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Doxycycline post-exposure prophylaxis among men who have sex with men and transgender women in Belgium: awareness, use and antimicrobial resistance concerns in a cross-sectional online survey
  1. Thibaut Vanbaelen1,
  2. Anke Rotsaert2,
  3. Irith De Baetselier1,
  4. Tom Platteau1,
  5. Bernadette Hensen2,
  6. Thijs Reyniers2,
  7. Chris Kenyon1
  1. 1 Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
  2. 2 Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
  1. Correspondence to Dr Thibaut Vanbaelen, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, 2000, Belgium; tvanbaelen{at}itg.be

Abstract

Objectives We aimed to assess the awareness, willingness to use and use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR).

Methods Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organisations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ2 or Fisher’s exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR.

Results 875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32–48), 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the previous 6 months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with reporting ≥1 sexually transmitted infection (STI) in the previous 12 months, engagement in chemsex, HIV status and pre-exposure prophylaxis use, and education level.

About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use decreased to 60% and concerns of side effects/AMR increased to around 70%.

Conclusions Approximately 1 in 10 MSM in Belgium reported using doxyPEP. A recent history of STIs and STI risk factors were positively associated with doxyPEP use. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.

  • Gonorrhea
  • Chlamydia Infections
  • SYPHILIS
  • Antibiotic Prophylaxis
  • Post-Exposure Prophylaxis

Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request and according to ITM data sharing policy.

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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Several randomised controlled trials have shown the efficacy of doxycycline postexposure prophylaxis (doxyPEP) on the incidence of chlamydia, syphilis and in some instances, gonorrhoea, among men who have sex with men (MSM) and transgender women (TGW). However, the potential for antimicrobial resistance (AMR) due to increased doxycycline consumption is a major concern, leading to some guidelines not recommending doxyPEP. Informal use of doxyPEP has been reported by up to 10% of MSM in countries where it is not recommended.

WHAT THIS STUDY ADDS

  • We found that about 1 in 10 MSM in Belgium has ever used doxyPEP, with a majority having used it in the previous 6 months. DoxyPEP use was associated with reporting one or more sexually transmitted infection (STIs) in the preceding year, having engaged in chemsex in the previous 6 months, living with HIV or taking pre-exposure prophylaxis, and education level. The willingness to use doxyPEP was high but decreased after presenting information about the potential effects of doxyPEP on AMR. In contrast, concerns regarding doxyPEP side effects were high and further increased after presenting information about the potential effects of doxyPEP on AMR.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • By highlighting the prevalence and factors associated with informal doxyPEP use, this study can inform future research directions, guiding further investigations into patterns of STI prevention among MSM and TGW in Belgium. The insights the study adds of the impact of AMR concerns on the willingness to use doxyPEP can influence clinical practice by emphasising the importance of comprehensive patient education to ensure informed decision-making regarding STI prevention strategies. From a policy perspective, the study underscores the need for a comprehensive assessment of the challenges and benefits of doxyPEP, balancing its potential for reducing STI incidence with the risks of promoting AMR.

Introduction

Three randomised controlled trials (RCTs) have demonstrated the efficacy of doxycycline postexposure prophylaxis (doxyPEP) in reducing the incidence of bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM).1–3 In these RCTs, doxyPEP reduced the incidence of Chlamydia trachomatis by 70%–88% and syphilis by 73%–87%.1 2 The efficacy of doxyPEP on the incidence of Neisseria gonorrhoeae (NG) is less clear, with some studies demonstrating a reduction in NG cases, whereas others found no effect on incidence.2 4 The main concerns related to doxyPEP use are that it could induce resistance to tetracyclines and other antimicrobials in NG and other bacteria and could lead to deleterious alterations in the resistome and microbiome.5 For these reasons, while some guidelines promote the use of doxyPEP in MSM, others advised against it.6 7

