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Ann Intern Med. 2011 Apr 19;154(8):509-15. doi: 10.7326/0003-4819-154-8-201104190-00001.

When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

Collaborators (1153)

Ainsworth J, Anderson J, Babiker A, Delpech V, Dunn D, Easterbrook P, Fisher M, Gazzard B, Gilson R, Gompels M, Hill T, Johnson M, Leen C, Orkin C, Phillips A, Pillay D, Porter K, Sabin C, Schwenk A, Walsh J, Bansi L, Hill T, Phillips A, Sabin C, Dunn D, Porter K, Glabay A, Orkin C, Thomas R, Jones K, Fisher M, Perry N, Pullin A, Churchill D, Gazzard B, Nelson M, Asboe D, Bulbeck S, Mandalia S, Clarke J, Delpech V, Anderson J, Munshi S, Post F, Easterbrook P, Khan Y, Patel P, Karim F, Duffell S, Gilson R, Man SL, Williams I, Gompels M, Dooley D, Schwenk A, Ainsworth J, Johnson M, Youle M, Lampe F, Smith C, Grabowska H, Chaloner C, Ismajani Puradiredja D, Bansi L, Hill T, Phillips A, Sabin C, Walsh J, Weber J, Kemble C, Mackie N, Winston A, Leen C, Wilson A, de Wolf F, Bezemer DO, Gras LA, Kesselring AM, van Sighem AI, Smit C, Zhang S, Zaheri S, Prins JM, Boer K, Bos JC, Geerlings SE, Godfried MH, Haverkort ME, Kuijpers TW, Lange JM, van der Meer JT, Nellen FJ, Pajkrt D, van der Poll T, Reiss P, Scherpbier HJ, van der Valk M, Vrouenraets SM, van Vugt M, Wit FW, Schreij G, Lowe S, Oude Lashof A, Bravenboer B, Pronk MJ, van der Ende ME, van der Feltz M, Gelinck LB, Nouwen JL, Rijnders BJ, de Ruiter ED, Slobbe L, Schurink CA, Verbon A, de Vries-Sluijs TE, Driessen G, Hartwig NG, Branger J, Kauffmann RH, Schippers EF, Groeneveld PH, Alleman MA, Bouwhuis JW, ten Kate RW, Soetekouw R, Kroon FP, Arend SM, de Boer MG, van den Broek PJ, van Dissel JT, Jolink H, van Nieuwkoop C, den Hollander JG, Pogany K, Bronsveld W, Kortmann W, van Twillert G, Vriesendorp R, Leyten EM, van Houte D, Polee MB, van Vonderen MG, ten Napel CH, Kootstra GJ, Brinkman K, van den Berk GE, Blok WL, Frissen PH, Schouten WE, van Eeden A, Verhagen DW, Mulder JW, van Gorp EC, Smit PM, Weijer S, Juttmann JR, Brouwer AE, van Kasteren ME, Veenstra J, Lettinga KD, Koopmans PP, Brouwer AM, Dofferhoff AS, van der Flier M, de Groot R, ter Hofstede HJ, Keuter M, van der Ven AJ, Sprenger HG, van Assen S, Doedens R, Scholvinck EH, Stek CJ, Hoepelman AI, Arends JE, Ellerbroek PM, van der Hilst JC, Jaspers CA, Maarschalk-Ellerbroek LJ, Oosterheert JJ, Peters EJ, Mudrikova T, Schneider MM, Wassenberg MW, Geelen SP, Wolfs TF, Danner SA, van Agtmael MA, Bierman WF, Claessen FA, de Jong EV, Kortmann W, Perenboom RM, bij de Vaate EA, Richter C, van der Berg J, Gisolf EH, van den Berge M, Stegeman A, Duits AJ, Winkel K, Abgrall S, Barin F, Bentata M, Billaud E, Boue F, Burty C, Cabie A, Costagliola D, 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, Pilorge