Recurrence of sexually transmitted infections is commonly found in a subpopulation of Austrian users of HIV pre-exposure prophylaxis

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) has emerged as a highly effective and safe HIV prevention strategy [1, 2]; however, its implementation has been accompanied by frequent screening for sexually transmitted infections (STIs), such as gonorrhea, chlamydia and syphilis [3], causing a rise in STI incidence [4]. Men who have sex with men (MSM) are the primary target group for PrEP services in countries like Austria and Germany [5] as, compared to the general population, they are more likely to engage in condomless anal intercourse (CAI) with casual partners [6] as well as in sexualized drug use (chemsex). Chemsex has experienced a growing prevalence in many western countries [7, 8], involves the use of recreational drugs like mephedrone or gamma-hydroxybutyric acid to enhance sexual experiences and has been linked to transmission-prone sex practices like CAI. Furthermore, chemsex is associated with a higher STI prevalence [9, 10]. In Austria, PrEP became widely accessible in 2018 [11]; however, despite a substantial number of individuals meeting PrEP eligibility criteria, its rollout has been hampered by limited PrEP service availability and delayed coverage by the healthcare providers [12]. Comprehensive data regarding characteristics, sexual risk behavior and STI prevalence and incidence among PrEP users in Austria have been scarce. This study aimed to address these gaps by investigating Austrian PrEP users longitudinally. These findings can inform PrEP services and healthcare authorities on current challenges in Austrian PrEP users and serve as a baseline for the upcoming era of doxycycline postexposure prophylaxis (Doxy PEP).

In this prospective observational cohort study, 360 PrEP users were included with 263 being followed over 379 person-years. A high incidence of mostly asymptomatic STIs among PrEP users was found and chemsex users were disproportionately affected. Furthermore, study participants frequently engaged in transmission-prone sex practices, including chemsex and CAI. Ultimately, chemsex was identified as a predictor for STI reinfection among PrEP users.

In our cohort, STI incidence rates were relatively high, with gonorrhea at 29.8, chlamydia at 22.7, and syphilis at 9.8 per 100 person-years. These findings emphasize the substantial risk of bacterial STIs among PrEP users despite effective HIV prevention. Our findings are supported by other studies on PrEP users. For example, in a meta-analysis Werner et al. reported pooled incidence estimates of gonorrhea, chlamydia, and syphilis at 39.6, 41.8, and 9.1 per 100 person-years, respectively [13]. Comparable results were found in cohort studies from Australia [4] and the Netherlands [14], underlining the high burden of bacterial STIs in this population. Additionally, we identified a new HIV infection in our cohort of PrEP users, which occurred in an individual with inconsistent adherence to PrEP. This is one more unfortunate example that the effectiveness of oral PrEP is mainly limited by adherence and not the regimen’s efficacy. Accordingly, PrEP users should receive frequent counselling on the importance of consistent PrEP use.

In our cohort, 44% of participants reported chemsex use. This is in line with findings from Hoornenborg et al., who reported a chemsex prevalence of 41% in the AMPrEP study in the Netherlands [15], and Anato et al., who found a prevalence of 24% among PrEP users [16]. A higher prevalence of 63% was reported in a study from Barcelona [17]; however, differences in chemsex prevalence may be associated with varying definitions of the term. The Barcelona study included the use of nitrites and erectile dysfunction drugs in its definition of chemsex; typically, only recreational drugs are considered for defining chemsex [15, 16].

Chemsex has consistently been associated with increased CAI incidence [10, 14] and diagnoses of bacterial STIs [10, 16]. The impact of chemsex on STI risk emerged as a critical finding in our research. Participants engaging in chemsex not only exhibited higher rates of STIs but also were more likely to experience reinfections. Moreover, urethral and anal gonococcal infections were found significantly more often in individuals engaging in chemsex practices, potentially facilitated by prolonged and more traumatic sexual activities during chemsex. Additionally, MSM involved in chemsex have been reported to have a greater number of sexual partners and to be more likely to engage in group sex compared to those who do not engage in chemsex practices [18].

