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When will I be able to take a pill to prevent gonorrhea, syphilis and chlamydia?

, by Emily Land

BETA is reporting from the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Seattle—bringing you the latest news, updates, and research on HIV treatment and prevention.

The World Health Organization estimates that every day, more than 1 million sexually transmitted infections (STIs) are acquired around the globe, with a grand total of 357 million new cases of curable STIs (chlamydia, syphilis, gonorrhea and trichomoniasis) occurring every year. And in many places, including San Francisco, STI rates are on the rise. Just as we are able to take a daily medication to prevent HIV, will it ever be possible to take a medication to prevent these pesky, and sometimes dangerous, STIs?

Jean-Michel Molina

Jean-Michel Molina (Photo: BETA)

That was precisely the subject of a well-attended symposium talk delivered at CROI last night by Jean-Michel Molina, from the University of Paris Diderot. Introducing the topic, he thanked the conference organizers to asking him to speak about a subject he described as “interesting, and quite controversial.”

History of STI prophylaxis—it’s not a new idea!

Preventing STIs with post-exposure prophylaxis or daily prophylaxis is an idea (and strategy) that goes back years. Molina shared a handful of interesting research papers, published as far back as 1943, where physicians demonstrated the success of orally-delivered sulfathiazole to prevent gonorrhea (JAMA, 1943); oral penicillin to prevent gonorrhea (Public Health Reports, 1948); oral minocycline given after exposure to gonorrhea to prevent infection (NEJM, 1979); and an injection of penicillin given after exposure to syphilis to prevent infection (JAMA, 1971).

Molina also shared the results of two more recent studies with female sex workers, who were provided with once-monthly antibiotic prophylaxis. The first study, by Kaul and colleagues (JAMA, 2004), provided oral azithromycin (or a placebo) once a month for more than two years. Women taking the antibiotic had a significantly lower incidence rate of trichomoniasis, gonorrhea and chlamydia than women in the placebo group.

A second study, conducted by Steen and colleagues (AIDS, 2012) provided monthly doses of azithromycin + cefixime/ciprofloxacin to female sex workers, a regimen which reduced the incidence of gonorrhea and chlamydia by 50%. There was no evidence of risk compensation or antibiotic resistance, but surveillance for this was described by Molina as “inadequate.”

Current STI prophylaxis research with gay men

A more recent study, by Bolan and colleagues (Sexually Transmitted Diseases, 2015), found that a daily dose of doxycycline prevented gonorrhea, syphilis and chlamydia infection in a small group of men. There are two currently ongoing trials with doxycycline for the prevention of STIs in men who have sex with men: One is enrolling men living with HIV with a history of prior syphilis, and the other is enrolling HIV-negative men on HIV PrEP.

“Superbugs,” and other possible problems of STI prophylaxis

“The most feared adverse consequence of antibiotic prophylaxis by far is the selection of antibiotic resistance,” said Molina. “Not only the selection of antibiotic resistance, but the clonal dissemination of drug-resistant STIs.” At this point in time, said Molina, we already have limited treatment options for some STIs, and for gonorrhea in particular.

“Every time we’ve used an antibiotic to treat or prevent gonorrhea, these bacteria have been able to develop resistance shortly thereafter. What we are fearing now, with gonorrhea, is to face untreatable gonorrhea in the future. We’re not there yet, but we have to be cautious with antibiotics used for treatment or prevention,” said Molina.

Chlamydia, however, is a bit different. So far, there have not been any reports of drug-resistant chlamydia infections in humans—although there has been a report of a drug-resistant chlamydia suis strain detected in pigs. (Farm animals are oftentimes treated prophylactically with antibiotics to prevent infections, which may have allowed this drug-resistant strain of chlamydia to develop.)

The bacteria that causes syphilis (treponema pallidum) is susceptible to the drug penicillin—even through the drug has been used for more than six decades. This may be because, in order for resistance to develop, you need multiple mutations to develop, which hasn’t happened yet.

Antibiotic therapy also may have a negative impact on the human microbiome (the colonies of bacteria, oftentimes “good” bacteria, that colonize our gut and other places in and around our bodies) or facilitate the emergence of STIs that delay their incubation period (i.e., that don’t show symptoms right away).

The take-away

Antibiotic prophylaxis for STIs, even while highly successful in the short term, usually only provides transient benefits, said Molina. Importantly, antibiotics are not currently recommended as prophylaxis for STIs.

“The results of ongoing trials should be carefully analyzed,” he cautioned. “It would be premature at this point in time to recommend any implementation of prophylaxis until we have results from ongoing trials. Like with any prescription of antibiotics, the short-term benefits should be weighed against the long-term consequences for the community.”

During a Q&A at the end of the talk, Molina highlighted the idea that, in the future, prevention might look very different for different STIs. Preventing gonorrhea with antibiotics, because of the risk of developing drug-resistant strains, might not be a good idea. Whereas it might be more possible to develop antibiotic prophylaxis for chlamydia and syphilis.

“All these data suggest that we need to foster research in STI prevention and to develop vaccines for bacterial STIs.”

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