A new avenue to explore in STI prevention

The last 2 decades have seen considerable advancements in HIV care, with substantial improvements in HIV-related mortality and morbidity, affording many living with the virus a near-normal life expectancy.


The last 2 decades have seen considerable advancements in HIV care, with substantial improvements in HIV-related mortality and morbidity, affording many living with the virus a near-normal life expectancy. Paralleling these improvements, there have also been some concerning increases in bacterial sexually transmitted infections (STIs)—many of which disproportionately affect HIV-positive gay, bisexual, and other men who have sex with men (GBMSM).[1]

The current state of STIs
Syphilis disproportionately affects GBMSM, with the potential for significant sequelae—particularly in those who are HIV-positive.[2] Even in early infection, syphilis can cause significant complications including nervous system invasion.[3] Infections associated with Chlamydia trachomatis and Neisseria gonorrhoeae in GBMSM have also received significant attention in the last several years. One of the most urgent STI public health issues is the emergence of antimicrobial resistance (AMR) to gonorrhea. Resistance has been documented to most agents with activity against gonorrhea.[4] Another concern specific to GBMSM is lymphogranuloma venereum, caused by the certain serovars of C. trachomatis. It has become increasingly common among GBMSM in North America and Europe, with local transmission in Canada first noted in 2003.[5] Untreated, this infection often presents with hemorrhagic proctitis and can lead to lymphatic obstruction, strictures, and fistulas.[6]

A possible new STI prevention tool?
The convergence of effective HIV-prevention strategies and increases in STIs emphasizes the need for novel STI-prevention strategies to reduce STI-related complications. A recent pilot study by a group in California randomized 30 participants to receive either the antimicrobial doxycycline daily or a monetary incentive to remain STI-free throughout the study period.[7] After 48 weeks, those receiving doxycycline were significantly less likely to be diagnosed with any STI (odds ratio [OR] 0.27; 95% CI 0.09–0.83). Doxycycline also demonstrated efficacy specifically for preventing syphilis, though it was underpowered for this outcome (OR 0.24; 95% CI 0.04-1.33). Similarly, doxycycline has now been studied for STI postexposure prophylaxis (PEP) in HIV-negative GBMSM.[8] Participants were drawn from IPERGAY, a clinical trial of sexual-activity-based HIV pre-exposure prophylaxis (PrEP). In this study, individuals could take 200 mg of doxycycline within 72 hours of condomless sex (not exceeding six tablets per week). Overall, the incidence of STIs (specifically syphilis and chlamydia) was significantly reduced in those randomized to receive doxycycline (hazard ratio [HR] 0.53; 95% CI 0.33-0.85).

In the context of increasing STIs, the importance of thinking innovatively about STI prevention is clear. The use of doxycycline as an STI-prevention agent appears promising, and represents a novel tool for the STI-prevention armamentarium. Future studies—some of which will be led by these authors—will examine doxycycline’s use in a broader, more systematic way, focusing on analyses related to AMR and efficacy.
—Troy Grennan, MD, FRCPC
—Mark Gilbert, MD, FRCPC
—Mark Hull, MD, FRCPC

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.


References

1.    Ling DI, Janjua NZ, Wong S, et al. Sexually transmitted infection trends among gay or bisexual men from a clinic-based sentinel surveillance system in British Columbia, Canada. Sex Transm Dis 2015;42:153-159.
2.    Burchell AN, Allen VG, Gardner SL, et al. High incidence of diagnosis with syphilis co-infection among men who have sex with men in an HIV cohort in Ontario, Canada. BMC Infect Dis 2015;15:356. doi:10.1186/s12879-015-1098-2.
3.    Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64:1-137.
4.    Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Atlanta, GA: US Department of Health and Human Services; 2013.
5.    Totten S, MacLean R, Payne E, Severini A. Chlamydia and lymphogranuloma venereum in Canada: 2003-2012 summary report. CCDR 2015;41:20-25.
6.    Macdonald N, Sullivan AK, French P, et al. Risk factors for rectal lymphogranuloma venereum in gay men: Results of a multicentre case-control study in the UK. Sex Transm Infect 2014;90:262-268.
7.    Bolan RK, Beymer MR, Weiss RE, et al. Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: A randomized, controlled pilot study. Sex Transm Dis 2015;42:98-103.
8.    Molina JM, Charreau I, Christian C, et al. On demand post-exposure prophylaxis with doxycycline for MSM enrolled in a PrEP trial. Presented at the Conference on Retroviruses and Opportunistic Infections, Seattle, WA, 13-16 February, 2017.

Troy Grennan, MD, DTM&H, MSc, FRCPC, Mark Gilbert, MD, MHSc, FRCPC, Mark Hull, MD, FRCPC. A new avenue to explore in STI prevention. BCMJ, Vol. 59, No. 9, November, 2017, Page(s) 480 - 486 - BC Centre for Disease Control.



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