There are reports of informal use of antibiotics for STI prevention in countries where doxyPEP is not currently recommended. For instance, in 2020, it has been shown that 2%–10% of MSM reported using doxyPEP in the Netherlands, the United Kingdom (UK) and Australia.8–10 In Belgium, we found that about 3.2% of HIV pre-exposure prophylaxis (PrEP) users reported having ever taken antibiotics preventatively for bacterial STIs in 2022.11 While the use seemed rather limited, the awareness of such practices was high, with about one-third of PrEP users having heard of doxyPEP and one-tenth knowing someone who currently used doxyPEP.11 DoxyPEP has also gained a lot of attention in the past year, following the publication of the results of several doxyPEP RCTs and its roll-out in San Francisco.12 We, therefore, hypothesised that the awareness and use of doxyPEP in Belgium have increased since 2022.

We aimed to assess the awareness, willingness to use and use of doxyPEP among MSM and transgender women (TGW) in Belgium in 2024. Moreover, we aimed to assess sociodemographic factors and sexual behaviours associated with doxyPEP use and concerns regarding the effect of doxyPEP on antimicrobial resistance (AMR).

Methods

Study design and participants

We conducted a cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications (Grindr, Recon, Scruff, Jack’d) and social media platforms of community-based organisations. Potential participants were informed about the study and provided consent by agreeing to participate. Inclusion criteria were being 18 years old or older; assigned male sex at birth; identify as MSM or as a TGW; living in Belgium; had sex with at least one non-steady partner in the previous 12 months; being able to read and understand Dutch, French or English and willing and be able to provide informed consent. After eligibility check, eligible participants were invited to start the questionnaire.

The questionnaire was pilot tested by research team members and available in Dutch, French or English. It included questions on sociodemographic characteristics (eg, age, region of residence, highest level of education attained), awareness, willingness to use, current and past use of doxyPEP, sexual behaviours (eg, engagement in chemsex, number of non-steady sexual partners and condom), HIV status and PrEP use, and history of STI diagnoses (online supplemental appendix 1). Responses were collected anonymously, and participants were allowed to skip questions. Hence, the denominator of the collected answers may vary.

Supplemental material

In the questionnaire, we first presented a short text describing doxyPEP and assessed awareness of doxyPEP using the questions ‘before today, had you ever heard of doxyPEP as a way to prevent bacterial STIs?” with the response options ‘yes’ or ‘no’. Subsequent doxyPEP use questions were only asked to participants who had ever heard of doxyPEP, these included: ‘have you ever used or are you currently using doxyPEP?’. Response options were: ‘Yes, I am using it now’, ‘Yes, I have used it but not anymore’ and ‘No’. Subsequent questions about how doxyPEP was used were only asked to participants who reported current or past doxyPEP use.

Willingness to use doxyPEP and concerns of its side effects were explored among all respondents, whether or not they had heard of doxyPEP. Willingness to use doxyPEP was assessed with the question ‘would you be willing to use doxyPEP to limit the risk of getting an STI?’ with ‘certainly not’, ‘probably not’, ‘undecided’, ‘probably yes’ and ‘certainly’ as response options. Concerns regarding doxyPEP side effects were assessed by the question ‘with your current knowledge, how unconcerned or concerned are you about potential short-term and long-term side effects of doxyPEP?’ with ‘not concerned at all’, ‘rather not concerned’, ‘nor concerned nor unconcerned’, ‘rather concerned’ and ‘very concerned’ as possible response options. Subsequently, we presented a short paragraph describing the potential effects of doxyPEP on AMR and assessed concerns of AMR with the question ‘with this additional information in mind, how unconcerned or concerned are you about doxyPEP leading to the emergence of AMR in STI?’ with the same possible response options as for the previous question. Finally, we reassessed the willingness to use doxyPEP using the same question as before.

Data analysis

We described numerical variables using medians and IQRs, and categorical variables using absolute numbers and proportions. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ2 test or Fisher’s exact test. Willingness to use doxyPEP and concerns of side effects/AMR before and after the short paragraph about AMR were compared with McNemar-Bowker test.

