An update on the HIV epidemic in the Netherlands A selection of findings from the SHM Monitoring Report 2018 Peter Reiss 19 November 2018 it’s a pleasure to discuss a selection of findings from this year’s Stichting HIV Monitoring report. Please browse through the report at your leasure for more details.

A special thank you to: SHM Special reports on: Expert clinical and Ard van Sighem Sima Zaheri Ferdinand Wit Mariska Hillebregt Colette Smit Sonia Boender Catriona Ester Daniela Bezemer Special reports on: Amsterdam Cohort Studies Amy Matser Ward van Bilsen Maria Prins Curacao Diederik van de Wetering Gonneke Hermanides Ashley Duits Ard van Sighem Expert clinical and public health advisors Joop Arends Kees Brinkman Suzanne Geerlings Frank Kroon Liesbeth van Leeuwen Jeanine Nellen Kees van Nieuwkoop Eline Op de Coul Jan Prins Clemens Richter Annemarie van Rossum Marc van der Valk Anne Wensing Tom Wolfs

Acknowledgements Amsterdam UMC, AMC site, Amsterdam: M. van der Valk*, S.E. Geerlings, A. Goorhuis, J.W. Hovius, T.W. Kuijpers, B. Lempkes, F.J.B. Nellen, D. Pajkrt, T. van der Poll, J.M. Prins, P. Reiss, H.J. Scherpbier, M. van Vugt, W.J. Wiersinga, F.W.M.N. Wit, M. van Duinen, J. van Eden, A. Hazenberg, A.M.H. van Hes, F.J.J. Pijnappel, S.Y. Smallhout, A.M. Weijsenfeld, S. Jurriaans, N.K.T. Back, H.L. Zaaijer, B. Berkhout, M.T.E. Cornelissen, C.J. Schinkel, K.C. Wolthers. Emma Kinderziekenhuis (Amsterdam UMC, AMC site): D. Pajkrt, H.J. Scherpbier, C. de Boer, A. van der Plas, A.M. Weijsenfeld. Amsterdam UMC, Vumc site, Amsterdam: E.J.G. Peters*, M.A. van Agtmael, M. Bomers, K.C.E. Sigaloff, M. Heitmuller, L.M. Laan, C.W. Ang, R. van Houdt, M. Jonges, A.M. Pettersson, J. van Prehn. Admiraal De Ruyter Ziekenhuis, Goes: M. van den Berge, A. Stegeman, S. Baas, L. Hage de Looff, B. Wintermans, J. Veenemans. Catharina Ziekenhuis, Eindhoven: M.J.H. Pronk*, H.S.M. Ammerlaan, E.S. de Munnik, A.R. Jansz, J. Tjhie, M.C.A. Wegdam, B. Deiman, V. Scharnhorst. DC Klinieken Lairesse - Hiv Focus Centrum: A. van Eeden*, M. van der Valk, W. Brokking, L.J.M. Elsenburg, H. Nobel, M. Damen, I.S. Kwa. ETZ: M.E.E. van Kasteren*, M.A.H. Berrevoets, A.E. Brouwer, R. van Erve, B.A.F.M. de Kruijf-van de Wiel, S.Keelan-Pfaf, B. van de Ven, A.G.M. Buiting, J.L. Murck, D.Versteeg. Erasmus MC, Rotterdam: M.E. van der Ende*, H.I. Bax, E.C.M. van Gorp, J.L. Nouwen, B.J.A. Rijnders, C.A.M. Schurink, A. Verbon, T.E.M.S. de Vries-Sluijs, N.C. de Jong-Peltenburg, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, H.J. van den Berg-Cameron, J. de Groot, C.A.B. Boucher, M.P.G Koopmans, J.J.A van Kampen. Erasmus MC–Sophia, Rotterdam: P.L.A. Fraaij, A.M.C. van Rossum, C.L. Vermont, L.C. van der Knaap, E. Visser. Flevoziekenhuis, Almere: J. Branger*, R.A. Douma, C.J.H.M. Duijf-van de Ven. HagaZiekenhuis, Den Haag: E.F. Schippers*, C. van Nieuwkoop, J.M. van IJperen, J. Geilings, G. van der Hut, N.D. van Burgel. HMC (Haaglanden Medisch Centrum), Den Haag: E.M.S. Leyten*, L.B.S. Gelinck, F. Mollema, S. Davids-Veldhuis, A.Y. van Hartingsveld, G.S. Wildenbeest, E. Heikens. Isala, Zwolle: P.H.P. Groeneveld*, J.W. Bouwhuis, A.J.J. Lammers. S. Kraan, A.G.W. van Hulzen, M.S.M. Kruiper, G.L. van der Bliek, P.C.J. Bor, P. Bloembergen, M.J.H.M. Wolfhagen, G.J.H.M. Ruijs. Leids Universitair Medisch Centrum, Leiden: F.P. Kroon*, M.G.J. de