Three days after sexual contact, doxycycline post-exposure prophylaxis reduced the incidence of gonorrhea, chlamydia, and syphilis.
A study presented at the 24th International AIDS Conference in Montreal found that taking the antibiotic doxycycline within 72 hours of sex dramatically reduced the incidence of gonorrhea, chlamydia, and syphilis in gay men and transgender women living with HIV or on pre-exposure prophylaxis (PrEP).
According to study author Annie Luetkemeyer, MD, of the University of California at San Francisco, “using doxycycline following condomless intercourse shows potential as an effective technique to considerably reduce sexually transmitted infections in selected populations with persistent high rates of STIs.”
“Both #UequalsU and #PrEP have changed things… condomless sex is happening and we need to make it safer.”@aidsmap writer @LizHighleyman spoke with Professors Annie Luetkemeyer and Connie Celum about #DoxyPEP to prevent STIs.pic.twitter.com/j6Z0QS6u8C
— Matthew Hodson (@Matthew_Hodson) August 5, 2022
At an AIDS 2022 media event, she stated, “This isn’t meant for everyone.” But there are communities that are genuinely suffering from the STI pandemic, and it’s time to act on the evidence and seriously consider putting it into guidelines and implementing this in a careful and safe manner.
PrEP significantly lowers the chance of contracting HIV, but not using condoms puts people at risk of contracting other STDs (STIs). Guidelines advise screening for bacterial STIs in PrEP users every three months, allowing for quick treatment, but it would be preferable to avoid them altogether. The French IPERGAY trial, which assessed on-demand PrEP, previously offered circumstantial support for the idea that doxycycline post-exposure prophylaxis (PEP) lowers STI incidence.
David Harvey, executive director of the National Coalition of STD Directors (NCSD), stated in a statement that “these are the kinds of advances clinicians, patients, and communities badly need to help fight the epidemic of STIs in the United States.” Our conclusion from the DoxyPEP research is that we are moving toward a day when some of our patients and highest-risk neighbors may not even need to worry about symptomatic infection or community transmission.
At public health clinics in San Francisco and Seattle, more than 500 males and transgender women who have sex with men were enrolled in the DoxyPEP trial. A total of 4% of them identified as trans women or “gender variant.” 327 people were on PrEP, and 174 were HIV positive. 38 years old on average, 67% white, 30% Latino, 11% Asian/Pacific Islander, and 8% black people made up the population.
The study cohort was very susceptible to subsequent STIs. They reported having had a median of nine sex partners in the previous three months, and about 60% disclosed recent substance use. They had received a STI diagnosis within the previous year (69% with gonorrhea, 58% with chlamydia, and 20% with syphilis).
The patients were randomized in a 2-to-1 ratio to receive either the standard of therapy, which is routine testing and treatment after diagnosis, or a single 200-milligram dosage of oral doxycycline PEP within 72 hours of condomless sex (not to exceed one dose in a 24-hour period). Every three months, they underwent gonorrhea, chlamydia, and syphilis tests.
An intermediate analysis revealed that doxycycline PEP considerably lowers the incidence of STIs, prompting the study’s early termination one year before its original May 2023 completion date.
Doxycycline PEP decreased the risk of being diagnosed with a bacterial STI by 62% among participants with HIV compared to standard-of-care (incidence of 11.8% versus 30.5%, respectively). When gonorrhea, chlamydia, and syphilis are considered separately, the incidence of each STI decreased from 20.3% to 8.9%, a 57% decrease, a 74% decrease, and a 77% decrease, respectively.
For people using PrEP who tested HIV-negative, the risk reduction was much larger. Comparing this group to the standard-of-care group (10.7% versus 31.9%), there was a 66% decrease in the number of new STIs per quarter in this group. Chlamydia decreased from 12.1% to 1.4% (a reduction of 88%), gonorrhea decreased from 20.2% to 9.1% (a reduction of 55%), and syphilis decreased from 2.7% to 0.4% (a reduction of 87%).
