Round Table 1: Epidemiology: the new naive, new epidemiological trends
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1 Moderator: G. Ippolito Facilitator: E. Girardi Round Table 1: Epidemiology: the new naive, new epidemiological trends Panel Discussant: H. Furrer (Swiss Cohort), E. Girardi (ICONA), O. Kirk (EuroSIDA), S. Lo Caputo (ICONA), S. Moreno (CoRIS Cohort), C. Sabin (UK Collaborative HIV Cohort), A. van Sighem (Athena Cohort)
2 Who are new naives in Europe?
3 First Round Table: Epidemiology: the new naïve, new epidemiological trends
4 Q1: who are new naives in Europe? Late presenters EuroSIDA Late diagnosis (role of testing - indicator diseases) Late presentation for care in HIV clinic (delayed entry into care) Patients followed in HIV-clinics but not willing to start cart (i.e. psychiatric comorbidity) Patients followed in ressource-limited settings (Eastern Europe) Illegal immigrants and others with limited access to health care
5 Naïve patients - regional differences SE (n=1059) WCE (n=1290) NE (n=923) ECE (n=1366) EE (n=1964) AR (n=495) Male Transmission MSM Transmission IDU cart HCVAb Age 39 (33-46) CD4 count 434 ( ) 42 (36-49) 447 ( ) 42 (36-50) 432 ( ) 35 (29-42) 369 ( ) 30 (26-36) 415 ( ) SE: South Europe, WCE: West Central Europe, North Europe, ECE: East Central Europe; EE: East Europe & AR: Argentina 36 (31-43) 346 ( ) EuroSIDA Podlekareva, BMC Inf Dis 2012
6 Who are new naïves in Europe Data from ICONA cohort Sergio Lo Caputo for the Icona Foundation Study Group
7 Proportion of patients in follow-up according to gender % 10,442 patients enrolled in ICONA cohort 3457 were enrolled in
8 Characteristics of 3457 patients according to gender ( ) n. (%) female male Total Gender 679 (19,6) 2778 (80,4) 3457 Age Mean age 38 38,7 38,3 Age 40 or less 61,2 % 60,3% 2085 (60,8) Mode of HIV transmission Heterosex 554 (81,6) 813 (29,3) 1367 (39,5) IVDU 55 (8,1) 185 (6,7) 240 (6,9) Homosex (56,1) 1560 (45,1) Other/unk 70 (10,3) 220 (7,9) 290 (8,3) Non Italians 307 (45,4) 430 (15,5) 737 (21,4) HCV Ab 60 (11,7) 257 (12,4) 317 (12,2)
9 Non Italian patients: gender and age differences % of non Italians according to gender Non Italian patients
10 Mode of HIV transmission 40% 35% 30% 25% 20% 15% 10% 5% 0% 37,8 30,7 23,9 7,7 Heterosexual contacts Homo/Bisexual contacts IDU Other/Unknown n=4154 n=3371 n=2621 n=841 60% 50% 40% 30% 20% 10% 0% 46,8% 46,3% 48,2% 44,2% 41,9% 43,1% 32,1% 40,9% 38,4% 39,2% 24,3% 29,7% 23,9% 16,6% 17,1% 9,6% 8,2% 12,7% 5,0% 4,1% 7,7% 7,4% 7,6% 5,2% n=4017 n=1438 n=650 n=890 n=1293 n=2698 Heterosexual contacts Homo/Bisexual contacts IDU Other/Unknown for 2013, 6 months
11 ICONA Study Group BOARD OF DIRECTORS M. Moroni (Chair), G. Angarano, A. Antinori,, O. Armignacco, A. d Arminio Monforte, F. Castelli, R. Cauda,, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C.F. Perno, F. von Schloesser, P. Viale SCIENTIFIC SECRETARY A.d Arminio Monforte, A. Antinori, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti STEERING COMMITTEE Massimo Andreoni, Adriana Ammassari, Andrea Antinori, Antonella d Arminio Monforte, Claudia Balotta, Paolo