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Doxycycline prophylaxis for syphilis and chlamydia has shown promising results in initial trials among men who have sex with men (MSM), with ongoing research hoping to tease out more benefits, an evidence review found.

While two randomized trials already showed about 70% efficacy for both doxycycline pre- and post-exposure prophylaxis, modest sample sizes have yielded "imprecise effect sizes," reported Jeffrey Klausner, MD, of UCLA David Geffen School of Medicine and Fielding School of Public Health in Los Angeles, and colleagues.

However, research currently being conducted hopes to better pinpoint drug regimen, which populations to focus on, and tolerability and efficacy in a real-world setting, they wrote in .

Researchers pointed to the success of HIV pre-exposure prophylaxis (PrEP) as showing that "biomedical interventions for STI [sexually transmitted infection] prevention can be effective, safe and highly acceptable" when talking about how to combat the increasing incidence of STIs over the past 2 decades. Historically, they added that there were anecdotal reports of doxycycline used for syphilis prophylaxis during the Vietnam War among U.S. and Australian soldiers, and that the antibiotic is used as a first-line agent for chlamydia treatment, and an alternative regimen for syphilis.

An international group of researchers met in Seattle in March to review the evidence before conducting the literature review, the authors said. They started with the small existing trials for doxycycline as PrEP or post-exposure prophylaxis. A small open-label study of MSM with HIV and prior syphilis infection randomized to doxycycline found a reduction in Chlamydia trachomatis, Neisseria gonorrhoeae, and syphilis versus a control group.

The second study was an open-label extension of the French IPERGAY study, best known for examining in MSM. This study found that HIV-uninfected MSM and transgender women randomized to doxycycline post-exposure prophylaxis following condomless anal sex encounters had a lower incidence of chlamydia and syphilis diagnoses. A modeling study among Australian MSM discovered that if doxycycline post-exposure prophylaxis was 70% effective, syphilis could decrease by 50% after 12 months, and up to 85% after 10 years.

Currently, a variety of studies are examining doxycycline prophylaxis, the authors said. The randomized 50 HIV uninfected MSM to immediate doxycycline PrEP or delayed initiation after 6 months, with 1 year of daily HIV PrEP. So far, there have been no STIs in patients on immediate doxycycline PrEP and three cases of C. trachomatis in the delayed arm, the authors said.

Other studies that plan to study this issue include:

• The in Australia among HIV infected and uninfected MSM and transgender women with a history of regular STI testing using doxycycline PrEP to determine efficacy and tolerability of daily use
• A French sub-study within the ANRS Prevenir PrEP cohort examining doxycycline as post-exposure prophylaxis to prevent chlamydia and syphilis infection in participants with a prior STI diagnosis versus no doxycycline PEP
• A U.S. study of HIV infected and uninfected MSM and transgender women with at least one bacterial STI and one episode of condomless sex with at least one male partner in the last year randomized to doxycycline as post-exposure prophylaxis following each condomless sex act versus standard of care

But several unanswered questions remain. At the 2018 International Conference on HIV Drug Therapy (HIV Glasgow), IPERGAY investigator and current co-author Jean-Michel Molina, MD, of the University of Paris Diderot, said that "we have to wait for additional studies to assess the benefit/risk ratio" of antibiotic prophylaxis for STIs.

Indeed, the authors raised several questions about efficacy, including optimal dose (100 mg daily or 200 mg single dose post-condomless sex act), and which specific sex acts were protected. They also discussed which populations might derive the most benefit from doxycycline prophylaxis, noting that an Australian study suggested focusing on MSM with >20 sex partners in 6 months. Safety would also be a concern, with gastrointestinal side effects reported most frequently.

The authors also cited the potential problem of antimicrobial resistance, noting that there would be a need to develop "consistent laboratory methods" to evaluate resistance of various STIs to doxycycline.

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