In June, the drugmaker Pfizer announced that its long-acting injectable antibiotic Bicillin (penicillin G benzathine), the first-line treatment for the sexually transmitted infection (STI) syphilis, was undergoing a supply shortage that likely would not be fully resolved for a year. One of the reasons for the shortage, said the drugmaker, was the sharp increase in U.S. syphilis infections in recent years—up nearly 75% since 2017, according to the Centers for Disease Control and Prevention (CDC)—which had increased demand for the drug.
Amid the shortage, the CDC is recommending that Bicillin be used only for pregnant patients or infants who have been exposed to or diagnosed with the infection (there is no alternative treatment for these groups). CDC’s guidelines go on to advise that everyone else be prescribed the antibiotic doxycycline for two to four weeks.
But increasingly, and relatedly, doxycycline is being used in another role that could help prevent at least some syphilis infections from occurring in the first place: as post-exposure prophylaxis, known as doxyPEP, to be taken in a single dose up to 72 hours after sex to prevent infection—of not just syphilis but also the STIs gonorrhea and chlamydia.
And that’s music to the ears of David Harvey, executive director of the National Coalition of STD Directors, which has posted an online doxyPEP toolkit. Harvey told TheBody, “Doxy as STI PEP comes at just the right time. Empowering people with the ability to take a single dose of doxycycline after sex gives us a new way to prevent infections that would require far more antibiotic doses to treat.”
The Background on doxyPEP
Data supporting the use of doxyPEP has been building the past few years. TheBody has reported on its efficacy and latest updates extensively. But doxyPEP got its biggest boost this April when the New England Journal of Medicine published a large National Institutes of Health (NIH)–funded study finding that doxycycline cut the incidence of syphilis, chlamydia, and gonorrhea by two-thirds “when tested among men who have sex with men (MSM) and transgender women who took the medication within 72 hours of having condomless sex,” according to the NIH press release about the study.
Study participants taking doxyPEP were compared to control participants not taking it. Among those in the study on PrEP to prevent HIV, STIs were diagnosed in about 10% of clinic visits by those who did doxyPEP versus nearly 32% by those not doing doxyPEP. Among those in the study already living with HIV, the rate of STI diagnoses was nearly 12% for those doing doxyPEP versus more than 30% for those not doing it. In both groups, more than 86% of those taking doxyPEP said they took it consistently within 72 hours of having condomless sex, and more than 71% said they never missed a dose.
“Given its demonstrated efficacy in several trials, doxyPEP should be considered as part of a sexual health package for men who have sex with men and trans women if they have an increased risk of STIs,” said Annie Luetkemeyer, M.D., a co–principal investigator of the study.
A concern about doxyPEP has been the risk of users developing doxycycline resistance. In the NIH-funded study, more resistance to tetracycline (from which doxycycline is derived) was found in gonorrhea strains among those in the doxyPEP group than those in the non-doxyPEP group. “This suggests that doxyPEP may offer less protection against gonorrhea strains that are already tetracycline-resistant and that wider population-based surveillance for this type of resistance is important,” said the press release. (However, it should be noted that another drug, ceftriaxone, is used to treat gonorrhea, meaning that resistance to tetracycline would not prevent proper treatment of the infection.)
Amid the evolving data on doxyPEP, the CDC has issued considerations for prescribing doxyPEP—including a note that thus far we have data on its use only in folks assigned male at birth [cisgender gay and bisexual men and transgender women], with studies in cisgender women ongoing. But the CDC has not gone so far as to issue formal guidelines, which many providers wait for as a green light to begin prescribing. A CDC rep told TheBody that draft CDC guidelines would likely be posted for public comment by summer’s end.
Moving Forward With Treatment
Nonetheless, many of the country’s top LGBTQ health centers are already offering doxyPEP to patients who fit the data profile so far, primarily gay men and transgender women who report two or more condomless episodes of anal or oral sex, including those on PrEP or HIV treatment.
Boston’s longtime Fenway Health, for instance, issued doxyPEP guidelines to its providers in January. “We tell patients, ‘Hey, you fit the criteria we have for this new option that could help decrease the chance of getting syphilis, gonorrhea, and chlamydia,’” said Ami Multani, M.D., a Fenway medical director. According to Ken Mayer, M.D., Fenway’s medical research director, more than 45 providers had prescribed doxyPEP at least once by June’s end to more than 700 patients, with most of them already on PrEP and about 10% of them being patients living with HIV. No issues with either adherence or resistance had been seen yet, said both doctors.
In Maryland, the Chase Brexton health centers have issued prescribing guidelines to providers, said Amit Dhir, M.S.N., NP-C, who manages the sites’ PrEP and STI clinics. But he added that patients who’d heard about doxyPEP on social media or via friends were already asking for it. He said the centers had not yet tracked how many patients it’s been prescribed to, but he noted that the NIH-funded study showed that resistance mainly occurred in people who already had strains of drug-resistant gonorrhea—suggesting that the resistance was not caused by doxyPEP.
In short, he said, “If a patient asks me for doxyPEP, I don’t refuse it.”
Additionally, both Mayer at Fenway and Dhir at Chase Brexton said that they had robust long-term supplies of Bicillin; hence, the federal guidelines to withhold Bicillin in most cases of syphilis were not currently applicable to them.
That, too, is the case at New York City’s Callen-Lorde LGBTQ health clinics, where Marcus Sandling, M.D., the clinical director of sexual health, said that the center was taking its cue from the doxyPEP protocol issued by the San Francisco Department of Public Health, which, with University of California at San Francisco (UCSF), was a partner on the NIH-funded study.
Callen-Lorde, said Sandling, is offering PrEP to patients who’ve had an STI in the past year or who present the above-mentioned risk factors. “But in general,” he added, “we tend not to say no to any patient who is aware of doxyPEP and asking for it.” In the past few months since Callen-Lorde formalized its doxyPEP efforts, he said, he’s personally prescribed it to about 25 patients but has discussed it with far more. “We’re at the point now where people are regularly telling friends about it,” he said, much in the way that PrEP awareness has spread in the past decade, often via friend networks.
He added that he was keenly following news of resistance, noting that doxyPEP use was likely still only modestly expanding the use of doxycycline, which is inexpensive and widely used to treat many things, including Lyme disease. Still, he noted, “whenever you add more antibiotics to a community, the risk of resistance goes up,” and hence he’s keenly following data about doxyPEP resistance, he said.
Meanwhile, in Chicago, Wren O’Kelley, a rep for Howard Brown health center, told TheBody that in June through mid-July, the center had prescribed doxyPEP to at least 60 patients. “We’re seeing a significant increase in new prescriptions for doxyPEP based on word of mouth and provider recommendation alone,” O’Kelley said. The center is planning to launch an advertising campaign about it soon, but even now, “we’ve preliminarily seen a pretty strong positive response, and we expect that these numbers will continue to climb as more people learn it’s an option.”
O’Kelley also said that the center’s clinical leadership was discussing using doxycycline as a syphilis treatment alternative to Bicillin due to the Bicillin shortages, but they had not yet come to a final decision.