Among the 1042 deaths reported by 168 wards, 889 were identified by 117 wards that also participated in 2000 survey. The distribution of causes of death reported in 2005 by the wards that participated in the 2 surveys (2000 and 2005) was similar to the overall distribution. The 153 cases documented and reported by new participating wards were more frequently related to AIDS (39% vs 36%), to non-AIDS non-hepatitis-related cancers (24% vs 15%), and to liver disease (17% vs 14%), and less frequently related to cardiovascular disease (4% vs 9%) (P = 0.006).
Among 94 individuals who died within 6 months of HIV diagnosis, the diagnosis of HIV was done before death, the most frequent cause of death was AIDS (76%) and the most frequent AIDS-defining illnesses were Pneumocystis jiroveci pneumonia (27%), NHL (21%), and PML (20%) (Fig. 2).
Taking into account gender and age, the frequency of the 5 main underlying causes of death differed significantly between 2000 and 2005 (P = 0.001). These changes differed according to age (Table 2). Below 30 years, 2 in 3 deaths were AIDS related in both 2000 and 2005. The proportion of AIDS-related deaths decreased mainly above 40 years, from half in 2000 to 1 in 3 cases in 2005. From 2000 to 2005, the proportion of liver-related deaths decreased in the 30-40 years' age strata and increased from 15% to 20% in the 40-50 years' age strata. The increase in the proportion of cancer-related deaths was higher when age was higher. The increase in the proportion of cardiovascular-related deaths was moderate and mainly in the 40-50 years' age strata.
The proportion of cardiovascular-related deaths only slightly increased. Improvement of antiretroviral strategies and management of dyslipidemia may have slowed an initially worse trend.12 Nevertheless, the relative contribution of HIV infection, antiretrovirals, and traditional risk factors in the occurrence of metabolic-related diseases is still debated.37
Although our observations have been made in the French context of free access to care, we believe that some characteristics of deceased patients reflect suboptimal management. The proportion of patients who died within 6 months of HIV diagnosis (9%) remained stable between 2000 and 2005. In London between 1998 and 2003, around one-fifth of all deaths occurred among individuals who had first been diagnosed with HIV within the 6 months before death.10 In France, more than 1 in 3 patients attending HIV care for the first time have advanced HIV infection,38 and delayed access to care was more frequent in migrants, as reported in other settings.39 In addition, 1 in 3 HIV-infected adults who died in 2005 was in poor socioeconomic conditions. The association between socioeconomic conditions and premature mortality is a constant in the general population40 and applies to HIV-infected populations.41
Over time, the latest CD4 cell count before death increased, as also reported by others.9 Nevertheless, despite 81% of our series had received cART, latest CD4 cell count was less than 200/mm3 among half of them. Median latest CD4 cell count was lower in people who died of AIDS and was around 200/mm3 in those who died of non-AIDS non-hepatitis-related cancers and of ESLD. Recent communications underlined that the risk of serious non-AIDS-defining events is higher with lower CD4 cell counts,42-44 and mortality rates in treated HIV-infected adults may reach those of the general population in the long term only when CD4 cell counts are above 500/mm3.45 Even if they are mostly treated, patients still experience immunodeficiency. In 2005, median CD4 cell count of patients followed in the French hospital database on HIV (n = 48,410) was 443/mm3 and 11% had CD4 less than 200/mm3.46
A larger number of wards participated in the current study compared with 2000. Nevertheless, we compared the distribution of causes of death regardless of participating wards. The overall distribution of the underlying causes of death in 2005 did not differ in the subgroup of wards that participated in the 2 surveys. Therefore, selecting only these wards would not have changed the results. Wards that participated in the Mortalité 2005 survey represented around 78,000 HIV-infected patients, whereas based on currently available data,47-49 we may consider that 100,000 individuals were living with HIV in France in 2005.
Few surveys like Mortalité 2000 and Mortalité 2005 are specifically implemented to analyze the causes of death in HIV-infected individuals. This survey is based on specific declarations of physicians and active monitoring and has advantages over existing observational cohorts. First, it may be more representative of the population of HIV-infected patients who died than studies of the causes of death in observational cohorts, which may select the patients under follow-up. Second, the determination of causes of death is based on detailed and standardized documentation that is rarely available in cohorts.
