In this project, we assess the impact of immediate initiation of combination antiretroviral therapy (cART), frequent testing, partner notification, and pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in the Netherlands. We examine their impact on the transmission of HIV and the transmission of other sexually transmitted infections (STI), with N. gonorrhoea (NG) as example. Furthermore, we investigate the cost-effectiveness of these strategies. 

Project summary

Background

MSM account for the majority of new HIV diagnoses in the Netherlands, with approximately 65% of 850 new HIV diagnoses in 2015 being MSM. Over the years, attention has focused on numerous preventive measures or strategies. In this project, we examine the individual and combined impact of four measures: immediate initiation of cART, frequent testing, partner notification, and PrEP. We examine their impact on the transmission of HIV and N. gonorrhoea (NG), as well as their cost-effectiveness.

Methods

We developed an agent-based transmission model that simulated the sexual life of each individual. Men in the model form steady and casual partnerships with other MSM and can acquire HIV or NG via condomless anal intercourse with their partners. Parameters relating to sexual behaviour were estimated using data from the Amsterdam Cohort Study and the Network Study among MSM in Amsterdam. The progression of HIV infection was modelled using data from Stichting HIV Monitoring. Frequency of HIV/STI testing was estimated based on data from the national database of STI clinics in the Netherlands. The model was fitted to data on HIV diagnoses and data on gonorrhoea positivity rate. Subsequently, we developed a stochastic economic model that used data from the transmission model as input. Direct healthcare costs were calculated using an activity-based costing approach, identifying all individual activities and costed the time, tests, and medication used. We included costs of medical consultations (at STI clinics, general practitioners, hospitals, or HIV treatment centres), laboratory tests, cART medication, treatment of HIV/AIDS patients with opportunistic infections, and treatment of NG infections. For each intervention, costs relating only to the specific intervention were also included. Health effects were expressed in quality-adjusted life-years (QALY). The incremental cost-effectiveness ratio (ICER) was calculated, showing the additional costs per QALY gained with the intervention, compared to the current situation. According to Dutch guidelines, the threshold of €20,000 per QALY gained was used for the cost-effectiveness of an intervention. 

Results

Our analyses show that immediate cART initiation can lead to a reduction of 25% in the number of new HIV infections over the first ten years of its implementation. Immediate cART initiation can be cost-effective over the first ten years, compared to deferred cART initiation according to the old treatment guidelines. Frequent HIV/STI testing, in combination with immediate cART initiation, can result in even higher reductions in HIV incidence and NG prevalence and be cost-effective. Regular HIV/STI testing every six months among MSM with more than ten partners in the previous 6 months or MSM with a recent gonorrhoea diagnosis can result in major numbers of HIV and NG infections being prevented with relatively low numbers of HIV/STI tests. Expanding biannual testing to all MSM will result in greater numbers of prevented infections, but more tests are needed to prevent one infection. Biannual testing among all MSM may not be cost-effective. On the other hand, biannual testing among high-risk MSM can be cost-effective, but it will not be sufficient to bring the number of new HIV infections to zero. Further, we investigated the effects of a nationwide PrEP programme for MSM at high risk to acquire HIV, according to the Dutch guidelines on PrEP use. After ten years, the programme with daily PrEP can result in a 61% reduction in HIV incidence and 72% reduction in gonorrhoea prevalence. Daily PrEP was cost-effective in 91% of our simulations without changes in condom use and in 73% of the simulations with reduced condom use. A PrEP programme offering a choice between daily and event-driven PrEP was cost-effective in 94% of the simulations and resulted in €3 million savings in healthcare costs. 

Conclusions

Our findings indicate that increased HIV/STI testing and PrEP among MSM at high risk to acquire HIV can result in considerable reductions in HIV/STI transmission and be cost-effective. However, targeting only MSM at high risk may not be sufficient to bring the number of new HIV infections to zero; targeting larger subgroups of MSM or combinations of measures will be needed. 

Funding

This work was supported by Aidsfonds (project number 2014037). The study on the cost-effectiveness of event-driven PrEP was partially supported by ZonMw (project number 522002003).

Software and data

Code and data are available from the authors upon request. 

Contributors

  • Maarten Reitsema RIVM
  • Maria Xiridou RIVM
  • Albert Jan van Hoek RIVM
  • Marie-Josee Mangen RIVM
  • Jacco Wallinga RIVM
  • Birgit van Benthem RIVM
  • Janneke Heijne RIVM
  • Maartje Visser RIVM
  • Eline Op de Coul RIVM
  • Ard van Sighem Stichting HIV Monitoring, Amsterdam, The Netherlands
  • Daniela Bezemer Stichting HIV Monitoring, Amsterdam, The Netherlands
  • Maarten Schim van der Loeff Public Health Service Amsterdam & Amsterdam University Medical Centres, Amsterdam, The Netherlands
  • Elske Hoornenborg Public Health Service Amsterdam, Amsterdam, The Netherlands 
  • Maria Prins Public Health Service Amsterdam & Amsterdam University Medical Centres, Amsterdam, The Netherlands. 