F, Poizot-Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tattevin P, Tissot-Dupont H, Viard JP, Viget N, Salomon V, Jacquemet N, Abgrall S, Costagliola D, Grabar S, Guiguet M, Lanoy E, Lievre L, Mary-Krause M, Selinger-Leneman H, Lacombe JM, Potard V, Bricaire F, Herson S, Katlama C, Simon A, Desplanque N, Girard PM, Meynard JL, Meyohas MC, Picard O, Cadranel J, Mayaud C, Pialoux G, Clauvel JP, Decazes JM, Gerard L, Molina JM, Diemer M, Sellier P, Bentata M, Honore P, Jeantils V, Tassi S, Mechali D, Taverne B, Bouvet E, Crickx B, Ecobichon JL, Matheron S, Picard-Dahan C, Yeni P, Berthe H, Dupont C, Chandemerle C, Mortier E, de Truchis P, Tisne-Dessus D, Weiss L, Salmon D, Auperin I, Gilquin J, Roudiere L, Viard JP, Boue F, Fior R, Delfraissy JF, Goujard C, Jung C, Lesprit P, Vittecoq D, Fraisse P, Lang JM, Rey D, Beck-Wirth G, Stahl JP, Lecercq P, Gourdon F, Laurichesse H, Fresard A, Lucht F, Bazin C, Verdon R, Chavanet P, Arvieux C, Michelet C, Choutet P, Goudeau A, Maiotre MF, Hoen B, Eglinger P, Faller JP, Borsa-Lebas F, Caron F, Reynes J, Daures JP, May T, Rabaud C, Berger JL, Remy G, Arlet-Suau E, Cuzin L, Massip P, Thiercelin Legrand MF, Pontonnier G, Viget N, Yasdanpanah Y, Dellamonica P, Pradier C, Pugliese P, Aleksandrowicz K, Quinsat D, Ravaux I, Tissot-Dupont H, Delmont JP, Moreau J, Gastaut JA, Poizot-Martin I, Retornaz F, Soubeyrand J, Galinier A, Ruiz JM, Allegre T, Blanc PA, Bonnet-Montchardon D, Lepeu G, Granet-Brunello P, Esterni JP, Pelissier L, Cohen-Valensi R, Nezri M, Chadapaud S, Laffeuillade A, Billaud E, Raffi F, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Cotte L, Trepo C, Strobel M, Bissuel F, Pradinaud R, Sobesky M, Cabie A, Gaud C, Contant M, Aebi C, Battegay M, Bernasconi E, Boni J, Brazzola P, Bucher HC, Burgisser P, Calmy A, Cattacin S, Cavassini M, Cheseaux JJ, Drack G, Dubs R, Egger M, Elzi L, Fischer M, Flepp M, Fontana A, Francioli P, Furrer HJ, Fux C, Gayet-Ageron A, Gerber S, Gorgievski M, Gunthard H, Gyr T, Hirsch H, Hirschel B, Hosli I, Husler M, Kaiser L, Kahlert C, Karrer U, Kind C, Klimkait T, Ledergerber B, Martinetti G, Martinez B, Muller N, Nadal D, Paccaud F, Pantaleo G, Raio L, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schupbach J, Speck R, Taffe P, Telenti A, Trkola A, Vernazza P, Weber R, Wyler CA, Yerly S, Casabona J, Miro JM, Alquezar A, Isern V, Casabona J, Esteve A, Alquezar A, Miro JM, Podzamczer D, Murillas J, Gatell JM, Aguero F, Tural C, Clotet B, Ferrer E, Riera M, Segura F, Navarro G, Force L, Vilaro J, Masabeu A, Garcia I, Guadarrama M, Romero A, Agusti C, Esteve A, Montoliu A, Ortega N, Lazzari E, Puchol E, Sanchez M, Blanco JL, Garcia-Alcaide F, Martinez E, Mallolas J, Lopez-Dieguez M, Garcia-Goez JF, Sirera G, Romeu J, Jou A, Negredo E, Miranda C, Capitan MC, Olmo