Offering a choice of daily and event-driven preexposure prophylaxis for men who have sex with men in the Netherlands: a cost-effectiveness analysis : AIDS

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Offering a choice of daily and event-driven preexposure prophylaxis for men who have sex with men in the Netherlands: a cost-effectiveness analysis

van Hoek, Albert Jana; Reitsema, Maartena,b; Xiridou, Mariaa; van Sighem, Ardc; van Benthem, Birgita; Wallinga, Jaccoa,b; van Duijnhoven, Yvonned; van der Loeff, Maarten Schimd,e; Prins, Mariad,e; Hoornenborg, Elsked,f

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AIDS 35(10):p 1677-1682, August 1, 2021. | DOI: 10.1097/QAD.0000000000002913



Men who have sex with men (MSM) accounted for approximately 66% of 664 new HIV diagnoses in the Netherlands in 2018 [1]. Daily and event-driven preexposure prophylaxis (PrEP) have been shown to have similar high efficacy in protecting against HIV acquisition [2,3]. Event-driven PrEP provides choice and convenience, reduces pill burden and costs, and can be an alternative for MSM who do not want or need daily medication [4,5]. Demonstration studies found that, if given a choice, MSM often switch between daily and event-driven PrEP [6,7]. Recommendations from the World Health Organization were extended with event-driven PrEP in 2019 [8]. Evaluations of PrEP uptake and accessibility, but also of cost-effectiveness and budgetary impact are crucial for public health policy decisions about the implementation of PrEP programmes. To provide input for policy making, we assessed the cost-effectiveness of a PrEP programme offering a choice of daily and event-driven PrEP and of a programme offering daily PrEP only.


Amsterdam Preexposure Prophylaxis Project

In our model, we used data on PrEP use from the Amsterdam PrEP (AMPrEP) demonstration project. AMPrEP was started in 2015, focussing on the uptake, acceptability, and usability of daily and event-driven PrEP for HIV-negative MSM or transgender persons who have sex with men [4,6,9]. The project was designed to provide PrEP to 370 individuals for 3 years, at a time that PrEP was otherwise officially unavailable in the Netherlands. Participants could choose between daily or event-driven PrEP and were allowed to switch between PrEP regimens at quarterly visits.

The transmission and the economic model

We used a stochastic agent-based transmission model and an economic model that we have developed earlier to study the impact and cost-effectiveness of HIV prevention measures [10–12]. The transmission model describes infection with HIV or Neisseria gonorrhoeae (NG) via sexual relationships of MSM. The parameters of the transmission model are shown in Tables S1–S3, Supplemental Digital Content, and in our earlier publications [10–12]. NG infections were included because testing for sexually transmitted infections (STI) carried out for PrEP monitoring can not only affect NG transmission, but also has costs and health effects. Model parameters relating to HIV infection and sexual behaviour were obtained from data from the Netherlands [1,13,14]. Model calculations were carried out for the first 10 years (2018–2027) after the first national recommendations for PrEP use [15].

From the transmission model, we calculated numbers of new HIV and NG infections, HIV and NG tests, and MSM receiving antiretroviral treatment. These numbers were used as input in the economic model to calculate the costs of HIV and NG testing and treatment, PrEP monitoring and medication. Values and sources of the parameters of the economic model are shown in Tables S4–S7, Supplemental Digital Content, and in [11–12]. Health effects were expressed in quality-adjusted life-years (QALY). The impact of a PrEP programme for the Dutch MSM population of 200 000 men [16] was evaluated for 2018–2027 using a healthcare payer's perspective. Costs were discounted by 4% and QALYs by 1.5%, in line with Dutch guidelines for cost-effectiveness analyses [17]. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental costs divided by QALYs gained due to PrEP, compared to without PrEP. For the cost-effectiveness of a scenario, we used the threshold of €20 000 per QALY gained [18].

Preexposure prophylaxis programmes

Eligibility criteria for PrEP were modelled according to the Dutch guidelines for PrEP use [15]. We assumed that 75% of eligible MSM actually started PrEP, as some MSM may decline PrEP use [19]. Quarterly monitoring consisted of tests for HIV, chlamydia, gonorrhoea, and hepatitis C infection, and a renal function test. MSM stay on PrEP for a year, at which point the eligibility criteria are again evaluated. If none of the criteria for PrEP is met, PrEP is interrupted; otherwise, it is continued for another year and then again the criteria are evaluated. We modelled a programme offering only daily PrEP and a programme offering a choice between daily and event-driven PrEP, as in the Dutch PrEP pilot [20]. We used a reduction of 86% in the probability to acquire HIV for those on daily or event-driven PrEP, because the two regimens have comparable efficacy [2,3,21]. We assumed similar adherence with the two regimens and, therefore, their impact on HIV incidence and health effects were the same, as has been shown in demonstration projects offering such a choice [6,7]. Also, we assumed that adverse events and other health conditions were similar in both regimens [22]. PrEP monitoring was also the same in both regimens.


