreased from 20.3% to 8.9% (a 57% reduction), chlamydia decreased from 14.8% to 3.9% (a 74% reduction), and syphilis decreased from 2.3% to 0.7% (a 77% reduction).
The risk reduction was even greater for HIV-negative participants on PrEP. In this group, there was a 66% reduction in new STIs per quarter compared to the standard care group (10.7% vs. 31.9%). Gonorrhea decreased from 20.2% to 9.1% (a 55% reduction), chlamydia decreased from 12.1% to 1.4% (an 88% reduction), and syphilis decreased from 2.7% to 0.4% (an 87% reduction).
In both groups, doxycycline-based emergency contraception was safe and well-tolerated, and adherence was high. Participants reported a median of approximately seven sexual acts per month, 87% of which were covered by doxycycline. More than half (54%) reported taking fewer than 10 doses per month, 30% took 10 to 20 doses, and 16% took more than 20 doses.
The majority of participants (88%) reported that using doxycycline after sex was acceptable, and only 1.5% discontinued it due to intolerance or personal preference. No serious adverse events or serious laboratory abnormalities were reported.
Doxycycline PEP concerns
A major concern with doxycycline PEP is that overuse of antibiotics can lead to drug resistance. Gonorrhea is already resistant to most drugs previously used to treat it. Among the subset of gonorrhea samples analyzed in this study, about 20% showed resistance to tetracycline (a related drug) at baseline, similar to the level in the US population, but this increased over time in the doxycycline PEP group.
Doxycycline is generally not used to treat gonorrhea, chlamydia, or syphilis, meaning that people who develop resistance have other treatment options. Additionally, a lower daily dose of doxycycline is used for weeks or months to prevent malaria in travelers, and this has not promoted resistance.
Another potential concern is whether frequent antibiotic use will disrupt the microbiome, the ecosystem of healthy bacteria that normally live in the gut, vagina, and other parts of the body. Antibiotic resistance and microbiome studies are ongoing.
However, Leutkemeyer noted, people in the control group acquired STIs so frequently that they still spent a substantial portion of their time in doxycycline treatment. Using doxycycline as PEP instead of treatment prevents symptoms, reduces suffering, and decreases the amount of time people can transmit STIs. In fact, some people took doxycycline so frequently—almost every day if they were sexually active—that it likely functioned as PrEP for STIs, she said.
Equitable access to doxycycline PrEP could be a problem. Some gay men are already using it before its approval for this indication, but advocates question whether it will reach everyone who needs it. A decade after its approval , Black and Latino men who have sex with men and cisgender women still do not use PrEP as much as white gay men, and the disparity is widening . Inexpensive generic versions of doxycycline are widely available, but the cost could increase if people take it frequently.
Cisgender women and transgender men may also benefit from doxycycline PEP, but it has not yet been studied in these groups. DoxyPEP researcher Connie Celum, MD, MPH, of the University of Washington, said a study of cisgender women is underway in Kenya and should have results next year.
The NCSD is working to update STI programs based on the DoxyPEP results and plans to advise the Centers for Disease Control and Prevention (CDC) on the on-the-ground implications.
“We urge the CDC to immediately put this research in the hands of physicians and update treatment guidelines so that patients do not have to wait for best-in-class care,” Harvey said.
In a statement responding to the study results , the CDC said they are "encouraged" by the initial data.
“Further review of the submitted data and potentially additional analysis will be needed to develop clinical guidance on the safe and effective use of this strategy for the prevention of bacterial STIs among gay and bisexual men and transgender women. It will be critical to provide guidance that maximizes effectiveness for STI prevention while minimizing risks to public and individual health,” the agency stated. “We must act quickly to implement powerful STI prevention strategies. And it is our public health imperative to develop responsible guidance based on careful consideration of all available data and the risks and benefits to public health; we cannot cut corners when it comes to people’s health.”
Doxycycline PEP adds a new tool to the safer sex toolkit, but, as happened with HIV prevention pills, some worry that it may encourage people to have more sex without a condom.
“When PrEP first came out, we saw a lot of shame and stigma—why not just use a condom?—but we need multiple tools. I hope this doesn’t come with the shame and guilt that came with the first round of PrEP,” Leutkemeyer said.
"The [DoxyPEP] data corroborates the harm reduction practices that many of us in PrEP have already adopted," Damon Jacobs told POZ. “We have the right and the ability to enjoy sexual pleasure and minimize risk at the same time.”