We explored whether sociodemographic characteristics and sexual behaviours were associated with doxyPEP use using logistic regression analyses. For this purpose, the variable doxyPEP use was dichotomised into participants who never took doxyPEP and participants reporting current or past doxyPEP use. We first performed univariable logistic regression to select the variables to include in a multivariable logistic regression analysis. Variables associated with doxyPEP use at the p≤0.10 level were included in a multivariable regression model. The final multivariable model was built by backward selection, using the likelihood ratio test and a significance level set at 0.05. The multivariable regression model was adjusted for age and HIV status and PrEP use.

All computations were performed using R studio V.4.2.0.13

The Strengthening the Reporting of Observational Studies in Epidemiology checklist for reporting cross-sectional studies is found in online supplemental appendix 2.

Supplemental material

Results

Survey participation and sociodemographic characteristics

A total of 1131 individuals accessed the survey between 9 April and 30 April 2024 and 948 (83.8%) agreed to participate. Among them, 73 did not meet the inclusion criteria and 875 started the survey. The median age of participants was 40 years (IQR 32–48, table 1). Almost all participants identified as men (860/875, 98.3%), 1 identified as transgender women (1/875, 0.1%), 12 as non-binary (12/875, 1.4%), 1 as queer (1/875, 0.1%) and 1 as bisexual-gay (1/875, 0.1%). Most participants were born in Belgium (632/875, 72.2%), had completed or were completing short-type or long-type higher education (725/875, 82.9%), had social security (838/875, 95.8%) and half lived in Flanders (501/875, 57.3%).

Table 1

Factors associated with doxyPEP use in a univariable and multivariable logistic regression analysis

Sexual behaviour, HIV status and history of STIs

Eighty-six participants (86/845, 10.2%) were living with HIV, two-thirds (519/845, 61.4%) were taking PrEP, and 240 were HIV negative or had an unknown HIV status and were not taking PrEP (240/845, 28.4%; table 1). About half the participants reported an STI in the previous year (395/843, 46.9%), and 119 had more than two STIs in the previous year (119/843, 14.1%). The most frequently reported STIs were gonorrhoea (242/844, 28.7%), chlamydia (222/844, 26.3%), followed by syphilis (118/844, 14.0%). The median self-perceived STI risk was 7 (IQR 5–8) on a scale of 0–10 (0 representing very low risk and 10 very high risk). Most participants were rather or very concerned about acquiring STIs (575/841, 68.4%) and found it rather or very important to protect themselves or their partners against STIs (751/837, 89.7% and 770/836, 92.1%, respectively). Around one-third of participants reported having engaged in chemsex in the previous 6 months (258/836, 30.9%).

DoxyPEP awareness and use

About 40% of the participants had ever heard of doxyPEP as a way to prevent bacterial STIs (352/875, 40.2%, table 2). Of these, around half had heard of it through community organisations (186/350, 53.1%). Interestingly, nine participants (9/350, 2.6%) mentioned in free text that they had heard about doxyPEP via international friends or organisations. About 10% of all participants had ever used doxyPEP (82/875, 9.4%). Among those, almost all took 200 mg of doxycycline after sex (70/81, 86.4%), the majority had used it last in the previous 6 months (70/81, 86.4%) and used it less than monthly (51/81, 63%). DoxyPEP was mostly used when having group sex (60/80, 75%), when having sex with an anonymous partner (59/80, 73.8%) or when engaging in chemsex (33/80, 41.3%). DoxyPEP was used more frequently for receptive or insertive anal sex without a condom (62/80, 77.6% and 58/80, 72.5%, respectively) than for receptive or insertive oral sex without a condom (39/80, 48.8% and 43/80, 53.8%, respectively). The main sources of doxyPEP were leftover antibiotics (30/80, 37.5%) and getting doxycycline from friends or sex partners (23/80, 28.8%).