We calculated the cost of PrEP medication at €30–50 for 30 pills [23]. The cost of PrEP monitoring was €150–163 per consultation (every 3 months), calculated by itemizing individual tests and applying the reference costs as listed by the Dutch Healthcare Authority [24] (see also Table S7, Supplemental Digital Content, Costs outside the PrEP programme (antiretroviral therapy and monitoring of those in HIV care, HIV testing, gonorrhoea testing and treatment) were obtained from our earlier cost-effectiveness study [11,12].

Probabilistic sensitivity analysis

For the parameters of the transmission model, 100 combinations of values were generated and 20 stochastic realizations of the model were calculated with each parameter combination. The 100 averages of the 20 realizations formed the input for the economic model. For each of them, 1000 iterations were run with the economic model with different combinations of values for the parameters of the economic model, resulting in 100 000 sets of results.


Preexposure prophylaxis medication

Using data from AMPrEP, we calculated the median pill use at 30 (interquartile range, 29–30) pills per month for individuals on daily PrEP and 12 (interquartile range, 5–19) pills per month, for those on event-driven PrEP (Table 1). Switching between daily and event-driven regimens occurred frequently, but the percentage of participants on event-driven PrEP remained around 27% over time since PrEP initiation.

Table 1 - Use of PrEP medication in the Amsterdam PrEP Demonstration Project (AMPrEP).
Months after PrEP starta Use of PrEP medication (number of pills taken in preceding 30 days)b
Daily Event-driven
n Median [IQR] Mean SD n Median [IQR] Mean SD
3 254 30 [30–30] 28.5 5.1 92 12 [5.5–18] 12.8 8.9
6 258 30 [29–30] 28.7 4.0 80 13 [8–20] 13.2 8.2
9 252 30 [29–30] 28.7 3.5 84 10.5 [4.5–19.5] 12.7 9.4
15 242 30 [29–30] 28.7 3.6 86 12 [5–18] 12.6 8.3
18 234 30 [29–30] 28.9 2.9 82 15 [6–20] 13.6 8.4
21 232 30 [29–30] 28.3 4.7 75 15 [6–19] 13.3 8.3
24 209 30 [29–30] 28.2 5.4 66 10 [7–16] 13.6 12.4
27 172 30 [29–30] 28.6 4.4 52 10.5 [3.5–20] 12.2 10.2
30 106 30 [29–30] 28.0 5.6 18 15 [8–21] 14.9 8.3
33 36 30 [29–30] 28.5 4.3 3 19 [18–21] 19.3 1.5
Year 1 772 30 [29–30] 28.6 4.4 327 12 [5–20] 13.3 10.0
Years 2 and 3 1231 30 [29–30] 28.5 4.4 382 12.5 [6–19] 13.2 9.4
Overall 2003 30 [29–30] 28.5 4.4 709 12 [5–19] 13.3 9.6
Use is shown in a number of pills taken in the preceding 30 days, as reported by the participants of AMPrEP at each quarterly visit. Data are shown separately for those using daily PrEP and those using event-driven PrEP.AMPrEP, Amsterdam PrEP Demonstration Project; IQR, interquartile range; PrEP, preexposure prophylaxis; SD, standard deviation.
aNo data were collected during the consultation after 12 months due to technical problems.
bThe n denotes the number of questionnaires collected at the given time point and regimen. The n for year 1 denotes all questionnaires completed in the first 12 months, whereas for years 2 and 3 denotes all questionnaires completed in the remaining of the study.

Impact on HIV and gonorrhoea

From the transmission model, we calculated that 3740 HIV infections were averted (Fig. 1a; the numbers of new infections are shown in Fig. S1, Supplemental Digital Content, and 1482 QALYs were gained with PrEP over the 10-year period 2018–2027. Gonorrhoea prevalence declined from 0.78% in 2017 to 0.02% in 2027. This resulted in a decline in the number of MSM eligible for PrEP (since a recent gonorrhoea diagnosis is one of the inclusion criteria for PrEP [15]), from 11 435 in 2018 to 5630 in 2027 (Fig. 1b), that is from 5.71% to 2.82% of MSM.

