HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study

Colette Smit,E Wttewaal,E Tuijn,W Kortmann,B Peeck,M Groters,E Heikens,B Berkhout,K.C.E Sigaloff,J.L Murck,D Ruiter-Pronk,C.M.A Swanink,K.J Lelivelt,A.J.M Toonen,M Bezemer,H Blaauw,N Bassant,S Wijnands,P Schnörr,J Veenstra,M De Haan,L Scheiberlich,G Ter Beest,M Vriesde,J Van Eden,L Van De Sande,F Verduyn-Lunel,M.C.A Wegdam,S Zaheri,A.I Van Sighem,S Davids-Veldhuis,N Bermon,D.N.J Van Den Bersselaar,G.S Wildenbeest,J De Groot,M Van Den Berge,T Van Der Poll,S.F.L Van Lelyveld,H.J.M Ter Hofstede,J.E.A Van Beek,J Geilings,E.C Witte,C.J.H.M Duijf-Van De Ven,N Brétin,C.J Brouwer,K Aarsman,M Albers,A Hazenberg,R Renckens,F.P Kroon,F.F Stelma,B.M.G Griffioen-Van Santen,P.H.M Van Bentum,Maria Prins,B Lempkes,R Regtop,M.J Kleene,E Mulder-Seeleman,Marc Van Der Valk,A De Jong,I.B Van Der Meché,S.Y Smalhout,A Al Moujahid,G.H.J Wagenvoort,F.A Van Truijen-Oud,N.D Van Burgel,G.F Geerders,R Strik-Albers,C Lodewijk,B Van De Ven,A El Berkaoui,S Keelan-Phaf,J Van Der Swaluw,R Tiemessen,H Nobel,A.M Weijsenfeld,O Pontesilli,Y Ruijs,B Weijenberg-Maes,M.E.E Van Kasteren,D.A De Weerd,H Jolink,W Dorama,Anne Boerekamps,R Van Erve,D Struik-Kalkman,M.S.M Kruiper,A Scheigrond,M Marneef,Kees Brinkman,E Kruijne,T Rutkens,E.M Schadd,J.M Van Ijperen,D Posthouwer,L Hage De Looff,S Kraan,J.W Bouwhuis,E Kloeze,L Veenenberg,L.M.M Van Der Prijt,F.J.J Pijnappel,I De Kroon,M.G.J De Boer,M Van Berkel,C.S.A.M Van Rooijen,Janke Schinkel,R El Moussaoui,L Munjishvili,Y Bakker,G Van Der Hut,M Heitmuller,Peter Reiss,N Van Holten,F.J.B Nellen,S Baas,B.A.F.M De Kruijf-Van De Wiel,A.J.J Lammers,W.A Van Der Reijden,R Steeman-Bouma,C Tearno,Anders Boyd,G.L Van Der Bliek,E Djoechro,A.S Cents-Bosma,N.C De Jong-Peltenburg,A.M.H Van Hes,Martim Melo ,Marc R Kok ,Reinout Van Crevel ,A G M Buiting ,Reshma Autar ,Ymkje Stienstra ,Mariska Hillebregt ,Merel M C Lambregts ,Marjolein Knoester ,André Boonstra ,Anna H E Roukens ,Marvin A.h Berrevoets ,H G M Niesters ,Michiel A Van Agtmael ,Marlies E Van Wolfswinkel ,Lcpgm De Groot ,Bas Wintermans ,Annelies Verbon ,Marjo H J Knapen ,Marieke Hoogewerf ,Marjan Wouthuyzen‐Bakker ,Wouter Rozemeijer ,Margreet Bakker ,J W T Cohen Stuart ,Thomas Havenith ,Inge H M Van Loo ,Femke Mollema ,Arne Van Eeden ,W Blok ,K Pogány ,Els Wessels ,Jan Jelrik Oosterheert ,Katja C Wolthers ,Andrew L Adams ,Eric C M Van Gorp ,Roos E Barth ,Ferdinand W Wit ,Nienke Langebeek ,Judith Branger ,Douwe F Postma ,S M Faber ,Lennert Slobbe ,Suzanne E Geerlings ,Karin J T Grintjes-Huisman ,Cees Van Nieuwkoop ,Kamilla D Lettinga ,Marije K Bomers ,Jan L Nouwen ,Derek Bergsma ,Eline Op De Coul ,Monique Keuter ,C Wim Ang ,Stefan Van Der Vliet ,M J H Pronk ,Tania Mudrikova ,Janneke E Stalenhoef ,Gitte Van Twillert ,Hans L Zaaijer ,Astrid G W Van Hulzen ,Robert Soetekouw ,Dominique W M Verhagen ,J A Schippers ,Charles A Boucher ,Els Van Nood ,Marlies Van Duinen ,Petra Bor ,Marcel Jonges ,Jeroen J.a Van Kampen ,Coretta Van Leer-Buter ,Kirsten Visser ,L Elsenburg ,Anton S M Dofferhoff ,David M Burger ,Janette Rahamat‐Langendoen ,Volkher Scharnhorst ,Sylvia B Debast ,Casper Rokx ,Liedewij Laan ,Michelle Broekhuizen ,Annemarie E Brouwer ,Arjan Stegeman ,L M Van Zonneveld ,Wilma Brokking ,Jacobien Veenemans ,Guido E.l Van Den Berk ,Arjen R Jansz ,Joppe W Hovius ,Birgit Deiman ,Johanneke Kleinnijenhuis ,T.j Woudstra ,Fanny N Lauw ,Jan C Sinnige ,T.g.c.m Van Niekerk ,Robin Van Houdt ,Marion Cornelissen ,Evertjan Jansen ,Eric Lucas ,Emile F Schippers ,Daniela Bezemer ,Michiel P Van Wijk ,P H P Groeneveld ,Elisabeth H Gisolf ,Ananja Middel ,Bart Rijnders ,A I M Hoepelman ,S M E Vrouenraets ,Kristina Burgers ,Suzanne Jurriaans ,Heidi S M Ammerlaan ,Eliane M S Leyten ,Ronald Jansen ,Annemarie M J Wensing ,Marion Koopmans ,Reuben Douma ,Jan G Den Hollander ,Corine E Delsing ,Theodora E M S De Vries-Sluijs ,Abraham Goorhuis ,Jesper Smit ,Jeroen H T Tjhie ,Selwyn H Lowe ,Matthijs Plas ,Robin Ackens ,Christian Schinkel ,Robert Jan Hassing ,G J Kootstra ,Olivier Richel ,David Kwa ,Bjorn L Herpers ,P A Van Der Meulen ,Mark A A Claassen ,W E M Schouten ,Nicole K T Back ,E S De Munnik ,Jacobien J Hoogerwerf ,Jan Den Hollander ,Jan M Prins ,Maartje Schoorl ,Eric C J Claas ,Jeannine Nellen ,Astrid M L Oude Lashof ,Wouter F W Bierman ,Erica J Peters ,Carolina A M Schurink ,L B S Gelinck ,Michèle Van Vugt ,Linda M Kampschreur ,W Joost Wiersinga ,Marit G A Van Vonderen ,Astrid M Newsum ,Pauline M Ellerbroek ,Rob Schuurman ,Cornelis L P Van De Ree ,Roelien A M Meijering ,Marjan Van Den Akker ,Dick Veenendaal ,Hannelore I Bax ,Joop E Arends ,Anke H W Bruns ,T.j.w Van De Laar ,Marina De Regt ,Henk Scheper ,Anne Q Reuwer ,Berend J Van Welzen ,H De Jonge ,Fleur P Paling

