Four years of PrEP use; sexual behaviour and STIs in the AMPrEP demonstration project cohort among men who have sex with men in Amsterdam, the Netherlands

Background An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension about possible risk compensation, particularly on the long term. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. Methods The Amsterdam PrEP demonstration project (AMPrEP) provided oral daily PrEP and event-driven PrEP to MSM and transgender women in 2015-2020. Participants could choose their PrEP regimen, and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in number of sex partners and condomless anal sex acts over time with casual partners (CAS) using negative binomial regression. We assessed changes in incidence rates (IR) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis), individual STIs, and HIV over time using Poisson regression. Findings 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (IQR=3.4-4.0). The number of sex partners decreased over time (adjusted rate ratio [aRR]=0.89/year, 95%CI=0.86-0.92), while the number of CAS acts with casual partners remained stable (aRR=0.98/year, 95%CI=0.94-1.01). IR of any STI was 87/100 person years (PY) (95%CI=82-93) and did not change over time for both daily PrEP or event-driven PrEP users. However, IRs of chlamydia and gonorrhoea decreased slightly in daily PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Interpretation With no increase in the number of casual sex partners nor of CAS acts, we found no indication of possible risk compensation during the first four years of PrEP use. Although the STI incidence was high, it did not increase over time. Funding ZonMw, RIVM, GGD, H-TEAM, Gilead. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: PA has received personal fees from Gilead, Merck, Viiv, and research support from Gilead, paid to his institution. ### Clinical Trial the Netherlands Trial Register (NL5413) ### Funding Statement The authors received no specific funding for this work. The AMPrEP study received funding as part of the H-TEAM initiative from ZonMw (grant number: 522002003), the National Institute for Public Health and the Environment (RIVM), GGD research funds and the H-TEAM. The study drug and an unrestricted research grant for AMPrEP was provided by Gilead Sciences. The H-TEAM initiative is supported by the Aidsfonds Netherlands (grant number: 2013169), Stichting Amsterdam-Dinner Foundation, Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CONL-276-4222,CO-US-276-1712), Janssen Pharmaceuticals (reference number: PHNL/JAN/0714/0005b/1912fde), M.A.C. AIDS Fund and ViiV Healthcare (PO numbers: 3000268822, 3000747780). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics board of the Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands (NL49504.018.14). Participants gave written informed consent to participate in the study before taking part. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available upon reasonable request. The AMPrEP data are owned by the Public Health Service of Amsterdam. Original data can be requested by submitting a study proposal to the steering committee of AMPrEP. The proposal format can be obtained from amprep@ggd.amsterdam.nl. Request for further information can also be submitted through the same email address. The AMPrEP steering committee verifies each proposal for compatibility with general objectives, ethical approval and informed consent forms of the AMPrEP study and potential overlap with ongoing studies. There are no restrictions to obtaining the data and all data requests will be processed in a similar way.