Fig. 1:
The impact of preexposure prophylaxis (PrEP) in a population of 200 000 men who have sex with men (MSM), in 2018–2027.


With the economic model, we calculated the costs of PrEP medication over 2018–2027 at €22 million with daily PrEP and €19 million with a choice of daily and event-driven PrEP. Both programmes were on average cost-effective, when compared to the case without PrEP. Daily PrEP resulted in an average ICER of €217 per QALY gained (Fig. 1c). The programme offering a choice of daily and event-driven PrEP resulted in lower total costs than the total costs without PrEP (Fig. 1d). The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of the PrEP programme being cost-saving (compared to not having a PrEP programme) increased from 42% when offering daily PrEP only to 48% when offering daily and event-driven PrEP.


A programme offering daily PrEP for MSM according to the Dutch PrEP guidelines would be cost-effective. Assuming similar and adequate adherence to both daily and event-driven PrEP implies that a programme offering a choice of daily and event-driven PrEP may have the same health effects as a programme offering only daily PrEP, but the programme offering a choice saves around 14% of the costs of PrEP medication. Providing a choice is thus more likely to be cost-effective and more likely to be cost-saving, compared to a programme offering only daily PrEP. For the Dutch MSM population of 200 000 MSM, we calculated that a programme offering both options resulted in savings of €3 million over 2018–2027 in direct healthcare costs.

Our findings are in agreement with previous modelling work. The benefits of PrEP in reducing HIV incidence among MSM and its cost-effectiveness have been shown in several countries [12,25–32]. Assuming 100% adherence with both daily and event-driven PrEP, Mitchell and colleagues [29] found that event-driven PrEP could substantially reduce programme costs, especially in settings with high drug costs. A cost-effectiveness analysis for MSM in the United Kingdom showed that event-driven PrEP could result in substantial savings [32] and be cost-effective.

Our study is the first modelling study using actual data on the numbers of PrEP pills used by daily PrEP users and by event-driven PrEP users and actual data on the fraction of PrEP users choosing event-driven PrEP (and not daily), in a programme where participants were allowed to change PrEP regime every 3 months. It is also important that we accounted for NG transmission, since that affects the number of MSM being eligible for PrEP. Unfortunately, the duration of AMPrEP was too short to provide statistical evidence for a declining trend in gonorrhoea prevalence and the design of AMPrEP was unsuitable to assess changes in the number of PrEP users.

In this study, we considered a time horizon of 10 years. The benefits of PrEP may not all be realized within 10 years, but this time horizon provides a realistic and relevant evaluation of costs and benefits, since the HIV healthcare sector is drastically changing, due to the development of new antiviral agents, new or expiring patents, circulation of other infections, or changes in sexual behaviour. We assumed the same level of effectivity and adherence for daily and event-driven PrEP, based on evidence from earlier studies [2,3]. There are concerns that nondaily medication may be easier to forget and unexpected (not-planned) sexual contacts may occur. Nevertheless, data from AMPrEP show that precisely the ability to predict or plan sex contacts was one of the main reasons for choosing event-driven PrEP [4]. Also, based on data on CAI events and PrEP medication use as reported daily in the mobile application used by AMPrEP participants, the 3-monthly questionnaires, and the measured intracellular tenofovir levels, we established high levels of adherence among event-driven PrEP users [33]. In addition, HIV incidence was very low among both daily (0.76 infections per 100 person-years, 95% confidence interval [CI] 0.19–3.03) and event-driven (0 infections per 100 person-years, 95% CI 0–3.96) PrEP users in AMPrEP [6], suggesting similar good adherence in both groups.

In conclusion, our study suggests that a nationwide PrEP programme offering MSM a choice of daily and event-driven PrEP is likely to be cost-effective and even cost-saving. Such a programme could result in savings compared to a programme offering daily PrEP only, due to the reduced costs of PrEP medication. In addition, offering a choice could result in more PrEP users, since some individuals may not want or need daily PrEP, and that could lead to a higher level of protection against HIV at the population level [34]. To reduce costs and provide a choice, PrEP programmes should allow the option of daily and event-driven PrEP.


The authors thank the participants of the AMPrEP project and all members of the AMPrEP study group and the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. The authors would like to thank Ardine de Wit for suggestions in setting up the study; Marie-Josee Mangen and Linda Steffers for providing data on costs of HIV testing and HIV care. The authors gratefully acknowledge all participating HIV treatment centres and the data management of Stichting HIV Monitoring for data collection, monitoring, and support.