Table 2

DoxyPEP awareness and use

Factors associated with doxyPEP use

In univariable logistic regression analyses, current or past doxyPEP users were more likely to reside in Brussels or in Flanders than in Wallonia (OR 3.38 (95% CI 1.49 to 9.10) and OR 1.35 (95% CI 0.59 to 3.64), respectively). They were also more likely to have completed or be in higher education compared with having no higher education (OR 1.77 (95% CI 0.94 to 3.64)), and to be living with HIV or taking PrEP compared with being HIV negative or unknown HIV status and not taking PrEP (OR 5.39 (95% CI 2.09 to 14.98) and OR 4.43 (95% CI 2.13 to 10.78), respectively). DoxyPEP use was associated with reporting 1–2 or >2 STIs in the previous year (OR 3.72 (95% CI 2.13 to 6.70) and OR 5.12 (95% CI 2.67 to 9.92), respectively, self-perceived a higher STI risk (OR 1.24 (95%CI 1.10 to 1.42)), having had a higher number of non-steady partners for anal sex in the previous 6 months (OR 1.002 (95% CI 1 to 1.005)) and having engaged in chemsex in the previous 6 months (OR 2.92 (95% CI 1.83 to 4.68)).

In the multivariable regression analysis, doxyPEP use remained significantly associated with reporting 1–2 or >2 STIs in the previous 12 months (aOR 2.49 (95% CI 1.36 to 4.58) and aOR 3.24 (95% CI 1.59 to 6.57), respectively), engagement in chemsex in the previous 6 months (aOR 2.25 (95% CI 1.35 to 3.75)), living with HIV or taking PrEP (aOR 2.93 (95% CI 1.01 to 8.49) and aOR 2.41 (95% CI 1.03 to 5.60), respectively), and education level, while adjusting for age.

Willingness to use doxyPEP and concerns of side-effects and AMR

About 80% of the participants initially reported being certainly or probably willing to use doxyPEP (387/868, 44.6% and 331/868, 38.1%, respectively, figure 1) and about 7% were probably or certainly not willing to use it (50/868, 5.8% and 7/868, 0.8%, respectively). After reading a paragraph describing the potential effects of doxyPEP on AMR, the proportion of those being certainly or probably willing to use doxyPEP declined to about 60% (193/859, 22.5% and 327/859, 38.1%, respectively) and the proportion of those probably or certainly not willing to use it increased to about 18% (125/859, 14.6% and 31/859, 3.6%, respectively). This change was statistically significant (p<0.001).

Figure 1

Willingness to use doxyPEP (above panel) and concerns of side effects and AMR (below panel). AMR, antimicrobial resistance; doxyPEP, doxycycline postexposure prophylaxis.

About half of the participants initially reported being very or rather concerned about potential short-term and long-term side effects of doxyPEP (58/859, 6.7% and 371/859, 42.7%, respectively, figure 1), and about a quarter were rather not or not at all concerned (135/859, 15.6%, and 55/859, 6.4%, respectively). After reading the short AMR paragraph, more than two-thirds of the participants were rather or very concerned about the potential for doxyPEP leading to AMR (178/859, 20.7% and 417/859, 48.5%, respectively), and about one in ten were rather not or not at all concerned (82/859, 9.5%, and 22/859, 2.6%, respectively).

Discussion

We found that about one in ten MSM in Belgium has ever used doxyPEP, with a majority of these individuals having used it in the prior 6 months. DoxyPEP use was associated with reporting STIs in the preceding year, living with HIV or taking PrEP, and having engaged in chemsex in the preceding 6 months. Willingness to use doxyPEP was high but decreased after presenting information about the potential effects of doxyPEP on AMR while concerns of doxyPEP side effects increased after presenting information about the potential effects of doxyPEP on AMR.

