Research highlights an increase in informal use of doxyPEP/PrEP among key populations in the Netherlands

New research analyzing an online survey of 1,633 respondents found 15% recent use of doxycycline post- and pre-exposure prophylaxis (doxyPEP/PrEP) among men who have sex with men (MSM), transgender and gender diverse people in the Netherlands according to a recent study published by Eurosurveillance. These data highlight an increase in the informal use of doxyPEP/PrEP, with 65% of the participants intending to use it in the future. Currently, doxyPEP/PrEP is not recommended or actively promoted by healthcare professionals in the Netherlands. Informal use i.e. without a prescription by a healthcare professional, could contribute to antimicrobial resistance (AMR) and changes in the microbiome.

The use of doxyPEP has been shown to be an effective method in the prevention against sexually transmitted infections (STIs) in MSM, transgender and gender diverse persons. Clinical trials of doxyPEP have shown significant reductions in syphilis and chlamydia, with additional potential to reduce incidence of other bacterial STIs such as chlamydia and gonorrhea

However, the public health implications of the widespread use of doxyPEP are subject to current debate. The administration of doxyPEP to specific individuals could prevent a substantial number of STIs and lower antibiotic use, particularly among those who repeatedly have STIs.

Informal doxyPEP/PrEP use associated with HIV PrEP use, sexualized drug use and perception of safety

As highlighted by this paper and an accompanying editorial by Lyons et al., the prescription of doxyPEP to many sexually active individuals poses the risk of a substantial population-level increase in overall antibiotic consumption and an increase in AMR.

Teker et al. reviewed data from a cross-sectional study gathered from an online survey among MSM, transgender and gender diverse persons of 18 years of age or older. The survey focused on previous use of doxyPEP or doxyPrEP awareness and intention to use it. Participants were recruited through advertisements at the Centre for Sexual Health in Amsterdam, the Netherlands, as well as dating apps (Grindr), Instagram, Facebook, Facebook Messenger and targeted Instagram accounts.

In the study, 23% of participants reported having ever used doxyPEP/PrEP and 15% reported having used doxyPEP/PrEP in the six months prior to the survey. Respondents informing about recent use were more likely to report living with HIV or frequently using oral HIV PrEP in the six months before taking the survey. They were also more likely to report a history of bacterial STIs, having a higher number of sexual partners, and a higher frequency of engaging in chemsex and in group sex during that period.

Doxycycline was the most used antibiotic reported in this study, with 46% of the participants reporting using it recently as PEP, 29% of recent PEP users using it as PrEP and 25% using it as a combination of both. 

Overall, the intention to use doxyPEP/PrEP was very high among the study population, with more than half of the participants (65%) expressing intention to use. More than two thirds of respondents (72%) were willing to pay for doxyPEP/PrEP if it became formally available, indicating a potential demand for the drug among the study population and beyond. 

It was also found that doxyPEP/PrEP was primarily obtained from countries outside of the Netherlands or through prescriptions, with participants paying on average €30 for the drug.

Additional determinants for both informal use of doxyPEP/PrEP and high intention to use included using oral HIV PrEP or living with HIV, receiving advice from others to use doxyPEP/PrEP and perceiving doxyPEP/PrEP as an effective and safe method of STI prevention.

Potential antimicrobial resistance risks from lack of monitoring

The impact of prophylactic antibiotic use on AMR was highlighted in the study as there are uncertainties regarding the long-term adverse effects of doxyPEP/PrEP use. Teker et al. emphasize the potential harms of doxycycline effectiveness and AMR risks, as summarised in previous studies including in the United States. 

They also cite its potential effects on the gut microbiome, which need to be studied further. If doxyPEP is implemented in country-wide clinical guidance, it would be vital to monitor both individual and population-level resistance to doxycycline.

Lack of awareness on the extent of informal use of doxyPEP/PrEP makes it difficult to monitor and implement appropriate public health stewardship. This leads to difficulties in detecting overuse, misuse and adverse effects including AMR development and effects on microbiome composition.