Bonfanti, Stefano Bonora, Marco Borderi, MRosaria Capobianchi, Antonella Castagna, Francesca Ceccherini-Silberstein, Antonella Cingolani, Paola Cinque, Alessandro Cozzi-Lepri, Antonella d Arminio Monforte, Andrea De Luca, Antonio Di Biagio, Enrico Girardi, Nicola Gianotti, Andrea Gori, Giovanni Guaraldi, Giuseppe Lapadula, Miriam Lichtner, Sergio Lo Caputo, Giordano Madeddu, Franco Maggiolo, Giulia Marchetti, Simone Marcotullio, Laura Monno, Cristina Mussini, Massimo Puoti, Eugenia Quiros Roldan, Stefano Rusconi STATISTICAL AND MONITORING TEAM A.Cozzi-Lepri, P. Cicconi, I. Fanti, T. Formenti, L. Galli, P. Lorenzini PARTICIPATING PHYSICIANS AND CENTERS Italy A. Giacometti, A. Costantini, O. Cirioni (Ancona); G. Angarano, L. Monno, C. Carrisa (Bari); F. Maggiolo, C. Suardi (Bergamo); P. Viale, E. Vanino, G. Verucchi (Bologna); F. Castelli, E. Quiros Roldan, C. Minardi (Brescia); T. Quirino, C. Abeli (Busto Arsizio); P.E. Manconi, P. Piano (Cagliari); J. Vecchiet, K. Falasca (Chieti); L. Sighinolfi, D. Segala (Ferrara); F. Mazzotta, S. Lo Caputo (Firenze); G. Cassola, G. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello (Genova); C. Mastroianni, V. Belvisi (Latina); P. Bonfanti, I. Caramma (Lecco); A. P. Castelli (Macerata); M. Galli, A. Lazzarin, G. Rizzardini, M. Puoti, A. d Arminio Monforte, A.L. Ridolfo, R. Piolini, A. Castagna, S. Salpietro, L. Carenzi, M.C. Moioli, P. Cicconi, G. Marchetti (Milano); C. Mussini, C. Puzzolante (Modena); A. Gori, G. Lapadula (Monza); N. Abrescia, A. Chirianni, M.G. Guida, M. Gargiulo (Napoli); F. Baldelli, D. Francisci (Perugia); G. Parruti, T. Ursini (Pescara); G. Magnani, M.A. Ursitti (Reggio Emilia); R. Cauda, M. Andreoni, A. Antinori, V. Vullo, A. Cingolani, A. d Avino, A. Ammassari, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano (Roma); A. Cattelan (Rovigo); M.S. Mura, G. Madeddu (Sassari); P. Caramello, G. Di Perri, G.C. Orofino, S. Bonora, M. Sciandra (Torino); G. Pellizzer, V. Manfrin (Vicenza).
12 Face-to-face Intercohorts meeting Rome Ard van Sighem Rome, 22 November 2013
13 Acknowledgments Information from Monitoring Report 2013 (hiv-monitoring.nl) Authors Luuk Gras Anouk Kesselring Colette Smit Esther Engelhard Ineke Stolte Peter Reiss Other Daniela Bezemer Louise Dolfing Michael van der Linde Co-authors Eline Op de Coul Jan Prins Kees Brinkman Anne Wensing Ferdinand Wit Joop Arends Clemens Richter Annemarie van Rossum Liesbeth van Leeuwen Maria Prins Gonneke Hermanides Ashley Duits 13
14 Acknowledgments The ATHENA observational cohort has been made possible through the collaborative efforts of the following physicians (*site coordinating physicians) working at Netherlands HIV Treatment Centres: Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam: Prof. dr. J.M. Prins*, Prof. dr. T.W. Kuijpers, Dr. H.J. Scherpbier, Dr. J.T.M. van der Meer, Dr. F.W.M.N. Wit, Dr. M.H. Godfried, Prof. dr. P. Reiss, Prof. dr. T. van der Poll, Dr. F.J.B. Nellen, Prof. dr. J.M.A. Lange, Dr. S.E. Geerlings, Dr. M. van Vugt, Dr. D. Pajkrt, Drs. J.C. Bos, Drs. M. van der Valk, Drs. M.L. Grijsen, Dr. W.J. Wiersinga, Dr. A. Goorhuis, Dr. J.W.R. Hovius. Academisch