Our finding that approximately 10% of MSM in Belgium have used doxyPEP is consistent with previous studies. Surveys in the UK and Australia found that 9% and 10% of PrEP users were already using doxyPEP, respectively, despite not being formally recommended at the time.10 14 In Belgium in 2022, we found that 3.2% of PrEP users were using antibiotics for STI prevention and 28.9% had heard of it.11 These proportions seem to have increased, although careful consideration should be taken when comparing studies with different sampling methodologies, timeframes and study populations. The publication of doxyPEP RCT results and its implementation in San Francisco may have increased awareness and informal use among MSM. Some participants in our study reported learning about doxyPEP through international friends or organisations, supporting this hypothesis. Furthermore, other European countries recently reported similar levels of informal doxyPEP use.15

Consistent with previous studies, we found that doxyPEP use was associated with engagement in chemsex, PrEP use and recent STIs.10 16 17 It has been shown that chemsex and PrEP use are associated with higher rates of STIs.18 19 Our findings suggest that those who are the most at risk for STIs are the ones reporting doxyPEP use. Moreover, among doxyPEP users, the main circumstances of use were high-risk events for STIs like group sex or sex under the influence of substances. While it might seem appropriate that those who are the most at risk for STIs are the ones using doxyPEP, careful consideration should be taken to high antimicrobial consumption in this population. Previous studies have shown that AMR has frequently emerged in core groups with high antimicrobial consumption, before spreading to other populations.20 We, and others, have previously shown that rolling out doxyPEP would lead to a substantial increase in doxycycline consumption, leading to a risk of selecting or inducing AMR in a wide range of pathogens, including NG.21–25 While doxyPEP may have the largest STI incidence impact in high-risk groups, it may also have the greatest AMR effect in this group.

After providing information about the potential risks of AMR associated with doxyPEP, willingness to use doxyPEP decreased and the concerns of side effects/AMR increased. Previous qualitative studies reported high willingness to use doxyPEP despite up to 50% of participants voicing AMR concerns.26 27 In these studies, participants reported that more information about the potential side effects of doxyPEP, including AMR, is necessary before deciding on doxyPEP use. Our study is the first to assess how providing AMR information can influence the willingness to use doxyPEP. These insights underscore the importance of informing potential users about both the benefits and harms of doxyPEP to enable informed decisions about use.

Our study has several limitations. First, the study was advertised on a limited number of sexual networking applications and social media platforms. Moreover, potential self-selection is inherent to the online study design. Hence, the sample may not be representative of the entire MSM population in Belgium. Our survey was advertised as a doxyPEP survey, which might have led to individuals who knew doxyPEP being overrepresented in our sample. Second, participants’ responses might be affected by a recall bias and, given the sensitive and nature of the questions, subjects might be prone to social desirability bias, which could have led to under-reporting of sexual risk-taking. Finally, since doxyPEP is currently not recommended in Belgium, participants may have been less willing to report informal use.

In conclusion, informal doxyPEP use appears to be increasing among MSM in Belgium, with those at highest STI risk reporting more use. While targeting doxyPEP to those at highest risk for STIs may seem appropriate, high antimicrobial consumption in this population raises AMR concerns. Importantly, AMR and side effect concerns could influence willingness to use doxyPEP. If doxyPEP is introduced, informing patients about the benefits and risks of doxyPEP will be crucial to enable informed decision-making.

Abstract translation

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request and according to ITM data sharing policy.

Ethics statements

Patient consent for publication

Ethics approval

We obtained ethical approval from the Institutional Review Board of the Institute of Tropical Medicine (IRB 1753/24). Participants gave informed consent to participate in the study before taking part.

References

Footnotes

  • Handling editor Stefano Rusconi

  • Contributors TV (guarantor): conceptualisation, methodology, investigation, formal analysis, writing—original draft, visualisation, project administration, funding acquisition; AR: conceptualisation, methodology, writing—review and editing; IDB: conceptualisation, methodology, writing—review and editing; TP: conceptualisation, methodology, writing—review and editing; BH: conceptualisation, methodology, writing—review and editing; TR: conceptualisation, methodology; CK: conceptualisation, methodology, writing—review and editing, supervision.

  • Funding This study was funded by a research grant from Viatris (BEL3882). Viatris played no role in the study design, collection or interpretation of the study results.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer-reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.