Boer, H. Scheper, H. Jolink, W. Dorama, N. van Holten, E.C.J. Claas, E. Wessels. Maasstad Ziekenhuis, Rotterdam: J.G. den Hollander*, K. Pogany, A. Roukens, M. Kastelijns, J.V. Smit, E. Smit, D. Struik-Kalkman, C. Tearno, T. van Niekerk, O. Pontesilli. Maastricht UMC+, Maastricht: S.H. Lowe*, A.M.L. Oude Lashof, D. Posthouwer, R.P. Ackens, K. Burgers, J. Schippers, B. Weijenberg-Maes, I.H.M. van Loo, T.R.A. Havenith. MC Slotervaart, Amsterdam: J.W. Mulder*, S.M.E. Vrouenraets, F.N. Lauw, M.C. van Broekhuizen, M. Kroeze, D.J. Vlasblom, P.H.M. Smits. MC Zuiderzee, Lelystad: S. Weijer*, R. El Moussaoui, A.S. Bosma. Medisch Centrum Leeuwarden, Leeuwarden: M.G.A.van Vonderen*, L.M. Kampschreur, S. Faber, J Weel. Medisch Spectrum Twente, Enschede: G.J. Kootstra*, C.E. Delsing, M. van der Burg-van de Plas, H. Heins. Noordwest Ziekenhuisgroep, Alkmaar: W. Kortmann*, G. van Twillert*, R. Renckens, D. Ruiter-Pronk, F.A. van Truijen-Oud, J.W.T. Cohen Stuart, M. Hoogewerf, R. Jansen, W. Rozemeijer W. A. van der Reijden, J.C. Sinnige. OLVG, Amsterdam K. Brinkman*, G.E.L. van den Berk, W.L. Blok, P.H.J. Frissen, K.D. Lettinga W.E.M. Schouten, J. Veenstra, C.J. Brouwer, G.F. Geerders, K. Hoeksema, M.J. Kleene, M. Knapen, I.B. van der Meché, E. Mulder-Seeleman, A.J.M. Toonen, S. Wijnands, D. Kwa. Radboudumc, Nijmegen: R. van Crevel*, M. Keuter, H.J.M. ter Hofstede, A.S.M. Dofferhoff, S.S.V. Henriet, K. van Aerde, J. Hoogerwerf, O. Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, R. Strik-Albers, J. Rahamat-Langendoen, F.F. Stelma, D. Burger. Rijnstate, Arnhem: E.H. Gisolf*, R.J. Hassing, M. Claassen, G. ter Beest, P.H.M. van Bentum, N. Langebeek, R. Tiemessen, C.M.A. Swanink. Spaarne Gasthuis, Haarlem: S.F.L. van Lelyveld*, R. Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, N. Bermon, W.A. van der Reijden, R. Jansen, B.L. Herpers, D.Veenendaal. Medisch Centrum Jan van Goyen, Amsterdam: D.W.M. Verhagen, M. van Wijk. Universitair Medisch Centrum Groningen, Groningen: W.F.W. Bierman*, M. Bakker, J. Kleinnijenhuis, E. Kloeze, E.H. Scholvinck, Y. Stienstra, C.L. Vermont, M. Wouthuyzen-Bakker, A. Middel, A. Boonstra, H. de Groot-de Jonge, P.A. van der Meulen, D.A. de Weerd, H.G.M. Niesters, C.C. van Leer-Buter, M. Knoester. Universitair Medisch Centrum Utrecht, Utrecht: A.I.M. Hoepelman*, J.E. Arends, R.E. Barth, A.H.W. Bruns, P.M. Ellerbroek, T. Mudrikova, J.J. Oosterheert, M.J.A. de Regt, E.M. Schadd, M.W.M. Wassenberg, M.A.D. van Zoelen, K. Aarsman, B.M.G. Griffioen-van Santen, I. de Kroon, C.S.A.M. van Rooijen, M. van Berkel, F. Verduyn-Lunel, A.M.J. Wensing. Wilhelmina Kinderziekenhuis, UMC Utrecht, Utrecht: L.J. Bont, S.P.M. Geelen, Y.G.T. Loeffen, T.F.W. Wolfs, N. Nauta. Sint Elisabeth Hospitaal, Willemstad, Curaçao: J.F. Schattenkerk, F. Muskiet, R. Voigt, D. van de Wetering, I. van der Meer. Coordinating centre: P. Reiss, D.O. Bezemer, A.I. van Sighem, C. Smit, F.W.M.N. Wit, S. Zaheri, M. Hillebregt, A. de Jong, T. Woudstra, D. Bergsma, S. Grivell, M. Raethke, R. Meijering, T. Rutkens, L. de Groot, M. van den Akker, Y. Bakker, M. Bezemer, N. Brétin, E. Djoechro, A. el Berkaoui, J. Geerlinks, E. Kruijne, C. Lodewijk, E. Lucas, R. van der Meer, L. Munjishvili, F. Paling, B. Peeck, C. Ree, R. Regtop, Y. Ruijs, L. van de Sande, M. Schoorl, P.Schnörr, E. Tuijn, L. Veenenberg, S. van der Vliet, E.C. de Witte, B. Tuk. 3