Participating organizations 

Publications

Articles in preparation

  • Mangen MJ, Reitsema M, van Hoek AJ, Schim van der Loeff M, van Sighem A, van Benthem B, Wallinga J, Xiridou M. Cost-effectiveness of early initiation of antiretroviral treatment for HIV infection among men who have sex with men. Under review. 
  • Van Hoek AJ, Reitsema M, Xiridou M, van Sighem A, van Benthem B, Wallinga J, Schim van der Loeff M, Prins M, Hoornenborg E, on behalf of the Amsterdam PrEP Project Team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. Offering a choice of daily and event-driven pre-exposure prophylaxis for MSM: a cost-effectiveness analysis. In preparation.

Presentations at conferences

  •  Van Hoek AJ, Reitsema M, Xiridou M, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Prins M, Hoornenborg E. Offering a choice of daily and event-driven PrEP for MSM: a cost-effectiveness analysis. Oral presentation at NCHIV 2019, Amsterdam, 13 November 2019.
  • Reitsema M, van Hoek AJ, Xiridou M, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Prins M, Hoornenborg E, on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. Cost-effectiveness of pre-exposure prophylaxis in MSM with event-driven and daily regimens. Poster presentation P543 at the Joint Meeting of the 23rd ISSTDR and 20th IUSTI, 14-17 July 2019, Vancouver, Canada. 
  • Reitsema M, Visser M, van Benthem B, Wallinga J, van Sighem A, Schim van der Loeff M, Heijne J, Xiridou M. The impact of frequent HIV testing on HIV transmission among MSM. Poster presentation (Number TUPEC294) at International AIDS Conference, Amsterdam, 23-27 July 2018. 
  • Reitsema M, van Hoek AJ, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Xiridou M. PrEP for MSM can result in reductions in HIV infections and can be cost-effective, even with a small decrease in condom use. Poster presentation (Number TUPEC302) at International AIDS Conference, Amsterdam, 23-27 July 2018. 
  • Reitsema M, Steffers L, Wallinga J, van Benthem B, Heijne J, de Munnik S, van Sighem A, Schim van der Loeff M, Xiridou M, Mangen MJ. Cost-effectiveness of increased HIV testing among Dutch MSM. Oral presentation at European Conference on Health Economics (EuHEA), Maastricht, 11-14 July 2018.
  • Reitsema M, Visser M, van Benthem B, Heijne J, Xiridou M. HIV testing among men who have sex with men: how effective can frequent testing be? Poster presentation at International Union against Sexually Transmitted Infection (IUSTI) Congress, Dublin, 27-30 June 2018. 
  • Reitsema M, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Visser M, Xiridou M. The impact of increased HIV/STI testing on the spread of HIV and gonorrhoea among men who have sex with men. Poster presentation at EPIDEMICS, Sitges, 29 November – 1 December 2017. 
  • Reitsema M, Steffers L, Wallinga J, van Benthem B, Visser M, de Munnik S, van Sighem A, Schim van der Loeff M, Xiridou M, Mangen MJ. Cost-effectiveness of increased HIV testing among MSM in the Netherlands. Oral presentation at NCHIV 2017, Amsterdam, 21 November 2017. 
  • Reitsema M, Wallinga J, van Benthem B, Visser M, de Munnik S, van Sighem A, Schim van der Loeff M, Xiridou M, Mangen MJ. The impact of immediate initiation of combination antiretroviral therapy on the HIV epidemic among MSM. Poster presentation at NCHIV 2017, Amsterdam, 21 November 2017. 
  • Reitsema M, Visser M, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Xiridou M. Differences in sexual risk behavior and frequency of STI testing according to HIV serostatus among MSM in the Netherlands. Poster presentation at NCHIV 2016, Amsterdam, 22 November 2016. 
  • Xiridou M, van den Bosch A, van Benthem B, Stolte I, van Sighem A, Wallinga J. The sexual network of men who have sex with men in the Netherlands: who has a relationship with whom? Poster presentation at NCHIV 2015, Amsterdam, 18 November 2015. 

Awards

  • Poster award for: Reitsema M, van Hoek AJ, Xiridou M, Wallinga J, van Benthem B, van Sighem A, Schim van der Loeff M, Prins M, Hoornenborg E, on behalf of the Amsterdam PrEP Project team in the HIV Transmission Elimination Amsterdam (H-TEAM) Initiative. Cost-effectiveness of pre-exposure prophylaxis in MSM with event-driven and daily regimens. Poster presentation P543 at the Joint Meeting of the 23rd ISSTDR and 20th IUSTI, 14-17 July 2019, Vancouver, Canada.