Given the confirmed emergence of heterogeneous causes of death and their link with specific characteristics of patients, surveillance of the causes of death over time among HIV-infected individuals across different geographical areas is important to adapt recommendations to specific context. In addition, it seems highly desirable to implement collection of all causes of severe morbidity in existing observational studies on HIV to allow earlier interventions in HIV case management. Indeed, there is still a potential to improve antiretroviral management in HIV-infected individuals because AIDS-related deaths still occur. Prevention and early detection of serious morbidity may include improved strategies to diagnose HIV infection earlier, particularly in migrants and people with poor socioeconomic conditions; maintaining efforts to reach high levels of CD4 cell count to prevent both persistent AIDS and non-AIDS-defining events related to immune suppression and including a proactive identification of obstacles to optimal response to treatment; implementing active prevention of the most frequent cancers, particularly through the promotion of smoking cessation programs; evaluating the benefits of targeted screening of cancers in patients at risk; improving HCV treatment coverage and efficacy; and improving prevention and management of diabetes and dyslipidemia to limit the occurrence of cardiovascular disease. The implementation of these recommendations will be especially important in the context of an aging HIV-infected population.
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-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy
: aquitaine cohort, France. Clin Infect Dis
23. CASCADE Collaboration. Changes over calendar time in the risk of specific first AIDS
-defining events following HIV seroconversion, adjusting for competing risks. Int J Epidemiol
24. CASCADE Collaboration. Systemic non-Hodgkin lymphoma in individuals with known dates of HIV seroconversion: incidence and predictors. AIDS
25. Clifford GM, Polesel J, Rickenbach M, et al. Cancer
risk in the Swiss HIV cohort study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy
. J Natl Cancer Inst
26. Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer
risk among people with AIDS
in the United States 1980-2002. AIDS
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-related systemic non-Hodgkin lymphoma treated with chemotherapy and highly active antiretroviral therapy
depends exclusively on tumor-related factors. J Acquir Immune Defic Syndr
28. Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS
-defining cancers before and during the highly active antiretroviral therapy
era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol
29. Bénard A, Tessier J-F, Rambeloarisoa J, et al. HIV infection and tobacco smoking behaviour: prospects for prevention? ANRS CO 3 Aquitaine Cohort, 2002. Int J Tuberc Lung Dis
30. Friis-Møller N, Weber R, Reiss P, et al. Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy
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APPENDIX: MORTALITÉ 2005 (ANRS EN19) GROUP, IN COLLABORATION WITH MORTAVIC
The following are available at: http://etudes.isped.u-bordeaux2.fr/M2005/TELECHARGTS/M2005_GroupeEtude.pdf.
Geneviève Chêne, Dominique Costagliola, Eric Jougla, Thierry May, Philippe Morlat, Dominique Salmon, Patrice Cacoub, Eric Rosenthal, Fabrice Bonnet, Christine Burty, Charlotte Lewden.
Coding, Monitoring Data Management, and Analysis
Muriel François, Jean Boileau, Hélène Zouari, Fabien Tourteau, Vincent Bouteloup.
P. Bursacchi, J. F. Delfraissy (ANRS), C. Semaille (InVS).
Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS; CSS5).
CMIT(Collège des Universitaires de Maladies infectieuses et Tropicales), SFLS (Société Française de Lutte contre le Sida), SNFMI (Société Nationale Française de Médecine Interne), SPILF (Société de Pathologie Infectieuse de Langue Française), ADELF (Association des Epidémiologistes de Langue Française), GERMIVIC (Groupe d'Etude et de Recherche en Médecine Interne et Maladies Infectieuses sur le VIrus de l'hépatite), FPRRH (Fédération des Pôles de Références et Réseaux Hépatites), AFEF (Association Française Etude du Foie), SRLF (Société de Réanimation de langue Française), SPLF (Société de Pneumologie de Langue Française).