Topics Epidemic trends in diagnosis and treatment initiation over time Treatment outcome and the continuum of care Initial treatment regimens Ageing and comorbidity, including hepatitis C co-infection Conclusions It is impossible to comprehensively review all of the findings in this year’s report in detail. What I’ll do is briefly touch on a selection of pertinent issues in relation to the main topics listed here, ending with a couple of conclusions.

Annual number of new HIV diagnoses has continued to decline in 2017, but only gradually Around 750 new diagnoses in 2017 69% in MSM 23% through heterosexual contact 7% through other or unknown mode of acquisition The estimated total number of annual new diagnoses continues to stand around 1000 cases. Compared to our previous report the proportion of new cases involving MSM has now increased from 67 to 71% and the proportion of new cases involving heterosexual transmission has declined from 27 to 23%. The trend from earlier years for new cases to increasingly occur in relatively older individuals continues both among MSM and individuals infected through heterosexual transmission.

Geographical region of origin of those newly diagnosed with HIV MSM Other adult men and women 25% of newly diagnosed persons in 2017 were >50 years old: More often the case for Dutch MSM & other Dutch men and women than for those from other regions of origin than the Netherlands

Where are people being diagnosed? Data from 2015 onwards

At time of diagnosis far too many have likely already been infected much longer In 2017, 45% overall of newly-diagnosed individuals had AIDS and/or CD4 cells <350/mm3 when entering care 63% 52% 37% Late presentation even more common in those over 45 at time of entry into care (2015 or later) % late presenters >45 yrs <25 yrs MSM 50% 23% Other men 71% 48% Women 59% 26%

Early diagnosis needs to be improved Nationwide: slow improvement in MSM, but not in other men or women Of those newly diagnosed in 2017: 26% of MSM & 4% of other men & women had a last negative test < 6 months before diagnosis Repeated HIV testing amongst MSM has also improved the rate at which these men are being diagnosed with recent HIV infection. When defined as known to have had a documented negative test within the last 6 months, 19% of newly diagnosed MSM in 2013 had recent infection. When also taking into account other evidence of recent infection for example the presence of symptoms of primary HIV infection, the proportion of MSM diagnosed with recent infection increases to 31% in 2013. This illustrates the importance for both health care professionals and individuals at risk to be aware of the signs and symptoms of primary HIV infecftion.

Universal rapid start of treatment, regardless of CD4 count, has become the norm Proportion starting cART within 6 months after HIV diagnosis, according to CD4 count at time of diagnosis 2017: 91% with CD4 ≥ 500 cells/mm3 started cART within 6 months of diagnosis (81% in 2015) Looking at the issue of startting treatment in a bit more detail, one can see that with time treatment is generally being initiated at earlier stages of infection, although there clearly remains room for further improvement. A promising trend is that, whereas last year only 29 percent of persons diagnosed with a CD4 count over 500 had begun treatment within the next 6 months, this proportion in 2013 had risen to 41 percent.