Importantly, we found that only a minority, 18% of individuals with 1 or more reinfections, accounted for 68% of all detected STIs. Similar findings were reported by Traeger et al. [4], where 25% of participants accounted for 76% of diagnosed STIs. This indicates that a small group of individuals experienced the majority of STIs, suggesting an opportunity for targeted prevention strategies. We hypothesize that these individuals at highest STI exposure could benefit from more frequent screening. They may also benefit from Doxy PEP, a postexposure prophylaxis containing doxycycline taken within 24–72 h after CAI. The use of Doxy PEP has been shown to significantly decrease the incidence of chlamydia and syphilis infections [19].

In our analysis, most STIs were asymptomatic, yet antimicrobial treatment was initiated following each positive result, in line with current STI treatment guidelines [20]. A low number of symptomatic infections at extragenital sites is commonly observed. In our study, only one in four individuals with anal gonorrhea or chlamydia reported symptoms, which aligns with previously reported numbers ranging from 15–25% [21, 22]. Interestingly, we observed an asymptomatic course of disease in 44% of urethral gonorrhea. Conventionally, symptoms of urethral N. gonorrhoeae infections in men are expected in more than 90% of cases [23]. Notably, previous studies predominantly focused on testing individuals with symptomatic urethritis and not on screening. It can be expected that an upscaling of screening for infections will also increase the proportion of asymptomatic infections detected. In this context, the frequency of screening for N. gonorrhoeae and C. trachomatis as well as the necessity for treatment and associated harm have recently sparked debate. Williams et al. discussed the potential benefits of reducing the screening frequency for gonococcal and chlamydial infections to every 6 or 12 months, while maintaining quarterly screenings for HIV and syphilis, given their higher risk of complications when undiagnosed. Their analysis suggested potential advantages of this approach, including reduced antibiotic exposure, fewer individual adverse effects (such as microbiome disruption or Clostridium difficile infection), decreased antimicrobial resistance due to lower antibiotic use at a population level, and cost and resource savings for healthcare systems [24]; however, reducing the screening frequency might have potential drawbacks, including unknown risks of long-term asymptomatic infections by gonorrhea and chlamydia and the potential to transmit these pathogens to women, in whom these infections may potentially cause complications like pelvic inflammatory disease or infertility. The authors concluded that a reduction in screening frequency for chlamydia and gonorrhea would be favorable overall, a conclusion also supported by Kenyon et al. in a recent comprehensive review [25].

While modeling studies have suggested that frequent STI screening might reduce incidence rates [26‐28], empirical studies on chlamydia and gonorrhea prevalence have failed to meet these predictions [29, 30]. For instance, the Gonoscreen study, a randomized, controlled trial enrolling two groups of approximately 500 MSM using PrEP, compared the effects of quarterly screening vs. no screening on STI incidence. The authors described a significant reduction in chlamydia infections with screening, while gonorrhea rates remained unchanged; however, the authors discussed that the increased chlamydia incidence in the no screening group was attributed to persistent infections rather than novel infections. In a secondary analysis, correcting for chlamydia positivity at consecutive visits, incidence rates in both groups were comparable [30]. During our observational period, the STI incidence remained stable although individuals were frequently screened. Given the relatively short follow-up period of our study, with 263 participants representing 379 person-years of observation, we cannot draw any conclusions regarding the impact of STI screening on incidence rates.

As strengths of our study, we want to highlight the prospective observational setting and consecutive follow-up, the quarterly STI screening and the detailed information on chemsex use. Importantly, our research provides the very first insights into STI incidence among PrEP users in Austria; however, the study has limitations, including its single-center design, potential bias in self-reported data and a possible selection bias, as it was conducted at a tertiary care hospital.

In conclusion, our study reports on the high incidence of bacterial STIs among PrEP users in Austria, particularly among those involved in chemsex. The absence of new HIV infections demonstrates the effectiveness of PrEP. The recent decision by Austrian healthcare providers to reimburse PrEP [12] marks a significant step towards improving access to HIV prevention. Continued efforts should focus on including regular HIV and syphilis screening in PrEP users. The high number of asymptomatic infections in our study suggests a need to rethink current diagnostic and therapeutic strategies. These measures not only support the overall well-being of PrEP users but also help reduce HIV transmission rates and the overuse of antimicrobial treatment, potentially mitigating the development of antimicrobial resistance.