M, Barragan P, Saumoy M, Bolao F, Cabellos C, Pena C, Sala M, Cervantes M, Jose Amengual M, Navarro M, Penelo E, Barrufet P, Guadarrama M, Berenguer J, del Amo J, Garcia F, Gutierrez F, Labarga P, Moreno S, Munoz MA, Caro-Murillo AM, Sobrino P, Jarrin I, Gomez Sirvent JL, Rodriguez P, Aleman MR, Alonso MM, Lopez AM, Hernandez MI, Soriano V, Labarga P, Barreiro P, Medrano J, Rivas P, Herrero D, Blanco F, Vispo ME, Martin L, Ramirez G, de Diego M, Rubio R, Pulido F, Moreno V, Cepeda C, Hervas RL, Iribarren JA, Arrizabalaga J, Aramburu MJ, Camino X, Rodriguez-Arrondo F, von Wichmann MA, Pascual L, Goenaga MA, Gutierrez F, Masia M, Ramos JM, Padilla S, Sanchez-Hellin V, Bernal E, Escolano C, Montolio F, Peral Y, Berenguer J, Lopez JC, Miralles P, Cosin J, Sanchez M, Gutierrez I, Ramirez M, Padilla B, Vidal F, Sanjuan M, Peraire J, Veloso S, Vilades C, Lopez-Dupla M, Olona M, Vargas M, Aldeguer JL, Blanes M, Lacruz J, Salavert M, Montero M, Cuellar S, de los Santos I, Sanz J, Oteo JA, Blanco JR, Ibarra V, Metola L, Sanz M, Perez-Martinez L, Sola J, Uriz J, Castiello J, Reparaz J, Arriaza MJ, Irigoyen C, Moreno S, Antela A, Casado JL, Dronda F, Moreno A, Perez MJ, Lopez D, Gutierrez C, Hernandez B, Pumares M, Marti P, Garcia L, Page C, Garcia F, Hernandez J, Pena A, Munoz L, Parra J, Viciana P, Leal M, Lopez-Cortes LF, Trastoy M, Mata R, Justice AC, Fiellin DA, Mattocks K, Braithwaite S, Brandt C, Bryant K, Cook R, Conigliaro J, Crothers K, Chang J, Crystal S, Day N, Erdos J, Freiberg M, Kozal M, Gandhi N, Gaziano M, Gerschenson M, Good B, Gordon A, Goulet JL, Hernan MA, Kraemer K, Lim J, Maisto S, Miller P, Mole L, O'Connor P, Papas R, Robins JM, Rinaldo C, Roberts M, Samet J, Tierney B, Whittle J, Rimland D, Jones-Taylor C, Oursler KA, Titanji R, Brown S, Garrison S, Rodriguez-Barradas M, Masozera N, Goetz M, Leaf D, Simberkoff M, Blumenthal D, Leung J, Butt A, Hoffman E, Gibert C, Peck R, Phillips A, Babiker A, Brettle R, Darbyshire J, Delpech V, Easterbrook P, Fidler S, Fisher M, Gilson R, Goldberg D, Hawkins D, Jaffe H, Johnson A, Johnson M, McLean K, Pillay D, Porter K, Cursley A, Ewings F, Fairbrother K, Gnatiuc L, Lodi S, Murphy B, Smit E, Ward F, Douglas G, Kennedy N, Pritchard J, Andrady U, Rajda N, Maw R, McKernan S, Drake S, Gilleran G, White D, Ross J, Toomer S, Hewart R, Wilding H, Woodward R, Dean G, Heald L, Horner P, Glover S, Bansaal D, Eduards S, Carne C, Browing M, Das R, Stanley B, Estreich S, Magdy A, O'Mahony C, Fraser P, Hayman B, Jebakumar SP, Joshi U, Ralph S, Wade A, Mette R, Lalik J, Summerfield H, El-Dalil A, France AJ, White C, Robertson R, Gordon S, McMillan S, Morris S, Lean C, Morris S, Vithayathil K, McLean L, Winter A, Gale D, Jacobs S, Goorney B, Howard L, Tayal S, Short L, Roberts M, Green S, Williams G, Sivakumar