In 2017 >85% of people entering care started treatment within 1 month (in 2016: 75%) Time between entry into care and initiation of combination antiretroviral therapy (cART) from 2007-2017. within 21-31 days within 14-20 days within 7-13 days Looking at the issue of startting treatment in a bit more detail, one can see that with time treatment is generally being initiated at earlier stages of infection, although there clearly remains room for further improvement. A promising trend is that, whereas last year only 29 percent of persons diagnosed with a CD4 count over 500 had begun treatment within the next 6 months, this proportion in 2013 had risen to 41 percent. within 1 week same day

Universal rapid treatment initiation fairly uniform across the 26 Netherlands treatment centres Proportion of patients started on cART within 6 months after entering care, by year & treatment centre size Another important comorbiditiy is liver disease related to viral hepatitis co-infection. Concerning hepatitis C, we can see that the uptake of treatment for hepatitis C, including treatment with first generation direct acting antivirals, in the HIV-infected population in care has clearly increased over time. Nonetheless, currently just over 900 patients with HIV in care remain in need of curative treatment for their HCV infection. These findings will be discussed in more detail by Colette Smit, later this morning. > 700 pts < 400 pts 400-700 pts

Heading towards epidemic control Number of newly-acquired HIV infections as estimated using ECDC modelling tool is declining 450 (95% CI 250-550) as is the estimated number of people living with undiagnosed HIV Expanding testing and prevention options, including PrEP, tailored to each community’s needs, will be required to further improve our capacity for early diagnosis and treatment, and really achieve epidemic control 2,300 (95% CI 1900-2700)

Topics Epidemic trends in diagnosis and treatment initiation over time Treatment outcome and the continuum of care Initial treatment regimens Ageing and comorbidity, including hepatitis C co-infection Conclusions It is impossible to comprehensively review all of the findings in this year’s report in detail. What I’ll do is briefly touch on a selection of pertinent issues in relation to the main topics listed here, ending with a couple of conclusions.

Viral suppression rates on cART are high across the 26 Netherlands treatment centres Percentages of treatment-naive patients with a plasma HIV RNA level <400 copies/ml at 6 months (minimum and maximum: 3-9 months) after the start of cART across all HIV treatment centres. Another important comorbiditiy is liver disease related to viral hepatitis co-infection. Concerning hepatitis C, we can see that the uptake of treatment for hepatitis C, including treatment with first generation direct acting antivirals, in the HIV-infected population in care has clearly increased over time. Nonetheless, currently just over 900 patients with HIV in care remain in need of curative treatment for their HCV infection. These findings will be discussed in more detail by Colette Smit, later this morning. > 700 pts < 400 pts 400-700 pts

Increasing proportions of patients on cART are living with higher CD4 counts ≥ 750 cells/mm3 500-749 cells/mm3 Treatment responses remain generally excellent. These figures show the short- and longterm treatment responses in individuals who initiated combination ART without prior treatment experience, whose viral load was measured with an assay with a lower limit of detection of 50 copies or less, and who continue to remain on treatment. As can be seen in the top graph, close to 90% of these patients in recent years manage toachieve viral suppression at one year, and of the ones who continue on treatment, more than 90% sustain suppression out to 13.5 years of follow-up.

Continuum of care: persons diagnosed, linked to care, retained in care, on cART, and suppressed 2,300 undiagnosed (95% CI 1,900-2,700) 90-90-90 by 2020 2015 figures: all: 88-88-93 & 72% MSM: 90-91-94 & 77% 1,300 undiagnosed (95% CI 1,100-1,600) 90-90-90 by 2020

Dissecting the cascade of care further... MSM by region of origin Other men by region of origin Women by region of origin All in care by age

Care continuum in children who acquired HIV during pregnancy & delivery, or later in childhood By age and route of HIV acquisition

Topics Epidemic trends in diagnosis and treatment initiation over time Treatment outcome and the continuum of care Initial treatment regimens Ageing and comorbidity, including hepatitis C co-infection Conclusions It is impossible to comprehensively review all of the findings in this year’s report in detail. What I’ll do is briefly touch on a selection of pertinent issues in relation to the main topics listed here, ending with a couple of conclusions.

First-line cART regimens 2013-2017 Treatment responses remain generally excellent. These figures show the short- and longterm treatment responses in individuals who initiated combination ART without prior treatment experience, whose viral load was measured with an assay with a lower limit of detection of 50 copies or less, and who continue to remain on treatment. As can be seen in the top graph, close to 90% of these patients in recent years manage toachieve viral suppression at one year, and of the ones who continue on treatment, more than 90% sustain suppression out to 13.5 years of follow-up.

