Research in context
Evidence before this study
Antibiotic prophylaxis has been used for decades as a biomedical intervention to contain the spread of sexually transmitted infections (STIs) in high-risk individuals. Early studies in the 1940s were done in the navy to assess the benefit of post-exposure prophylaxis (PEP) with sulfonamides or penicillin for gonorrhoea, but this approach was associated with rapid selection of antibiotic resistance. Similar results were observed in the 1980s with minocycline PEP for gonorrhoea, showing limited effectiveness in men exposed to gonococci resistant to minocycline. This strategy was subsequently abandoned. More recently, antibiotic prophylaxis for STIs has been assessed as a way to reduce the risk of HIV acquisition in female sex workers in developing countries by use of monthly periodic presumptive treatment with azithromycin. This strategy was associated with a modest reduction in the incidence of gonorrhoea and chlamydia but not of syphilis or HIV. Following the implementation of pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV acquisition in men who have sex with men (MSM), high rates of STIs have been reported in this population. We searched PubMed for articles published until Sept 8, 2017, using the terms “antibiotic”, “prophylaxis”, “men”, and “trial”, along with “STIs”, “gonorrhoea”, “syphilis”, or “chlamydia”. We reviewed 60 publications and identified two studies, one reported by the US military in 1979 on the use of minocycline PEP to prevent gonorrhoea but with no data for chlamydia or syphilis and another randomised trial of 30 HIV-infected patients involving daily doxycycline prophylaxis or incentive payments, which showed decreased incidence of STIs with antibiotic prophylaxis.
Added value of this study
This study is, to our knowledge, the first large, open-label, randomised trial assessing the efficacy and safety of a novel antibiotic PEP strategy for STIs involving doxycycline (200 mg taken within 24 h after sex) in MSM taking PrEP for HIV prevention. This study showed a high rate of STIs without prophylaxis, the majority of which were asymptomatic, but this antibiotic strategy showed significant benefit, with an overall 47% relative reduction in the incidence of a new STI. Although no clear benefit was shown for gonorrhoea, probably because of the already high rate of doxycycline resistance, a significant relative reduction in the incidence of chlamydia and syphilis was observed. The median use of doxycycline was 680 mg per month, with a good safety profile apart from an increased rate of gastrointestinal adverse events compared with PrEP alone.
Implications of all the available evidence
The results of this doxycycline PEP study for STIs in high-risk MSM taking PrEP show that this strategy can reduce the incidence of chlamydia and syphilis in this population with a good safety profile. Additional studies are needed to assess the full effect of this strategy on the selection of antibiotic resistance for gonorrhoea, syphilis, and chlamydia. Selection of tetracycline resistance remains an important potential risk of doxycycline PEP; we could not assess this risk because of the sample size and the relatively short period of follow-up. Pending additional studies, the use of doxycycline as PEP should be restricted to research purposes. In the future, this strategy might become an effective addition to a combined intervention approach to reduce the high rate of STIs in PrEP users.