List of Participants
The following are available at: http://etudes.isped.u-bordeaux2.fr/M2005/TELECHARGTS/M2005_ListeParticipants.pdf
Abbeville S. Redecker/Agen Y. Imbert P. Rispal/Aix En Provence T. Allègre J. Riou M. Marquant/P. Undreiner/Ajaccio J. Abino/Albi P. Barel/Greziller/Alencon Gosse/Ales A. Lagier D. Bastide/Amiens J. L. Schmit N. Decaux/Angers J. Chennebault P. Fialaire P. Abgueguen J. Loison/Annecy J. Gaillat/Annonay E. Legrand/Antibes Juan Les Pins J. Dor D. Quinsat L. Lerousseau Chavaillon E. Toquet-Maillet/Argenteuil L. Sutton P. Genet/Arles J. Salord/Arpajon G. Raison/Arras D. Dubois/Y. Lierman J. Bervar/Auch B. Castan/Aulnay Sous Bois D. Malbec J. Delassus/Auxerre R. Bakir/Avignon G. Lepeu G. Pichancourt A. Théodourou-Touchais/Olivier A. De La Blanchardière/Bar Le Duc P. Evon/Y. Aubry/Basse Terre B. Giffo/Bayonne F. Bonnal S. Labarrère/Bazas M. Amanieu/Beauvais D. Valet/Belfort J. P. Faller P. Eglinger F. Duchene/Besancon P. Humbert/J. Dupond/J. Estavoyer B. Hoen C. Roche C. Chirouze J. Faucher/Béziers E. Oziol A. Saad M. Cabrol/Blaye P. Gateau S. Seiberras/Blois C. Vidal/A. Mazari/Bobigny M. Bentata P. Honore/O. Bouchaud/Bois Guillaume C. Bessin/Bondy V. Jeantils S. Tassi/O. Fain/Bordeaux M. Dupon/P. Morlat J. Beylot D. Lacoste M. Bonarek N. Bernard F. Bonnet/J. M. Ragnaud/M. Longy-Boursier P. Mercié/C. Séries/Bordeaux Armées B. Portal F. Terrier/Boulogne E. Rouveix C. Olivier/J. Vaillant/Boulogne Billancourt S. Moulias/T. Hanslik/Bourg En Bresse P. Granier/T. Colucci/Bourges M. Mornet/L. Aaron Y. Guimard J. Agbodjan J. Julien/Bourgoin Jallieu M. Fabre/Brest M. Garre/Gouerou O. Savary J. Nousbaum/Brest Armées H. Granier/Briançon P. Brousse/Caen R. Verdon P. Féret/Guivarch/ Cahors S. Sire/Cannes P. Simonet S. Tempesta B. Vialatte/Castres L. Prudhomme/Cayenne F. Djossou S. Bichat M. Nacher P. Couppié/Chalon Sur Saône Dellinger/Chalons En Champagne J. Picard/Sabbagh/Chambery O. Rogeaux/Charleville Mézières C. Penalba/Chartres C. Aubert/Chaumont C. Alba/ Clamart P. Galanaud F. Boué/G. Defuentes/Clermont De L'oise J. Pik/Clermont-Ferrand H. Laurichesse J. Beytout L. Cormerais/Clichy B. Fantin A. Uludag/J. Mantz J. Cohen/Colmar F. Kohser/N. Plaisance G. Blaison M. Martinot/Colombes C. Minozzi C. Ferreira F. Zeng/Compiègne Y. Domart D. Merrien D. Zylberait/Corbeil-Essonnes A. Devidas I. Turpauld P. Chevojon/Coulommiers M. Bardet/Coutances P. Jacquemard/Créteil A. Sobel C. Jung C. Dumont/M. Chousterman/B. Housset L. Bassinet/F. Schortgen/Dax P. Loste/Désertine O. Antoniotti E. Nehme/Digne Les Bains P. Granet Brunello/Dijon H. Portier M. Grappin M. Buisson M. Duong C. Braconnier A. Waldner-Combernoux/Dinan J. Laine/Dole A. Brousse/Douai G. Cardon/F. Visticot/Draguignan M. Vella/ Dunkerque F. Bonnevie/Vanrenterghem/Eaubonne T. Soupison/N. Gruat/J. Roche Sicot J. Saraux A. Leprêtre L. El Hajj/Ecrouves