K, Bhattacharyya DN, Monteiro E, Minton J, Dhar J, Nye F, DeSouza CB, Isaksen A, McDonald L, McLean K, Franca A, Hawkins D, William L, Jendrulek I, Peters B, Shaunak S, El-Gadi S, Easterbrook PJ, Mazhude C, Gilson R, Johnstone R, Fakoya A, Mchale J, Waters A, Kegg S, Mitchell S, Byrne P, Johnson M, Rice P, Fidler S, Mullaney SA, McCormack S, David D, Melville R, Phillip K, Balachandran T, Mabey S, Sukthankar A, Murphy C, Wilkins E, Ahmad S, Tayal S, Haynes J, Evans E, Ong E, Das R, Grey R, Meaden J, Bignell C, Loay D, Peacock K, Girgis MR, Morgan B, Palfreeman A, Wilcox J, Tobin J, Tucker L, Saeed AM, Chen F, Deheragada A, Williams O, Lacey H, Herman S, Kinghorn D, Devendra SV, Wither J, Dawson S, Rowen D, Harvey J, Wilkins E, Bridgwood A, Singh G, Chauhan M, Kellock D, Young S, Dannino S, Kathir Y, Rooney G, Currie J, Fitzgerald M, Devendra S, Keane F, Booth G, Green T, Arumainayyagam J, Chandramani S, Rajamanoharan S, Robinson T, Curless E, Gokhale R, Tariq A, Roberts M, Williams O, Luzzi G, FitzGerald M, Fairley I, Wallis F, Molina JM, Loze B, Sereni D, Lascoux C, Prevoteau F, Morel P, Timsit J, Oksenhendeler E, Gerard L, Morlat P, Bonarek M, Bonnet F, Nouts C, Louis I, Raffi F, Reliquet V, Sauser F, Biron C, Mounoury O, Hue H, Brosseau D, Delfraissy JF, Goujard C, Ghosn J, Rannou MT, Bergmann JF, Badsi E, Rami A, Diemer M, Parrinello M, Girard PM, Samanon-Bollens D, Campa P, Tourneur M, Desplanques N, Cabane J, Picard O, Tredup J, Desplanques N, Herriot E, Livrozet JM, Jeanblanc F, Chiarello P, Makhloufi D, Blanc AP, Allegre T, Reynes J, Baillat V, Lemoing V, Merle de Boever C, Tramoni C, Cabie A, Sobesky G, Abel S, Beaujolais V, Pialoux G, Slama L, Chakvetadze C, Berrebi V, Yeni P, Bouvet E, Fournier I, Gerbe J, Leport C, Jadand C, Jestin C, Longuet P, Boucherit S, Trepo C, Koffi K, Augustin-Normand C, Miailhes P, Thoirain V, Brochier C, Thomas R, Souala F, Ratajczak M, Montpied G, Beytoux J, Jacomet C, Gourdon F, Pare A, Rouveix E, Morelon S, Dupont C, Olivier C, Lortholary O, Dupont B, Viard JP, Maignan A, Ragnaud JM, Raymond I, Mondor H, Sobel A, Levy Y, Lelievre JD, Lascaux AS, Dominguez S, Dumont C, Aumaitre H, Delmas B, Saada M, Medus M, Guillevin L, Salmon D, Tahi T, Yazdanpanah Y, Pavel S, Marien MC, Muller E, Drenou B, Beck-Wirth G, Beck C, Benomar M, Katlama C, Tubiana R, Ait Mohand H, Chermak A, Ben Abdallah S, Herson S, Amirat N, Simon A, Brancion C, Bentata M, Touam F, Hoen B, Drobacheff C, Folzer A, Massip P, Obadia M, Prudhomme L, Bonnet E, Balzarin F, Pichard E, Chennebault JM, Fialaire P, Loison J, Galanaud P, Boue F, Bornarel D, Verdon R, Bazin C, Six M, Ferret P, Weiss L, Batisse D, Gonzales-Canali G, Tisne-Dessus D, Devidas A, Chevojon P, Turpault I, Lafeuillade A, Cheret A, Philip G, Stein A, Ravault I, Chavanet