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Clin Infect Dis. 2009 Apr 15;48(8):1138-51. doi: 10.1086/597468.

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

Collaborators (855)

Casabona J, Chêne G, Costagliola D, Dabis F, D'Arminio Monforte A, de Wolf F, Egger M, Fatkenheuer G, Gill J, Hogg R, Justice A, Kitahata M, Ledergerber B, Mocroft A, Phillips A, Reiss P, Saag M, Sabin C, Staszewski S, Weller I, May M, Harris R, Sterne J, Abgrall S, Barin F, Bentata M, Billaud E, Boué F, Burty C, Cabié A, Cotte L, De Truchis P, Duval X, Duvivier C, Enel P, Fredouille-Heripret L, Gasnault J, Gaud C, Gilquin J, Grabar S, Katlama C, Khuong MA, Lang JM, Lascaux AS, Launay O, Mahamat A, Mary-Krause M, Matheron S, Meynard JL, Pavie J, Pialoux G, Pilorgé F, Poizot-Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tattevin P, Tissot-Dupont H, Viard JP, Viget N, Pariente-Khayat A, Salomon V, Jacquemet N, Rivet A, Guiguet M, Kousignian I, Lanoy E, Lièvre L, Potard V, Selinger-Leneman H, Bouvet E, Crickx B, Ecobichon JL, Leport C, Picard-Dahan C, Yeni P, Tisne-Dessus D, Weiss L, Salmon D, Sicard D, Auperin I, Roudière L, Fior R, Delfraissy JF, Goujard C, Jung C, Lesprit P, Desplanque N, Meyohas MC, Picard O, Cadranel J, Mayaud C, Bricaire F, Herson S, Clauvel JP, Decazes JM, Gerard L, Molina JM, Diemer M, Sellier P, Berthé H, Dupont C, Chandemerle C, Mortier E, Honoré P, Jeantils V, Tassi S, Mechali D, Taverne B, Gourdon F, Laurichesse H, Fresard A, Lucht F, Eglinger P, Faller JP, Bazin C, Verdon R, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Trepo C, Ravaux I, Delmont JP, Moreau J, Gastaut JA, Retornaz F, Soubeyrand J, Allegre T, Blanc PA, Galinier A, Ruiz JM, Lepeu G, Granet-Brunello P, Esterni JP, Pelissier L, Cohen-Valensi R, Nezri M, Chadapaud S, Laffeuillade A, May T, Rabaud C, Raffi F, Arvieux C, Michelet C, Borsa-Lebas F, Caron F, Fraisse P, Rey D, Arlet-Suau E, Cuzin L, Massip P, Thiercelin Legrand MF, Yasdanpanah Y, Pradinaud R, Sobesky M, Contant M, Montroni M, Scalise G, Braschi MC, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Arici C, Chiodo F, Colangeli V, Fiorini C, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Manconi PE, Piano P, Cosco L, Scerbo A, Vecchiet J, D'Alessandro M, Santoro D, Pusterla L, Carnevale G, Lorenzotti S, Viganò P, Mena M, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Lo Caputo S, Grisorio B, Ferrara S, Grima P, Grima PF, Pagano G, Cassola G, Alessandrini A, Piscopo R, Toti M, Trezzi M, Soscia F, Tacconi L, Orani A, Perini P, Scasso A, Vincenti A, Chiodera F, Castelli P, Scalzini A, Palvarini L, Moroni M, Lazzarin A, Rizzardini G, Caggese L, Cicconi P, Galli A, Merli S, Pastecchia C, Moioli MC, Esposito R, Mussini C, Abrescia N, Chirianni A, Izzo CM, Piazza M, De Marco M, Viglietti R, Manzillo E, Nappa S, Colomba A, Abbadessa V, Prestileo T, Mancuso S, Ferrari C, Pizzaferri P, Filice G, Minoli L, Bruno R, Novati S, Baldelli F, Camanni G, Petrelli E, Cioppi A, Alberici F, Ruggieri A, Menichetti F, Martinelli C, De Stefano C, La Gala A, Ballardini G, Rizzo E, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Dianzani F, Ippolito G, Antinori A, Antonucci G, Ciardi M, Narciso P, Petrosillo N, Vullo V, De Luca A, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Noto P, Lichtner M, Capobianchi MR, Carletti F, Girardi E, Pezzotti P, Rezza G, Mura MS, Mannazzu M, Caramello P, Di Perri G, Orofino GC, Sciandra M, Grossi PA, Basilico C, Poggio