Instead of simply treating sexually transmitted infections with antibiotics, a new public-health movement seeks to use one such medication to prevent STIs in the first place. Promising research into variations on this method has raised hopes, but also concerns about whether this method might also contribute to another public health crisis: drug-resistant infections.
One thing is clear: The nation is in dire need of game changers to battle the STI epidemic, as gonorrhea, chlamydia and syphilis have largely soared during the past decade.
Syphilis, which public health experts thought as recently as the 1990s could possibly be eliminated, has seen especially worrying increases among pregnant women in particular. Congenital syphilis — when a mother passes the infection to her baby — can be fatal or lead to severe birth defects.
Enter doxycycline: a common, well-tolerated antibiotic long used for multiple purposes, including treating acne.
Last month, the Centers for Disease Control and Prevention issued guidelines for the use of doxycycline after sex — as post-exposure prophylaxis, or doxyPEP — to lower the risk of bacterial STIs among gay and bisexual men and transgender women. The recommendation was limited to this population because a recent clinical trial of doxyPEP among cisgender women failed to demonstrate any benefit. Men who have sex with men also have a disproportionately high STI rate.
The CDC endorsement followed three randomized controlled trials finding that providing doxycycline to gay and bisexual men and trans women and instructing them to take one 200-milligram dose within 72 of sex lowered their risk of chlamydia and syphilis by more than 70% and gonorrhea by about 50%. Further research of the gay community’s use of doxyPEP in San Francisco has been similarly promising.
“It’s too early to know whether doxyPEP will reverse years of increasing STIs,” said Dr. Jonathan Mermin, the CDC’s STI-prevention director. “However, there is considerable enthusiasm in the community and by many providers.”
Now, two new studies have helped expand the conversation about doxycycline, to ask whether taking just 100 mg of the antibiotic daily — as pre-exposure prophylaxis, or doxyPrEP — might afford a more optimal balance of risks versus benefits for some people.
Findings from these studies, conducted among HIV-positive gay and bisexual men in Toronto and Vancouver, British Columbia, and in female sex workers in Tokyo, will be presented at the 25th International HIV Conference in Munich, Germany, which runs July 22-26.
“I have had some patients prefer the once-a-day, adding the pill to their daily medication routine and not worrying about when or how to take it after sex,” Dr. Jeffrey Klausner, a professor of infectious disease at the University of Southern California, said of the doxyPrEP protocol. “Other patients prefer the single dose after sex — simple and easy.”
Klausner was not involved in the new studies, but he was the lead author of the first-ever doxyPrEP study, of a small group of gay and bisexual men in Los Angeles. Published in 2015, it found that those in the doxyPrEP group were less likely to be diagnosed with STIs than those provided financial incentives to remain STI free.
The main concern about prescribing doxycycline for prevention is that it might drive the emergence of drug-resistant infections, like staph. Gonorrhea is the only of the three STIs with documented acquisition of such resistance. But while doxycycline is proven effective at preventing gonorrhea, it isn’t generally used to treat that infection.
On the flip side, by reducing STI rates, doxycycline can lessen the need for other antibiotics to treat such infections — thus lowering the potential that those drugs can drive drug resistance.
The new double-blind Canadian study of doxyPrEP enrolled 52 gay and bisexual men and evenly randomized them to receive doxycycline or a placebo. After one year, the doxyPrEP group had a 68% to 92% lower diagnosis rate of each of the three STIs — a comparable result to the recent doxyPEP study.
There was essentially no difference in drug-resistance among staph infections between the two groups, albeit from a very small number of samples.
In the Japanese study, 40 women in the commercial sex trade saw their STI infection rate decline by two thirds, from about 225 diagnoses per 100 cumulative years of follow-up before receiving doxyPrEP to a rate of about 80 diagnoses afterward. Once the women were prescribed daily doxycycline, syphilis vanished among them. Chlamydia declined by about two thirds, but this shift was only marginally statistically significant. There was no significant change in gonorrhea.
The study authors found no change in signs of drug resistance in two infections: bacterial vaginosis and Candida vaginitis.
Nearly three quarters of the women reported reduced anxiety about contracting STIs.
“It is important to emphasize that these are both small studies,” Dr. Christoph Spinner, local co-chair for the forthcoming HIV conference and chief medical information officer at University Hospital rechts der Isar in Munich, said at a recent press briefing. “Also, the one from Canada is a pilot study, and the one from Japan had no control group.”
A more enthusiastic Klausner reflected on the results of the study of gay men and said that they “are compelling and support the idea that people should have choice” in their STI prevention tools. “Current guidelines might need to be further updated.”
Dr. Troy Grennan, the physician lead for the provincial HIV/STI program at the BC Centre for Disease Control in Vancouver and the lead author of the study in gay men, said his findings support the nationwide trial in Canada that his research team launched a year ago comparing doxyPEP with doxyPrEP. The study has enrolled about 150 of a planned 560 participants.
“The generic blanket statement of saying that doxyPEP is better because it’s less drug — we can’t assume that is the bottom line,” he said.
For one thing, some people may have sexual partners frequently enough that it makes more sense to take doxycycline daily as PrEP — both because at half the dose of doxyPEP, doxyPrEP actually adds up to less overall use for them. Also, consistent rather than intermittent exposure to antibiotics may lower the risk of the emergence of drug resistance in pathogens.
And for some people, especially those who already take daily medications, such as pills to treat or prevent HIV, it’s easier to remember to take a daily pill than to schedule doses based on the timing of recent sexual encounters.
As for the worry of promoting drug resistance, “The trend hasn’t really been convincing one way or another,” Grennan said. Research seeking to address this question is ongoing.
Like Klausner, Grennan touted the benefits of choice in STI prevention tools among those at risk.
“One size does not fit all,” he said.
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