Results from two small studies presented at the International AIDS Conference (#AIDS2024) in Munich in July showed that doxycycline pre-exposure prophylaxis (doxyPrEP) can effectively prevent sexually transmitted infections (STIs) when taken before sex.
The antibiotic doxycycline has been around for nearly six decades and is commonly used to treat various bacterial infections, but its use for prevention is relatively new. There is a large and growing body of evidence showing that doxycycline, taken within 72 hours after sex—a strategy known as doxyPEP—can prevent bacterial STIs, and even lower the rates of STIs community-wide. In June, the Centers for Disease Control and Prevention issued guidelines for doxyPEP to reduce bacterial STIs among gay and bisexual men and transgender women.
Two studies presented at AIDS 2024 suggest that DoxyPrEP could provide similar benefits.
DoxyPrEP led to an 80% reduction in STIs for MSMs
Dr. Troy Grennan (photo: The University of Columbia British)
Troy Grennan, MD, MSc, a clinical associate professor at the University of British Columbia, shared findings of a randomized controlled trial that studied the efficacy, tolerability, and use patterns of doxyPrEP. The trial included 52 men who have sex with men, all living with HIV and having a history of syphilis, in Toronto and Vancouver, Canada. The men were randomized to receive either a daily dose (100mg) of doxycycline or a placebo. Adherence was measured through blood tests to measure the amount of doxycycline, and researchers concluded nearly 80 percent took the medication throughout the trial period.
The outcomes were significant and in line with studies showing the efficacy of doxyPEP. Among the 41 (78.8%) participants who finished the 48-week study, there was a 79% reduction in syphilis, a 92% reduction in chlamydia and a 68% reduction in gonorrhea in the doxycycline arm compared to the placebo arm. The trial controlled for any differences in drug adherence or sexual behaviors. Three participants developed resistance to doxycycline, but Brennan said that because the number of people who developed resistance was small, it was hard to draw any definitive conclusions.
The researchers also looked at tolerability and side effects and found no difference between the doxyPrEP and placebo arms, Grennan said at a press conference held before AIDS 2024. “People often prefer to take a pill daily [for STI prevention] because they're already taking pills for other reasons,” he said.
The findings support further evaluation of doxyPrEP compared to doxyPEP in an ongoing larger trial, he said, and to that end, he added that his team started recruiting people for a larger, nationwide DoxyPrEP trial and plan to have more than 500 participants by the summer of 2025.
Right now, doxyPrEP isn’t the standard of care for people who are most vulnerable to bacterial STIs, but Grennan thinks it should be. “I think it's reasonable in many situations to prescribe [doxycycline] if it's indicated, as long as you're having a reasonable conversation with your patients about the pros and the cons and the unknowns,” he said.
“I think we need to move this research towards… other key populations like cisgender women and youth who are always ignored in STI and HIV research. And we need to do some work on implementation of these interventions in an equitable way.”
It should be noted that the CDC’s guidelines for doxyPEP were limited to men who have sex with men and to trans women because a recent clinical trial of doxyPEP among cisgender women in Kenya did not demonstrate any benefit.
Syphilis vanished for female sex workers on doxyPrEP
A second study presented at AIDS 2024, however, showed a significant benefit for cis women who took doxyPrEP. Researchers looked at the feasibility, tolerance and efficacy of doxycycline for STI prevention for female sex workers (FSW) in Tokyo, Japan. In this year-long retrospective cohort study, which started in October, 2022, 40 FSWs with a median age of 29 years were selected from a larger group of 96 who sought care at a private STI clinic. Researchers were looking for the difference doxyPrEP made in the rates of Chlamydia trachomatis, Neisseria gonorrhoeae, and syphilis. All women were offered a choice of doxyPrEP (100 mg daily) or doxyPEP. Six of 96 chose to take only post-sex (PEP) doses, and were excluded from the study, as were 50 women who did not take STI tests either before or after starting doxycycline.
Though there was no placebo group, researchers studied the efficacy of doxyPrEP by comparing incidence rates (per 100 person-years) before and during doxyPrEP use. They also examined abnormalities and antimicrobial treatment in the vaginal microbiome through microscopic examination of vaginal smears every 1–3 months. The team used surveys to measure adverse events and user satisfaction.
Almost all participants adhered strictly to doxyPrEP and none reported severe adverse events related to doxycycline, according to presenter Seitaro Abe of the National Center for Global Health and Medicine in Japan. Notably, most of the women—95%—used condoms, both before and during the study. In surveys, nearly three-quarters of participants said they had less anxiety about acquiring STIs while on doxyPrEP.
There was a notable reduction in STIs. Before doxyPrEP, the overall STI incidence rate was 232.3 per 100 person-years among the 40 participants. After initiating doxyPrEP, the overall rate of all STIs declined to 79.2 per 100 person-years. The most stunning finding was that syphilis incidence vanished: an 8% annual incidence rate prior to taking doxycycline turned to zero infections.
The findings translated to an average efficacy across all three STIs of 67%. In terms of STI incidence, the rate for all three STIs fell from 108 to 18 new cases. For chlamydia, the rate fell from 74 to 13 cases; gonorrhea fell from 26 to five cases. Syphilis dropped from eight new cases to zero. Abe said the reduction in chlamydia was “marginally significant,” but the reduction in the incidence of gonorrhea was not statistically significant.
There was also a reduction in bacterial vaginosis, from 36 to 23 cases, as well as candidiasis, from 18 to 12 cases.
In follow-up interviews, nearly one out of four reported occasional nausea and vomiting, but no serious doxycycline-related adverse events. And even when they experienced nausea, among the 22 women who completed surveys, 73% never missed a dose, even on days they didn’t have sex, according to Abe.
Abe concluded saying the research supports the use of doxyPrEP by people who are vulnerable to STIs.”
In an email, Abe offered a possible explanation for why doxyPEP provided no benefit for cis women (in Kenya) while doxyPrEP did prevent bacterial STIs in cis women in Tokyo: adherence. “I expect that if [the doxyPEP Kenya study] could overcome adherence challenges, significant results would be observed. In our study, we did not measure doxycycline concentrations, but the observed prevention of bacterial STIs suggests that adherence was not a significant issue. If there were no effects, we might suspect adherence problems, but this was not the case here.”