C, Buisson M, Treuvetot S, Choutet P, Nau P, Bastides F, May T, Boyer L, Wassoumbou S, Bernard L, De Truchis P, Berthe H, Domart Y, Merrien D, Mignot A, Greder Belan A, Gayraud M, Bodard L, Meudec A, Beuscart C, Daniel C, Pape E, Mourier L, Vinceneux P, Simonpoli AM, Zeng A, Jacquet M, Fournier L, Fuzibet JG, Sohn C, Rosenthal E, Quaranta M, Dellamonica P, Chaillou S, Sabah M, Pasteur L, Audhuy B, Schieber A, Moreau P, Niault M, Vaillant O, Huchon G, Compagnucci A, De Lacroix Szmania I, Richier L, Lamaury I, Saint-Dizier F, Garipuy D, Gastaut JA, Drogoul MP, Poizot Martin I, Fabre G, Lambert de Cursay G, Abraham B, Perino C, Lagarde P, David F, Veil S, Roche-Sicot J, Saraux JL, Lepretre A, Fampin B, Uludag A, Morin AS, Bletry O, Zucman D, Regnier A, Girard JJ, Quinsat DT, Heripret L, Grihon F, Houlbert D, Ruel M, Chemlal K, Nicolle C, Caron F, Debab Y, Tremollieres F, Perronne V, Duffaut H, Lepeu G, Slama B, Perre P, Miodovski C, Guermonprez G, Dulioust A, Ballanger R, Boudon P, Malbec D, Patey O, Semaille C, Deville J, Remy G, Beguinot I, Galanaud P, Boue F, Chambrin V, Pignon C, Estocq GA, Levy A, Delfraissy JF, Goujard C, Duracinsky M, Le Bras P, Ngussan MS, Peretti D, Medintzeff N, Lambert T, Segeral O, Lezeau P, Laurian Y, Weiss L, Buisson M, Piketty C, Karmochkine M, Batisse D, Eliaszewitch M, Jayle D, Tisne-Dessus D, Kazatchkine M, Leport C, Colasante U, Jadand C, Jestin C, Duval X, Nouaouia W, Boucherit S, Vilde JL, Girard PM, Bollens D, Binet D, Diallo B, Meyohas MC, Fonquernie L, Lagneau JL, Salmon D, Guillevin L, Tahi T, Launay O, Pietrie MP, Sicard D, Stieltjes N, Michot J, Sobel A, Levy Y, Bourdillon F, Lascaux AS, Lelievre JD, Dumont C, Dupont B, Obenga G, Viard JP, Maignan A, Vittecoq D, Escaut L, Bolliot C, Bricaire F, Katlama C, Schneider L, Herson S, Simon A, Iguertsira M, Stein A, Tomei C, Ravaux I.

Author information

  • 1Harvard School of Public Health, Boston, MA, USA.

Abstract

BACKGROUND:

Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.

OBJECTIVE:

To identify the optimal CD4 cell count at which cART should be initiated.

DESIGN:

Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.

SETTING:

HIV clinics in Europe and the Veterans Health Administration system in the United States.

PATIENTS:

20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis.

MEASUREMENTS:

Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.

RESULTS:

Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.

LIMITATIONS:

CD4 cell count at cART initiation was not randomized. Residual confounding may exist.

CONCLUSION:

Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

Comment in

PMID:
21502648
[PubMed - indexed for MEDLINE]
PMCID:
PMC3610527
Free PMC Article

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