A, Bottari G, Raise E, Ebo F, Pellizzer G, Buonfrate D, Resta F, Loso K, Cozzi Lepri A, Battegay M, Bernasconi E, Böni J, Bucher H, Bürgisser P, Cattacin S, Cavassini M, Dubs R, Elzi L, Erb P, Fischer M, Flepp M, Fontana A, Francioli P, Furrer H, Gorgievski M, Günthard H, Hirsch H, Hirschel B, Hösli I, Kahlert C, Kaiser L, Karrer U, Kind C, Klimkait T, Martinetti G, Martinez B, Müller N, Nadal D, Opravil M, Paccaud F, Pantaleo G, Rickenbach M, Rudin C, Schmid P, Schultze D, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S, Gras LA, van Sighem AI, Smit C, Bronsveld W, Hillebrand-Haverkort ME, Prins JM, Branger J, Eeftinck Schattenkerk JK, Gisolf J, Godfried MH, Lange JM, Lettinga KD, van der Meer JT, Nellen FJ, van der Poll T, Ruys TA, Steingrover R, Vermeulen JN, Vrouenraets SM, van Vugt M, Wit FW, Kuijpers TW, Pajkrt D, Scherpbier HJ, van Eeden A, Brinkman K, van den Berk GE, Blok WL, Frissen PH, Roos JC, Schouten WE, Mulder JW, van Gorp EC, Wagenaar J, Veenstra J, Danner SA, Van Agtmael MA, Claessen FA, Perenboom RM, Rijkeboer A, van Vonderen MG, Richter C, van der Berg J, Vriesendorp R, Jeurissen FJ, Kauffmann RH, Pogány K, Bravenboer B, ten Napel CH, Kootstra GJ, Sprenger HG, van Assen S, van Leeuwen JT, Doedens R, Scholvinck EH, ten Kate RW, Soetekouw R, van Houte D, Polée MB, Kroon FP, van den Broek PJ, van Dissel JT, Schippers EF, Schreij G, van der Geest S, Lowe S, Verbon A, Koopmans PP, Van Crevel R, de Groot R, Keuter M, Post F, van der Ven AJ, Warris A, van der Ende ME, Gyssens IC, van der Feltz M, Nouwen JL, Rijnders BJ, de Vries TE, Driessen G, van der Flier M, Hartwig NG, Juttman JR, van Kasteren ME, Van de Heul C, Hoepelman IM, Schneider MM, Bonten MJ, Borleffs JC, Ellerbroek PM, Jaspers CA, Mudrikove T, Schurink CA, Gisolf EH, Geelen SP, Wolfs TF, Faber T, Tanis AA, Groeneveld PH, den Hollander JG, Duits AJ, Winkel K, Back NK, Bakker ME, Berkhout B, Jurriaans S, Zaaijer HL, Cuijpers T, Rietra PJ, Roozendaal KJ, Pauw W, van Zanten AP, Smits PH, von Blomberg BM, Savelkoul P, Pettersson A, Swanink CM, Franck PF, Lampe AS, Jansen CL, Hendriks R, Benne CA, Veenendaal D, Storm H, Weel J, van Zeijl JH, Kroes AC, Claas HC, Bruggeman CA, Goossens VJ, Galama JM, Melchers WJ, Poort YA, Doornum GJ, Niesters MG, Osterhaus AD, Schutten M, Buiting AG, Swaans CA, Boucher CA, Schuurman R, Boel E, Jansz AF, Veldkamp A, Beijnen JH, Huitema AD, Burger DM, Hugen PW, van Kan HJ, Losso M, Duran A, Vetter N, Karpov I, Vassilenko A, Mitsura VM, Suetnov O, Clumeck N, De Wit S, Poll B, Colebunders R, Kostov K, Begovac J, Machala L, Rozsypal H, Sedlacek D, Nielsen J, Lundgren J, Benfield T, Kirk O, Gerstoft J, Katzenstein T, Hansen AB, Skinhøj P, Pedersen C, Oestergaard L, Zilmer K, Ristola M, Girard PM, Vanhems P, Rockstroh J, Schmidt R, van Lunzen J, Degen O, Stellbrink HJ, Bogner J, Kosmidis J, Gargalianos P, Xylomenos G, Perdios J, Panos G, Filandras A, Karabatsaki E, Sambattakou H, Banhegyi D, Mulcahy F, Yust I, Turner D, Burke M, Pollack S, Hassoun G, Maayan S, Chiesi A, Mazeu I, Pristera R, Gabbuti A, Montesarchio E, Gargiulo M, Iacomi F, Vlassi C, Finazzi R, Galli M, Ridolfo A, Rozentale B, Aldins P, Chaplinskas S, Hemmer R, Staub T, Bruun J, Maeland A, Ormaasen V, Knysz B, Gasiorowski J, Horban A, Prokopowicz D, Wiercinska-Drapalo A, Boron-Kaczmarska A, Pynka M, Beniowski M, Mularska E, Trocha H, Antunes F, Valadas E, Mansinho K, Maltez F, Duiculescu D, Rakhmanova A, Vinogradova E, Buzunova S, Jevtovic