Ziekenhuis Maastricht, Maastricht: Dr. S. Lowe*, Dr. A. Oude Lashof, Dr. D. Posthouwer. Catharina-ziekenhuis, Eindhoven: Drs. M.J.H. Pronk*, Dr. H.S.M. Ammerlaan. Erasmus Medisch Centrum, Rotterdam: Dr. M.E. van der Ende*, Dr. T.E.M.S. de Vries-Sluijs, Dr. C.A.M. Schurink, Dr. J.L. Nouwen, Dr. A. Verbon, Drs. B.J.A. Rijnders, Dr. E.C.M. van Gorp, Drs. M. van der Feltz. Erasmus Medisch Centrum Sophia, Rotterdam: Dr. G.J.A. Driessen, Dr. A.M.C. van Rossum. Flevoziekenhuis. Almere: Dr. J. Branger*. HagaZiekenhuis, Den Haag: Dr. E.F. Schippers*, Dr. C. van Nieuwkoop, Drs. E.P. van Elzakker. Isala Klinieken, Zwolle: Dr. P.H.P. Groeneveld*, Drs. J.W. Bouwhuis. Kennemer Gasthuis: Drs. R. Soetekouw*, Prof. dr. R.W. ten Kate. Leids Universitair Medisch Centrum, Leiden: Dr. F.P. Kroon*, Prof. dr. J.T. van Dissel, Dr. S.M. Arend, Dr. M.G.J. de Boer, Drs. H. Jolink, Dr. H.J.M. ter Vollaard, Drs. M.P. Bauer. Maasstadziekenhuis, Rotterdam: Dr. J.G. den Hollander*, Dr. K. Pogany. Medisch Centrum Alkmaar, Alkmaar: Drs. G. van Twillert*, Drs. W. Kortmann*, Dr. J.W.T. Cohen Stuart, Dr. B.M.W. Diederen. Medisch Centrum Haaglanden, Den Haag: Dr. E.M.S. Leyten*, Dr. L.B.S. Gelinck. Medisch Spectrum Twente, Enschede: Drs. G.J. Kootstra*, Drs. C.E. Delsing. Onze Lieve Vrouwe Gasthuis, Amsterdam: Prof. dr. K. Brinkman*, Dr. W.L. Blok, Dr. P.H.J. Frissen, Drs. W.E.M. Schouten, Drs. G.E.L. van den Berk. Sint Elisabeth Ziekenhuis, Tilburg: Dr. M.E.E. van Kasteren*. Sint Lucas Andreas Ziekenhuis, Amsterdam: Dr. J. Veenstra*, Dr. K.D. Lettinga. Slotervaartziekenhuis, Amsterdam: Dr. J.W. Mulder*, Drs. S.M.E. Vrouenraets, Dr. F.N. Lauw. Stichting Medisch Centrum Jan van Goyen, Amsterdam: Drs. A. van Eeden*, Dr. D.W.M. Verhagen. Universitair Medisch Centrum Groningen, Groningen: Drs. H.G. Sprenger*, Drs. R. Doedens, Dr. E.H. Scholvinck, Dr. S. van Assen, Dr. W.F.W. Bierman. Universitair Medisch Centrum Sint Radboud, Nijmegen: Dr. P.P. Koopmans*, Dr. M. Keuter, Dr. A.J.A.M. van der Ven, Dr. H.J.M. ter Hofstede, Dr. A.S.M. Dofferhoff, Dr. A Warris, Dr. R. van Crevel. Universitair Medisch Centrum Utrecht, Utrecht: Prof. dr. A.I.M. Hoepelman*, Dr. T. Mudrikova, Dr. M.M.E. Schneider, Dr. P.M. Ellerbroek, Dr. J.J. Oosterheert, Dr. J.E. Arends, Dr. M.W.M. Wassenberg, Dr. R.E. Barth. Vrije Universiteit Amsterdam, Amsterdam: Dr. M.A. van Agtmael*, Dr. R.M. Perenboom, Drs. F.A.P. Claessen, Dr. M. Bomers, Dr. E.J.G. Peters. Wilhelmina Kinderziekenhuis, Utrecht: Dr. S.P.M. Geelen, Dr. T.F.W. Wolfs, Dr. L.J. Bont. Ziekenhuis Rijnstate, Arnhem: Dr. C. Richter*, Dr. J.P. van der Berg, Dr. E.H. Gisolf. Admiraal De Ruyter Ziekenhuis, Vlissingen: Drs. M. van den Berge*, Drs. A. Stegeman. Medisch Centrum Leeuwarden, Leeuwarden: Dr. M.G.A. van Vonderen*, Drs. D.P.F. van Houte. Medisch Centrum Zuiderzee, Lelystad: Dr. S. Weijer*, Dr. R. el Moussaoui. Sint Elisabeth Hospitaal, Willemstad - Curaçao: Dr. C. Winkel, Drs. F. Muskiet, Drs. Durand, Drs. R. Voigt. 14
15 New HIV diagnoses ~1100 new HIV diagnoses per year Two third of new diagnoses amongst MSM. Hardly any new infections due to injection drug use.