Funding: This study was funded by a grant from ZonMW (project number 522002003) and Aidsfonds (project number 2014037). The study drug for AMPrEP and an unrestricted research grant were provided by Gilead Sciences (CO-US-276-1712); the funder had no role in study design, data collection, analysis, interpretation, or writing of the report. The H-TEAM initiative is supported by the Aidsfonds Netherlands (2013169), the Stichting Amsterdam Dinner Foundation, Gilead Sciences Europe (PA-HIV-PREP-16–0024), Gilead Sciences (CO-NL-276–4222), Janssen Pharmaceuticals (PHNL/JAN/0714/0005b/1912fde), MAC AIDS Fund, and ViiV Healthcare (3000268822, 3000747780).

Conflicts of interest

There are no conflicts of interest.


1. van Sighem A, Wit F, Boyd A, Smit C, Matser A, Reiss P. Monitoring Report 2019. Human immunodeficiency virus (HIV) infection in the Netherlands. Amsterdam: Stichting HIV Monitoring; 2019. Available at:
2. Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, et al. ANRS IPERGAY Study Group. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015; 373:2237–2246.
3. McCormack S, Dunn D, Desai M, Dolling D, Gafos M, Gilson R, et al. Preexposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016; 387:53–60.
4. Hoornenborg E, Achterbergh RCA, Schim van der Loeff MF, Davidovich U, van der Helm JJ, Hogewoning A, et al. Men who have sex with men more often chose daily than event-driven use of preexposure prophylaxis: baseline analysis of a demonstration study in Amsterdam. J Int AIDS Soc 2018; 21:e25105.
5. Reyniers T, Nostlinger C, Laga M, De Baetseleier I, Crucitti T, Wouters K, et al. Choosing between daily and event-driven preexposure prophylaxis: results of a Belgian PrEP demonstration project. J AIDS 2018; 79:186–194.
6. Hoornenborg E, Coyer L, Achterbergh R, Matser A, Schim van der Loeff M, Boyd A, et al. Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven preexposure prophylaxis in AMPrEP: 2 year results from a demonstration study. Lancet HIV 2019; 6:e447–e455.
7. Vuylsteke B, Reyniers T, De Baetselier I, Nostlinger C, Crucitti T, Buyze J, et al. Daily and event-driven preexposure prophylaxis for men who have sex with men in Belgium: results of a prospective cohort measuring adherence, sexual behavior and STI incidence. J Int AIDS Soc 2019; 22:e25407.
8. World Health Organization. What's the 2+1+1? Event-driven oral preexposure prophylaxis to prevent HIV for men who have sex with men: update to WHO's recommendation on oral PrEP. Geneva: World Health Organization; 2019 (WHO/CDS/HIV/19.8). Available at: [Accessed 1 September 2020]
9. Hoornenborg E, Coyer L, van Laarhoven A, Achterbergh R, de Vries H, Prins M, et al. Change in sexual risk behavior after 6 months of preexposure prophylaxis use: results from the Amsterdam preexposure prophylaxis demonstration project. AIDS 2018; 32:1527–1532.
10. Reitsema M, Heijne J, Visser M, van Sighem A, Schim van der Loeff M, Op de Coul E, et al. Impact of frequent testing on the transmission of HIV and N. gonorrhoeae among men who have sex with men: a mathematical modelling study. Sex Transmit Infect 2020; 96:361–367.
11. Reitsema MT, Steffers L, Visser M, Heijne J, van Hoek AJ, Schim van der Loeff M, et al. Cost-effectiveness of increased HIV testing among men who have sex with men in the Netherlands. AIDS 2019; 33:1807–1817.
12. Reitsema M, van Hoek AJ, Schim van der Loeff M, Hoornenborg E, van Sighem A, Wallinga J, et al. Preexposure prophylaxis for MSM in the Netherlands: impact on HIV and N. gonorrhoeae transmission and cost-effectiveness. AIDS 2020; 34:621–630.
13. Heijman T, Geskus RB, Davidovich U, Coutinho RA, Prins M, Stolte IG. Less decrease in risk behaviour from pre-HIV to post-HIV seroconversion among MSM in the combination antiretroviral therapy era compared with the precombination antiretroviral therapy era. AIDS 2012; 26:489–495.
14. Heymans R, Master A, Bruisten SM, Heijman T, Geskus RB, Speksnijder AG, et al. Distinct Neisseria gonorrhoeae transmission networks among men who have sex with men in Amsterdam, The Netherlands. J Infect Dis 2012; 206:596–605.