doi:10.1016/s2352-3018(20)30301-5

Colette Smit, E Wttewaal + Show 291 more

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https://doi.org/10.1016/s2352-3018(20)30301-5

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Abstract

In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015. In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years. Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5·2 per 1000 person-years [95% CI 5·0-5·5]). The highest incidence was observed in men who have sex with men (MSM; 7·7 per 1000 person-years [7·3-8·2]) and was lower in people who inject drugs (PWID; 1·7 per 1000 person-years [0·7-4·1]) and other key populations (1·0 per 1000 person-years [0·8-1·2]). In MSM, incidence increased in 2007 to 14·3 per 1000 person-years and fluctuated between 8·7 and 13·0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6·1 cases per 1000 person-years and remained steady between 4·1 and 4·9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26·9 per 1000 person-years [95% CI 23·9-30·3]). The highest incidence rate was observed in MSM (38·5 per 1000 person-years [33·9-43·7]) and was lower in PWID (10·9 per 1000 person-years [3·5-33·8]) and other key populations (8·9 per 1000 person-years [6·3-12·5]). In MSM, reinfection incidence fluctuated between 38·0 and 88·9 per 1000 person-years from 2006 to 2015, reaching 55·6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41·4 per 1000 person-years, followed by further decreases to 24·4 per 1000 person-years in 2017 and 11·4 per 1000 person-years in 2019. The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. Dutch Ministry of Health, Welfare, and Sport.

Highlights

During the 2000s, the incidence rate of hepatitis C virus (HCV) infections rapidly increased in individuals with HIV across most of Europe.[1]
Added value of this study In the Netherlands, we report that the incidence of both primary infection and reinfection with HCV has substantially decreased in men who have sex with men (MSM) with HIV within the first year after unrestricted access to direct-acting antivirals (DAAs) treatment, it remained steady for the following 4 years
We described the numbers of primary HCV infections and HCV reinfection and the proportion of the total infections according to key population group

Summary

Introduction

During the 2000s, the incidence rate of hepatitis C virus (HCV) infections rapidly increased in individuals with HIV across most of Europe.[1] Treatment at the time was confined to interferon-based regimens with sub optimal sustained virological response rates.[2] Coupled with the low rates of spontaneous clearance after infection[3] and a prolonged, clinically asymptomatic disease course, a substantial proportion of individuals co-infected with HIV and HCV had active HCV replication and were thereby causing onward transmission of HCV.[4]. Modelling studies specific to PWID and MSM with HIV have shown that reductions in the incidence and prevalence of HCV could be obtained for most settings when treatment coverage substantially increases.[7,8] data from observational studies confirming these reports are few in number and most have short follow-up

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