Doxycycline PEP was safe, well-tolerated, and had strong adherence in both groups. A median of seven sex acts per month were reported by the subjects, 87% of which were covered by doxycycline. More than half (54%) said they took fewer than 10 dosages per month, 30% said they took between 10 and 20, and 16% said they took more than 20.
Only 1.5% of participants (88%) reported they had stopped taking doxycycline because of intolerance or personal preference. No substantial adverse effects or anomalies in the lab were reported.
Doxycycline PEP Concerns
The potential development of medication resistance due to antibiotic overuse is a serious worry with doxycycline PEP. The majority of drugs previously used to treat gonorrhea do not work on it anymore. About 20% of the subset of gonorrhea samples examined in this study initially shown resistance to the related antibiotic tetracycline, which is comparable to the rate in the U.S. population, but this resistance increased over time in the doxycycline PEP group.
Since gonorrhea and syphilis are not common conditions that doxycycline is used to treat, patients who do develop resistance to it have access to other treatments. Additionally, weeks or months of using a lower daily dose of doxycycline have not led to the development of resistance when used to prevent malaria in tourists.
Frequent antibiotic use raises the possibility of affecting the microbiome, the ecosystem of good bacteria that often resides in the vagina, the gastrointestinal tract, and other parts of the body. Analyses of resistance and the microbiota are ongoing.
Leutkemeyer pointed out that individuals in the control group nonetheless spent a significant amount of time on doxycycline treatment since they contracted STIs so frequently. Doxycycline as PEP minimizes symptoms, eases pain, and shortens the period of time during which STIs can spread among people. In fact, she added, some patients took doxycycline frequently enough—almost daily, if they frequently engaged in sexual activity—that it was likely acting as STI PrEP.
Doxycycline PEP accessibility could be a problem. Before it was approved, some gay men were already using it for this indication, but supporters questioned if it would help everyone. Ten years after its approval, White gay men are still using PrEP more frequently than Black and Latino gay men, but the difference is widening. Doxycycline comes in affordable generic forms, but if someone uses it frequently, the expense may mount.
Doxycycline PEP may also be beneficial for cisgender women and transgender males, but these populations have not yet been researched. An investigation on cisgender women in Kenya is under underway, and results should be available next year, according to DoxyPEP investigator Connie Celum, MD, MPH, of the University of Washington.
The National Center for HIV/AIDS Surveillance and Prevention (NCSD) is working to inform STI programs about the DoxyPEP results and aims to provide the CDC with advice regarding local implications.
To ensure that patients receive the best care possible without having to wait, Harvey urged the CDC to update treatment recommendations right away.
The CDC stated it is “encouraged” by the preliminary statistics in a statement in response to the study’s findings.
“To create therapeutic guidelines on the safe and effective use of this method for bacterial STI prevention among homosexual and bisexual men and transgender women, further examination of the data given, and maybe other analyses, will be required. It will be crucial to offer advice that will optimize STI prevention effectiveness while limiting potential dangers to both individual and public health, the organization said. “We must act rapidly to put effective STI prevention programs into place. We cannot cut corners when it comes to people’s health, so it is our public health obligation to create reasonable counsel based on a rigorous analysis of all relevant evidence, risks, and benefits.
Doxycycline PEP provides a new tool to the safer sex repertoire, but some are concerned that it would encourage more condom-free sex, similar to what happened with HIV prevention tablets.
“When PrEP was introduced, we witnessed a lot of stigma and shame—why not just use a condom?—but we need a variety of resources. Leutkemeyer added, “I’m hoping this won’t come with the humiliation and stigma that came with the first round of PrEP.
Damon Jacobs, a longtime supporter who founded the PrEP Facts Facebook group, told POZ that the “[DoxyPEP] results confirm the harm reduction strategies that many of us on PrEP have already embraced.” “We have the right and the capacity to take pleasure in sexual activity while reducing risk at the same time.”
Click here to read the study abstract.
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