15. Dutch Association of HIV-treating physicians. HIV preexposure prophylaxis (PrEP) guideline, The Netherlands. Version 2, April 2019. Available at: [Accessed 1 September 2020]
16. Op de Coul EL, Schreuder I, Conti S, van Sighem A, Xiridou M, van Veen M, et al. Changing patterns of undiagnosed HIV infection in the Netherlands: who benefits most from intensified HIV test and treat policies?. PLoS ONE 2015; 10:e0133232doi: 10.1371/journal.pone.0133232.
17. National Healthcare Institute. Guideline for economic evaluations in healthcare. Available at: [Accessed 1 September 2020]
18. National Healthcare Institute, Cost-effectiveness in practice (in Dutch). 2015. Available at: [Accessed: 20 August 2018]
19. Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, et al. Uptake of preexposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis 2014; 14:820–829.
20. National Institute of Public Health and the Environment. National PrEP pilot for MSM in the Netherlands (in Dutch). Available at: [Accessed 1 September 2020].
21. Fonner VA, Daglish SL, Kennedy CE, Baggaley R, O’reilly KR, Koechlin FM, et al. Effectiveness and safety of oral HIV preexposure prophylaxis for all populations. AIDS 2016; 30:1973–1983.
22. Liegeon G, Antoni G, Pialoux G, Capitant C, Cotte L, Charreau I, et al. Changes in kidney function among men who have sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV preexposure prophylaxis. J Int AIDS Soc 2020; 23:e25420.
23. Aidsfonds. PrEP now available for 50 euro at all pharmacies (in Dutch). 2018. Available at: [Accessed 1 September 2020]
24. Dutch Healthcare Authority (NZa). DBC healthcare products tariff application in Dutch. 2018. Available at: [Accessed 1 September 2020]
25. Juusola JL, Brandeau ML, Owens DK, Bendavid E. The cost-effectiveness of preexposure prophylaxis for HIV prevention in the United States in men who have sex with men. Ann Intern Med 2012; 156:541–550.
26. Schneider K, Gray RT, Wilson DP. A cost-effectiveness analysis of HIV preexposure prophylaxis for men who have sex with men in Australia. Clin Infect Dis 2014; 58:1027–1034.
27. Ouellet E, Durand M, Guertin JR, LeLorier J, Tremblay CL. Cost effectiveness of ‘on demand’ HIV preexposure prophylaxis for noninjection drug-using men who have sex with men in Canada. Can J Infect Dis Med Microbiol 2015; 26:23–29.
28. Drabo EF, Hay JW, Vardavas R, Wagner ZR, Sood N. A cost-effectiveness analysis of preexposure prophylaxis for the prevention of HIV among Los Angeles County men who have sex with men. Clin Infect Dis 2016; 63:1495–1504.
29. Mitchell K, Dimitrov D, Hughes J, Xia F, Donnell D, Amico K, et al. In what circumstances could nondaily preexposure prophylaxis for HIV substantially reduce program costs?. AIDS 2018; 32:809–818.
30. van de Vijver DA, Richter AK, Boucher C, Gunsenheimer-Bartmeyer B, Kollan C, Nichols B, et al. Cost-effectiveness and budget effect of preexposure prophylaxis for HIV-1 prevention in Germany from 2018 to 2058. Euro Surveill 2019; 24:1800398doi: 10.2807/1560-7917.ES.2019.24.7.1800398.
31. Nichols BE, Boucher CA, van der Valk M, Rijnders BJ, van de Vijver DA. Cost-effectiveness analysis of preexposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study. Lancet Infect Dis 2016; 16:1423–1429.
32. Cambiano V, Miners A, Dunn D, McCormack S, Ong K, Gill ON, et al. Cost-effectiveness of preexposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation. Lancet Infect Dis 2018; 18:85–94.
33. Jongen V, Hoornenborg E, van den Elshout M, Boyd A, Zimmermann H, Coyer L, et al. Adherence to event-driven PrEP among men who have sex with men in Amsterdam, the Netherlands: analysis based on online diary data, 3-monthly questionnaires and dried blood spots. J Int AIDS Soc 2021; in press.
34. Liu A, Coleman K, Vittinghoff E, Turner C, Vinson J, Walker N, et al. Assessing the PrEP continuum in the San Fansisco Bay Area: the quickie mobile survey. CROI 2019; abstract number 973. Available at: [Accessed 10 September 2020]

cost-effectiveness; daily preexposure prophylaxis; economic analysis; event-driven preexposure prophylaxis; HIV; men who have sex with men; preexposure prophylaxis; transmission model

Supplemental Digital Content

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