16 Region of origin MSM Heterosexuals
17 Age at diagnosis Increasing number of new diagnoses in young MSM and older MSM and heterosexuals. 37% of those in care 50 years or older.
18 Face-to-Face HIV Intercohorts Meeting Rome, November 22-23, 2013 Caroline Sabin, UCL
19 The new naives
20 The new naives
21 UK CHIC characteristics of patients at entry to study n % Total number of patients Sex: Female Risk group: Homo/bisexual IDU Heterosexual Other/not known Ethnicity: White Black African Other Not known Median (IQR) age at first entry into cohort (years): UK CHIC 2012 dataset
22 The new naives - questions BHIVA guidelines now permit cart for asymptomatic persons with CD4 count >350 cells/mm 3 if patient wishes to take TasP - those who remain untreated, therefore, reflect an increasingly selected subset of the HIV+ve population What biases does this introduce? Is it ever possible to study questions relating to natural history? What will happen to datasets (and generalisability) if (noncomplex) HIV care is increasingly transferred to primary care? Will we ever be able to make comparisons of cart outcomes in those starting cart at different CD4 counts?
23 Hansjakob Furrer
24 New Naives African women 45% of all women European MSM Less IDU Recency of infection recent old
25 New Naives Age agereg HET IDU MSM agereg HET IDU agereg WE SSA
26 New Naives Use resistance (pol squences) data for epidemiology Transmission networks Kouyos, CID 2010 Recency of infection ambiguous nucleotides in partial pol sequences Kouyos, CID 2011 ambigouos HET/IDU MSM
27 Trends overtime of late presenters (with cut-offs of 350 and 500)
28 Face-to-face Intercohorts meeting Rome Ard van Sighem Rome, 22 November 2013
29 Late presenters late-stage advanced stage Late Advanced Overall 43% 26% MSM 37% 19% Heterosexual men 64% 44% Heterosexual women 55% 35% 29
30 Recent infections Increasing proportion of recent infections in MSM. Higher proportion of recent infection in young adults.
31 Changes in CD4 at start cart
32 Face-to-Face HIV Intercohorts Meeting Rome, November 22-23, 2013 Caroline Sabin, UCL
33 Late presentation, E&W, 2011 HIV and AIDS Reporting System, Public Health England, 2011
34 Trends over time, late presentation, E&W HIV and AIDS Reporting System, Public Health England, 2011
35 Late presentation - questions Are all late presenters really late presenters? - How many have been seen previously at non-uk CHIC clinics? - How do we identify these patients? Are cart outcomes in late presenters still poorer than those in non-late presenters? - If so, is this due to late presentation or does it reflect the lifestyles and personalities of those who present late? Are trends similar in all exposure groups and in all geographical locations? Do late presenters starting modern cart regimens continue to place a financial burden on healthcare systems, even after being on cart for some time?