Frossard/ Elbeuf M. Brung Lefebvre/Epinal I. Béguinot H. Schuhmacher/Etampes J. Hirsch/Evreux/G. Reumont/Saad/Eysses Galan/Foix Estebe/Fort De France A. Cabié S. Abel/D. Quist/Frejus E. Counillon R. Armero P. Del Giudice/Frelinghien V. Gamblin/Fresnes I. Bouchard/Garches P. De Truchis H. Berthe/Grenoble P. Leclercq C. Brambilla E. Gineste F. Sarrot-Reynauld/Jenny/Ingwiller J. Class/Ivry Sur Seine A. Raynaud-Simon/Kourou F. Alvarez/La Roche Sur Yon P. Perre O. Aubry I. Suaud/La Rochelle I. Courbes B. Batejat/La Teste De Buch A. Dupont/Lagny Sur Marne P. Lagarde F. David-Ouaknine/Landerneau E. Le Moigne/Langon B. Caumont/Laon M. Robin/Laval J. Hoel/Le Chesnay J. Doll P. Colardelle S. Roussin-Bretagne/A. Greder Belan/J. Bedos F. Bruneel/Le Grand Luce F. Thibous Lemeunier/Le Kremlin Bicêtre J. Delfraissy C. Goujard M. Rannou/Le Port P. Wind/Le Puy En Velay B. Monange/Lens C. Lamblin K. Cochonat/M. Balquet/Levallois Perret D. Champetier De Ribes G. Force/Libourne J. Ceccaldi/J. Marcos/Lille Y. Hammou/X. Codaccioni/Limoges P. Weinbreck C. Genet/M. Debette-Gratien/Lisieux L. Geffray/Longjumeau Y. Le Mercier/Longuenesse Follet/Lons Le Saunier B. Duvert/Lacroix/Loudun A. Arnaud/Lure Y. Selles/F. Levasseur/Lyon J. Touraine F. Jeanblanc/C. Trepo N. Benmakhlouf B. Lebouche/D. Peyramond A. Boibieux C. Chidiac C. Delorme/E. Carbonnel/V. Baty/Macon J. Kisterman X. Roubert/Mantes La Jolie F. Granier F. Trémolières C. Billy V. Perronne/Marmande J. Testaud/Marseille J. Gastaut M. Drogoul G. Fabre/A. Stein H. Gallais I. Ravaux/J. Moreau E. Vandergheynst/M. Bourlière/J. Ruiz/P. Philibert/T. Gamby/N. Petit/Marseille Armées F. Simon/Maubeuge Fontaneau/Mende P. Meissonnier/Menton J. Bayada/Metz B. Christian A. Armand/Metz Armées M. Galzin/Millau D. Dumas/Mont De Marsan S. De Witte/Montbéliard J. Jobard/Montélimar A. Poncet/B. Caillet/Montpellier J. Reynes C. Merle De Boever M. Siffert A. Bourgeois A. Villadoro C. Tramoni/V. Faucherre/D. Larrey/O. Jonquet Landreau/Montreuil M. Andre C. Winter/Morlaix C. Roge/Mulhouse G. Beck-Wirth B. Drenou M. Benomar/Nanterre M. Ruel K. Chemlal/Nantes F. Raffi P. Morineau-Le Houssine C. Guerbois Le Bavec/F. Lemesre/Narbonne B. Masson/Nemours F. Loison M. Razafimahery/Nevers J. Lebas De Lacour/Nice P. Dellamonica V. Mondain-Miton E. Cua N. Oran L. Valério/E. Rosenthal J. Fuzibet/A. Tran/P. Brocker/P. Barrelier/Nimes D. Vincent J. Mauboussin C. Barbuat I. Rouanet/N. Jourdan/A. Sotto F. Del Bucchia J. Jourdan/Niort M. Lapine/Nouméa P. Capdevielle/F. Lacassin-Beller F. Droetto/Noyon G. Diab F. Grihon/Orléans P. Arsac/L. Hocqueloux/Orsay M. Levasseur/Paimpol M. Fourdilis/Papeete P. Jarno/Paris J. Derouineau/P. Morel F. Timsit/A. Compagnucci/E. Oksenhendler L. Gérard J. Delgado/D. Sereni C. Lascoux-Combe/J. Viard B. Dupont A. Maignan/J. Bergmann P. Sellier J. Magnier/G. Pialoux V. Godard A. Goetschel