Shifts in first-line cART regimens 2013-2017 2014 ABC/3TC/DTG TDF/FTC/EVGc 2015 2016 2017 Treatment responses remain generally excellent. These figures show the short- and longterm treatment responses in individuals who initiated combination ART without prior treatment experience, whose viral load was measured with an assay with a lower limit of detection of 50 copies or less, and who continue to remain on treatment. As can be seen in the top graph, close to 90% of these patients in recent years manage toachieve viral suppression at one year, and of the ones who continue on treatment, more than 90% sustain suppression out to 13.5 years of follow-up. TAF/FTC/DTG TDF/FTC/DTG TAF/FTC/EVGc

Durability of first-line regimens has improved Kaplan-Meier estimate of time on initial regimen by calendar year period of initiation (log-rank test p<0.001). 2011-2017 Legend: cART=combination antiretroviral therapy.

Reasons for discontinuing first-line regimen in the first 12 months (2013-2017) Simplification/ new drugs available Toxicity Still on initial regimen Virologic failure

Topics Epidemic trends in diagnosis and treatment initiation over time Treatment outcome and the continuum of care Initial treatment regimens Ageing and comorbidity, including hepatitis C co-infection Conclusions It is impossible to comprehensively review all of the findings in this year’s report in detail. What I’ll do is briefly touch on a selection of pertinent issues in relation to the main topics listed here, ending with a couple of conclusions.

Increasing age of people in care Median age of people in care = 50 years In 2017: 50+ years:48% 60+ years:18% The population of patients with HIV in care fortunately has aged a bit further. Currently 39 percent of patients is older than 50, 13 percent is already older than 60. As a result of aging we see an increase in the incidence of aging-related comorbidities.

Comorbidity and multimorbidity increasingly prevalent with rise in age Adult population in care in 2017. The numbers on top of each bar represent the number of individuals contributing data to that age category .

Reflected in deaths increasingly being caused by such co-morbidities Absolute numbers of deaths by cause and calendar period since the introduction of cART in 1996 Numbers on top of each bar represent the number of individuals that were at risk during that calendar period

Treatment for HCV co-infection over time Treatment for HCV co-infection over time Rapid uptake of (new) DAA combination regimens SVR12 rate 97% in 790 patients who completed treatment with one of the novel DAA regimens & sufficient follow-up post-treatment sofosbuvir+ledipasvir sofosbuvir+daclatasvir Another important comorbiditiy is liver disease related to viral hepatitis co-infection. Concerning hepatitis C, we can see that the uptake of treatment for hepatitis C, including treatment with first generation direct acting antivirals, in the HIV-infected population in care has clearly increased over time. Nonetheless, currently just over 900 patients with HIV in care remain in need of curative treatment for their HCV infection. These findings will be discussed in more detail by Colette Smit, later this morning.

Incidence of primary HCV declining in MSM? Reinfection remains a significant concern

Conclusions Epidemic trends, diagnosis and treatment, the continuum of care, and ART We see a continued, but still only gradual, decline in the annual number of newly diagnosed individuals Late presentation generally still remains far too common Improvements in early diagnosis are possible, as suggested by the data from Amsterdam in MSM More testing and prevention options, including PrEP, tailored to each community’s needs, will be needed to achieve more rapid epidemic control The continuum of care is generally looking good, but gaps need to be minded! Immediate treatment after diagnosis, regardless of CD4 count, seems to have been universally adopted Initial ART has shifted further towards integrase inhibitor-based regimens, resulting in rapid viral suppression in the majority of patients In summary…….

Conclusions Ageing, comorbidities, and HCV co-infection More than half of patients over 60 have 1 or 2, and almost 10 percent 3 or more comorbidities, which increasingly affects clinical management and health outcomes Unrestricted access to DAAs against HCV has resulted in continued rapid treatment uptake, high rates of cure, and fewer people remaining in need of effective HCV treatment As a result HCV incidence may be starting to decline, but elimination of HCV infection from the population with HIV in the Netherlands is likely to require additional measures, including optimized screening, prevention and risk counselling Read slide….

For further information Please visit our website (www.hiv-monitoring.nl) and read or download the new digital HIV Monitoring Report. Online PDF, with appendix figures and tables included All figures available separately as powerpoint file at www.hiv-monitoring.nl Summary and Recommendations on website & in print Read slide….