D, Mokrás M, Staneková D, González-Lahoz J, Soriano V, Martin-Carbonero L, Labarga P, Clotet B, Jou A, Conejero J, Tural C, Gatell JM, Miró JM, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Karlsson A, Persson PO, Flamholc L, Boffi E, Kravchenko E, Chentsova N, Barton S, Johnson AM, Mercey D, Johnson MA, Murphy M, Weber J, Scullard G, Fisher M, Brettle R, Gatell J, Gazzard B, Friis-Møller N, Bannister W, Ellefson M, Borch A, Podlekareva D, Holkmann Olsen C, Kjaer J, Peters L, Reekie J, Raffanti S, Dieterch D, Becker S, Scarsella A, Fusco G, Most B, Balu R, Rana R, Beckerman R, Ising T, Fusco J, Irek R, Johnson B, Hirani A, DeJesus E, Pierone G, Lackey P, Irek C, Johnson A, Burdick J, Leon S, Arch J, Helm EB, Carlebach A, Müller A, Haberl A, Nisius G, Lennemann T, Stephan C, Bickel M, Mösch M, Gute P, Locher L, Lutz T, Klauke S, Knecht G, Khaykin P, Doerr HW, Stürmer M, Babacan E, von Hentig N, Beylot J, Dupon M, Longy-Boursier M, Pellegrin JL, Ragnaud JM, Salamon R, Thiébaut R, Lewden C, Lawson-Ayayi S, Dupon M, Mercié P, Moreau JF, Morlat P, Bernard N, Lacoste D, Malvy D, Neau D, Blaizeau MJ, Decoin M, Delveaux S, Hannapier C, Labarrère S, Lavignolle-Aurillac V, Uwamaliya-Nziyumvira B, Palmer G, Touchard D, Balestre E, Alioum A, Jacqmin-Gadda H, Bonarek M, Bonnet F, Coadou B, Gellie P, Nouts C, Bocquentin F, Dutronc H, Lafarie S, Aslan A, Pistonne T, Thibaut P, Vatan R, Chambon D, De La Taille C, Cazorla C, Ocho A, Viallard JF, Caubet O, Cipriano C, Lazaro E, Couzigou P, Castera L, Fleury H, Lafon ME, Masquelier B, Pellegrin I, Breilh D, Blanco P, Loste P, Caunègre L, Bonnal F, Farbos S, Ferrand M, Ceccaldi J, Tchamgoué S, De Witte S, Buy E, Alexander C, Barrios R, Braitstein P, Brumme Z, Chan K, Cote H, Gataric N, Geller J, Guillemi S, Harrigan PR, Harris M, Joy R, Levy A, Montaner J, Montessori V, Palepu A, Phillips E, Phillips P, Press N, Tyndall M, Wood E, Yip B, Bhagani S, Breen R, Byrne P, Carroll A, Cuthbertson Z, Dunleavy A, Geretti AM, Heelan B, Johnson M, Kinloch-de Loes S, Lipman M, Madge S, Marshall N, Nair D, Nebbia G, Prinz B, Shah S, Swader L, Tyrer M, Youle M, Chaloner C, Grabowska H, Holloway J, Puradiredja J, Ransom D, Tsintas R, Bansi L, Fox Z, Harris E, Hill T, Lampe F, Lodwick R, Smith C, Amoah E, Booth C, Clewley G, Garcia Diaz A, Gregory B, Janossy G, Labbett W, Thomas M, Read R, Krentz H, Beckthold B, Schmeisser N, Alquézar A, Esteve A, Podzamczer D, Murillas J, Romero A, Agustí C, Agüero F, Ferrer E, Riera M, Segura F, Navarro G, Force L, Vilaró J, Masabeu A, García I, Guadarrama M, Montoliu A, Ortega N, Lazzari E, Puchol E, Sanchez M, Blanco JL, Garcia-Alcaide F, Martinez E, Mallolas J, López-Dieguez M, García-Goez JF, Sirera G, Romeu J, Negredo E, Miranda C, Capitan MC, Olmo M, Barragan P, Saumoy M, Bolao F, Cabellos C, Peña C, Sala M, Cervantes M, Jose Amengual M, Navarro M, Penelo E, Barrufet P, Raper JL, Mugavero MJ, Willig JH, Schumacher J, Chang PW, Westfall AO, Cloud G, Lin HY, Acosta EP, Colette-Kempf M, Allison JJ, Pisu M.

Abstract

BACKGROUND:

The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy.

METHODS:

We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category.

RESULTS:

During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]).

CONCLUSIONS:

In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

PMID:
19275498
PMCID:
PMC3032444
DOI:
10.1086/597468
[Indexed for MEDLINE]
Free PMC Article

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