M. Lebrette/L. Weiss D. Tisné-Dessus/C. Leport J. Ecobichon U. Colasante/L. Guillevin D. Salmon-Ceron M. Piétri A. Brunet B. Silbermann P. Blanche/H. Schoen M. Valantin P. Hausfater V. Martinez/S. Herson A. Simon C. Brancon/P. M. Girard A. Béglé G. Raguin C. Lupin/J. M. Molina D. Ponscarme V. Garrait P. Cabotin M. Janier E. Spindler/P. Yéni J Gerbe/J. Cabane/J. Ziza J. Aerts/J. Carlet J. Gilquin I. Auperin B. Misset A. Crof/J. Piette P. Cacoub/G. Turpin/B. Varet/N. Dupin/C. Le Jeunne E. Aslangul/S. Pol/T. Poynard P. Lebray/N. Carbonell/P. Benlian/M. Goujon/J. Dhainaut J. Charpentier/J. Andrieu/M. Brunel/N. Landgraf/M. Bary/Pau Pouyanne/Périgueux J. Méraud/C. Rivière/Perpignan H. Aumaître M. Saada/H. Cros/Pessac J. L. Pellegrin R. Adjeoda/Pierre Benite I. Durieu H. Rousset D. Vital-Durand/Pointe A. Pitre I. Lamaury M. Sow/Poissy D. Hillion H. Masson/Poitiers B. Becq-Giraudon G. Le Moal/C. Silvain/Pontoise O. Danne L. Blum/Quimper J. Larzul P. Perfezou/Reims C. Rouger/J. Novella/Rennes C. Michelet P. Tattevin C. Arvieux F. Souala M. Delmont-Hanry D. Guyader/V. Gandemer/C. Camus/Taverson/Roanne M. Lutz/Rochefort M. Climas/Roubaix J. Wemeau/Rouen I. Gueit P. Suel/F. Caron/Saint Denis D. Mechali M. Khuong-Josses/Saint Die Des Vosges Y. Etienne/Saint Etienne F. Lucht A. Fresard V. Ronat/Vergnon/Garcier/Saint Girons J. Deluca/Saint Laurent Du Maroni A. Randrianjohany/Saint Omer H. Monnot/Saint Pierre De La Réunion P. Poubeau H. Andre/Saint-Brieuc C. Beuscart/M. Aubry/Saint-Denis E. Hurbin/Saint-Mandé T. Debord C. Rapp/Saint-Martin F. Bissuel V. Walter/Saint-Martin-De-Ré J. Ferret/ Saint-Michel M. Bonnefoy A. Riche/Saint-Nazaire J. Marot C. Michau/Saintes E. Bonnin/T. Pasdeloup/Salouel G. Chaby/Sarrebourg E. Grilliat/Saverne E. Wurtz/F. Loth/Sete B. Kitschke/Soissons D. Line/St Denis De La Réunion C. Gaud C. Sautron/St Etienne P. Cathebras/St Germain En Laye Y. Welker/St Nazaire D. Sandron/Strasbourg J. M. Lang P. Fischer/J. Pasquali H. Lalanne/C. Chartier/C. Berlin/E. Andres/D. Christmann Y. Hansmann/P. Fraisse/Suresnes O. Bletry D. Zucman C. Majerholc/M. Stern L. Couderc/Tarbes J. Petitou/Thionville F. Truchetet J. Pouaha/Thonon Les Bains P. Romand/Toulon A. Lafeuillade V. Lambry/Toulon Naval P. Bernard/Toulouse D. Adoue M. Duffaut/B. Marchou D. Garipuy L. Cuzin/M. Uzan/J. Vinel S. Metivier/A. Didier R. Rouquet/Tourcoing Y. Mouton Y. Yazdanpanah F. Marysse/B. Guery K Faure/Tours J. M. Besnier P. Le Bret P. Nau H. Sigogneau/Troyes J. Bressieux E. Libbrecht L. Rezzouk/Tulle A. Collignon/Valence B. Ponceau/Valenciennes X. Kyndt/A. Vermersch-Langlin/Vandoeuvre Les Nancy T. May C. Burty/P. Lederlin/Vannes Y. Poinsignon/Verdun C. Creusat/Vernon C. Richard/Vesoul C. Merle/Vierzon A. Essayan/Villejuif D. Vittecoq C. Bolliot/Villenauxe-La-Grande Quignard/Villeneuve St Georges O. Patey S. Dellion/Villeneuve/Lot I. Chossat.