Doxycycline for sexually transmitted infections' prevention: Balancing promise and public health concerns

Abstract

The continuing rise in the incidence of sexually transmitted infections (STIs) poses a significant public health challenge and necessitates novel prevention strategies to curb their spread. One such strategy could be the use of doxycycline as both pre-exposure (Doxy-PrEP) and post-exposure prophylaxis (Doxy-PEP).

The review by Stratman and Zampella¹ in the present issue explores the potential of Doxy-PrEP and Doxy-PEP against bacterial STIs. Concerning Doxy-Prep, there is only limited evidence from two studies in small groups of men who have sex with men (MSM) and transgender women, with mixed outcomes. Doxy-PEP has been assessed in three trials among MSM that revealed promising efficacy in reducing the incidence of syphilis and chlamydia, while the effect on gonorrhea was more modest. For example, the DOXYVAC study reported an 83.5% reduction in chlamydia and syphilis and a 33.5% drop in gonorrhea among MSM utilizing Doxy-PEP, suggesting that targeted interventions could be effective in high-risk populations.² However, the efficacy of Doxy-PEP among other populations, such as cisgender women, remains unclear, as evidenced by a study in Kenya that found no significant benefits in this population.³ Nonadherence as well as biologic differences could be explored as potential explanations for this lack of efficacy, raising concerns about the generalizability of Doxy-PEP beyond MSM.

A critical concern about the broad use of Doxy-PEP emphasized by Stratman and Zampella¹ is the facilitation of antimicrobial resistance, especially for Neisseria gonorrhoeae strains. Increased antibiotic exposure could accelerate selective pressure on bacterial populations, affecting not only STI-causing pathogens but also other common bacterial pathogens (e.g. Staphylococcus aureus) and commensal flora, leading to broader antimicrobial resistance concerns.⁴ These risks underscore the need for cautious implementation and robust surveillance mechanisms to assess resistance patterns and inform clinical guidelines.

In addition to scientific and clinical challenges, integrating Doxy-PEP into public health programmes presents logistical and ethical dilemmas, particularly in determining standardized protocols for patient selection, adherence monitoring, and resistance tracking. Current recommendations from the European branch of the International Union of Sexually Transmitted Infections (IUSTI)⁵ and other health organizations advocate for a shared decision-making approach in prescribing Doxy-PEP to MSM and transgender women at high risk, yet there is no consensus on universal guidelines, raising questions about equitable access and resource allocation in lower-income settings where STIs prevention measures are already insufficient. Ethical concerns surrounding Doxy-PEP access further complicate its implementation, particularly regarding disparities in healthcare availability and affordability, as some high-risk populations may lack adequate access to STI prevention tools due to structural inequities.

To ensure responsible implementation of Doxy-PEP, further research is needed to answer key questions: How effective is Doxy-PEP in other high-risk populations, including cisgender women and heterosexual men? What are the long-term consequences of increased doxycycline use on bacterial resistance patterns? How can public health systems integrate Doxy-PEP into existing STI prevention frameworks without exacerbating antimicrobial resistance? What strategies can ensure equitable access to Doxy-PEP for those who would benefit most?

Doxy-PEP is a promising intervention for reducing bacterial STIs in high-risk populations, particularly MSM. However, as emphasized by IUSTI Europe⁵ and the review by Stratman and Zampella,¹ issues regarding antimicrobial resistance, population-wide impact, and implementation logistics must be carefully considered. Policymakers and healthcare providers must balance the benefits and risks to develop sustainable, evidence-based STI prevention strategies. Ongoing research and surveillance will be essential to refining guidelines and ensuring that Doxy-PEP remains a viable option without contributing to the growing threat of antibiotic resistance.

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None declared.

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