36 Hansjakob Furrer
37 Late presenter Wandeler, Hachfeld, Furrer submitted to CROI 2014 CD4 < 350 or ADI within 3 mo (n=1366) 52% late presenters 48% CD4 < % AIDS defining illness 27% CD4 < 200 Risk: SSA female low education level cd4_first_val ,000 excludes outside values
38 Late Presenters, Trend cd4_first_val ,000 P<0.001 P=0.1 01_04 05_08 09_12 excludes outside values
39 First Round Table: Epidemiology: the new naïve, new epidemiological trends
40 Q2: trends over time of late presenters (with cut-offs of 350 and 500) Definition of late presenters CD4<200 and/or AIDS CD4<350 and/or AIDS CD4<500 and/or AIDS difficult to evaluate trends over time at present EuroSIDA
41 Proportion of EuroSIDA patients starting cart at various CD4-cell strata and presence of AIDS diagnosis CD4 < 200 or AIDS CD4 = CD4 >= 350 Missing CD4 and no AIDS % <= >=2007 <= >=2007 <= >=2007 Year started cart <= >=2007 <= >=2007 <= >=2007 SE WCE NE ECE EE AR N: EuroSIDA Podlekareva, BMC Inf Dis 2012
42 100 Late Presentation Advanced Disease AIDS CD4 Late presentation over calendar time COHERE Crude odds ratio 0.96 ( ) per calendar year IMIT AMACS ECS-Mothers & ECS-Infants NSHPC-Mothers & NHPS-Infants PISCIS KOMPNET CASCADE ANRS CO2 SEROCO Frankfurt HIV Cohort Study San Raffaele ANRS CO1/CO10 EPF UK CHIC Athena ITLR-Mothers & ITLR-Infants Swiss HIV Cohort Study ICC ANRS CO6 PRIMO Co-RIS MOCHIV-Mothers & MoCHIV-Infants The Italian MASTER Cohort CHIPS ANRS CO4 French Hospital s Database on HIV HIV-MIP-Mothers & HIV-MIP-Infants GEMES-Haemo ANRS CO3 AQUITAINE EuroSIDA Madrid Cohort HIV Children VACH Modena Cohort Study Danish HIV Study ANRS CO8 COPILOTE ICONA St. Pierre Collaboration of Observational HIV Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED) 400 Proportion Median CD4 at presentation /11 Year of presentation N Late presentation : CD4 < 350/AIDS; advanced disease : CD4<200/AIDS 0 EuroSIDA Mocroft, PLoS Medicine 2013
43 100 Late Presentation Advanced Disease AIDS CD4 Late presentation over calendar time COHERE Crude odds ratio 0.96 ( ) per calendar year IMIT AMACS ECS-Mothers & ECS-Infants NSHPC-Mothers & NHPS-Infants PISCIS KOMPNET CASCADE ANRS CO2 SEROCO Frankfurt HIV Cohort Study San Raffaele ANRS CO1/CO10 EPF UK CHIC Athena ITLR-Mothers & ITLR-Infants Swiss HIV Cohort Study ICC ANRS CO6 PRIMO Co-RIS MOCHIV-Mothers & MoCHIV-Infants The Italian MASTER Cohort CHIPS ANRS CO4 French Hospital s Database on HIV HIV-MIP-Mothers & HIV-MIP-Infants GEMES-Haemo ANRS CO3 AQUITAINE EuroSIDA Madrid Cohort HIV Children VACH Modena Cohort Study Danish HIV Study ANRS CO8 COPILOTE ICONA St. Pierre Collaboration of Observational HIV Epidemiological Research Europe Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED) 400 Proportion Median CD4 at presentation ( : 306 ->363 /mm 3 ): 333 (IQR: )/mm 3 ~75% presenting with a CD4<500/mm Median CD4 at presentation /11 Year of presentation N Late presentation : CD4 < 350/AIDS; advanced disease : CD4<200/AIDS 0 EuroSIDA Mocroft, PLoS Medicine 2013
44 Factors associated with late presentation: Older age: aor: 1.41/10 y older; 95% CI Region of origin: aor (Africa v. Europe): 1.75; 95% CI aor (other regions v. Europe): 1.40; 95% CI Region of follow-up : aor (Southern v. Central Europe): 1.41; 95% CI All HIV-exposure groups compared to MSM Delayed entry into care: aor: 0.91; 95% CI More recent calendar year: aor (per later calendar year): 0.96; 95% CI EuroSIDA
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