Postexposure Doxycycline is shown to prevent bacterial STIs
The prevalence of sexually transmitted infections has significantly increased in recent times. A total of 2.53 million cases of chlamydia, gonorrhea and syphilis were recorded in 2021, according to the Centers for Disease Control and Prevention (CDC) [1]. This has led to a pressing need for effective interventions. Emerging studies propose that a commonly accessible antibiotic, when used post-intercourse, could potentially play a crucial role in reducing the escalation of this issue.
Old Drug, New Indication
New research shows taking Doxycycline, after unprotected sex greatly reduces the chances of developing STIs such as syphilis, chlamydia and gonorrhea among men who have sex with men (MSM) and transwomen (TGW). The dosage regimen evaluated was a single dose of Doxycycline 200 mg administered within 24-72 hours of unprotected sex.
2017 ANRS IPERGAY Trial
A study in 2017 assessed whether postexposure (PEP) with doxycycline could reduce the incidence of STIs in 232 MSM participants. Participants were randomly assigned to take a single oral dose of 200mg Doxycycline PEP within 24h after unprotected sex or no prophylaxis. Participants were then followed up for a median of 8.7 months.
Efficacy
It was found that Doxycycline PEP significantly reduced the first occurrence of:
- an episode of chlamydia (HR 0.30; 95% CI 0.13-0.70; p=0.006);
- an episode of syphilis (HR 0.27; 95% CI 0.07-0.98; p=0.047);
- but not an episode of gonorrhea (HR 0.83; 95% CI 0.47-1.47; p=0.52).
Safety
The rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0.05) [2].
Recent Supporting Data
The results from the 2017 ANRS IPERGAY Trial were corroborated by another recent study presented. In this open-label, randomized study, a total of 501 MSM and TGW participated. The primary endpoint was the incidence of at least one STI per follow-up quarter.
Efficacy
Using a single, oral dose of doxycycline 200mg within 72 hours after unprotected oral, anal, or vaginal sex in MSM and TGW, who were either persons living with HIV (PLWH) or taking HIV pre-exposure prophylaxis (PrEP), showed significant reductions in chlamydia, gonorrhea, and syphilis per quarter of study follow up.
The % reduction in STIs after taking doxy-PEP in the two groups studied:
| Syphilis | Chlamydia | Gonorrhea | |
| HIV PrEP | 87 (95% CI, 0.03-0.59) | 88 (95% CI, 0.05-0.25) | 55 (95% CI, 0.32-0.65) |
| PLWH | 77 (95% CI, 0.04-1.29) | 74 (95% CI, 0.12-0.57) | 57 (95% CI, 0.26-0.71) |
Safety
One grade 2 laboratory abnormality (transaminitis) and five grade 3 adverse events (three diarrheal events and two headaches or migraines) were attributed to Doxycycline. No serious adverse events were attributed to Doxycycline.
Antimicrobial Resistance
The effect of prophylactic antibiotic strategies on antimicrobial resistance is an important consideration. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 (38%) in the Doxycycline groups and 2 of 16 (12%) in the standard-care groups. However, cultures were limited due to an inability to collect cultures before gonorrhea treatment in half the participants and a lack of culture growth, which is more common with extragenital gonorrhea.
S. aureus carriage was also 40% lower in the doxycycline groups than in the standard-care groups at 12 months. Among the participants with colonization, a modestly higher proportion had doxycycline resistance in the doxycycline groups than in the standard-care groups, which could have clinical implications, because doxycycline can be used to treat methicillin-resistant S. aureus skin and soft-tissue infections. However, there was not a substantial difference in overall doxycycline-resistant S. aureus isolated between the doxycycline groups and the standard-care groups (5% and 4%, respectively) [3].
The effectiveness data provide evidence for Doxy-PEP as an effective STI prevention that the data safety monitoring board advised the researchers to halt the trial and offer Doxycycline to all participants.
However, doxy-PEP’s role in other populations disproportionately affected by STIs warrants further research. In a study done on cisgender women in Kenya, Doxy-PEP proved ineffective in preventing STIs.
Doxy-PEP in Kenyan women
The study was an open-label 1:1 randomized trial of Doxy-PEP vs standard of care among 446 Kenyan women. Women were followed for 12 months, with quarterly STI testing, treatment, and adherence counselling. The primary trial outcome was the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups.
Efficacy
Using a single, oral dose of doxycycline 200mg within 72 hours of unprotected sex, incident STI events were detected at 109 follow-up visits (85 C. trachomatis, 31 N. gonorrhoea, including 8 with both; 1 T. pallidum): 50 among those assigned to Doxy-PEP and 59 among those assigned STI screening and treatment alone (RR 0.88, 95% CI 0.60-1.29, p=0.51).
Safety
There were no serious adverse events determined to be related to the use of doxycycline.
Study results show that among young cisgender women with high prevalence and incidence of STIs, the use of doxycycline PEP following sex did not reduce incident STIs. While the results were a huge disappointment, experts suggest that this may be because of anatomical differences in how the drug is metabolized or because of the high prevalence of antibiotic-resistant bacteria in Kenya [4].
Moving Forward
While CDC has acknowledged the use of Doxy-PEP, this only applies to gay, bisexual men and transgender women. Continued studies among heterosexual cis-gender women are required to determine whether Doxy-PEP is an effective and beneficial strategy for STI prevention.
In addition, there is currently no long-term data available regarding the impact of STI PEP on antimicrobial resistance and the microbiome. Evidence remains to be collected and reviewed for possible antimicrobial resistance among bacterial STIs, commensal Neisseria (as a potential reservoir for tetracycline-resistant plasmids), and S. aureus. The effects of Doxy-PEP on the gut microbiome are also being studied.
References:
- Centers for Disease Control and Prevention. U.S. STI epidemic showed no signs of slowing in 2021. Centers for Disease Control and Prevention. https://www.cdc.gov/nchhstp/newsroom/2023/2021-STD-surveillance-report.html
- Molina JM, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018;18(3):308-317.
- Luetkemeyer AF et al. Postexposure doxycycline to prevent bacterial sexually transmitted infections. N Engl J Med 2023; 388:1296.
- Stewart J, Bukusi E, Sesay FA, et al. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022;23(1):495. Published 2022 Jun 16.
