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Lancet HIV. 2015 Aug;2(8):e335-43. doi: 10.1016/S2352-3018(15)00108-3. Epub 2015 Jul 7.

Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

Collaborators (1250)

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, Walsh J, 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, Bulbeck S, Mandalia S, Clarke J, Anderson J, Munshi S, Post F, Easterbrook P, Khan Y, Patel P, Karim F, Duffell S, Gilson R, Williams I, Gompels M, Dooley D, Schwenk A, Ainsworth J, Johnson M, Youle M, Lampe F, Chaloner C, Puradiredja DI, Bansi L, Hill T, Phillips A, Sabin C, Walsh J, Weber J, Kemble C, Mackie N, Winston A, Leen C, Wilson A, Reiss P, Bezemer DO, Kesselring AM, van Sighem AI, Smit C, Zaheri S, Kortmann W, Prins JM, Kuijpers TW, Godfried MH, Reiss P, Pajkrt D, Bos JC, van der Valk M, Grijsen ML, Wiersinga WJ, Vrouwe L, Brinkman K, Blok WL, Ziekenhuis A, Veenstra J, Lettinga KD, Mulder JW, Lauw FN, van Agtmael MA, Perenboom RM, Bomers M, Richter C, van der Berg JP, Gisolf EH, Schippers EF, van Elzakker EP, Bravenboer B, Kootstra GJ, Sprenger HG, Doedens R, van Assen S, Gasthuis K, Soetekouw R, Kroon FP, van Dissel JT, Arend SM, Jolink H, Bauer MP, Weijer S, Lowe S, Lashof AO, Posthouwer D, Koopmans PP, Warris A, van Crevel R, Nouwen JL, Nispen MH, Verbon A, Hassing RJ, Hartwig NG, Ziekenhuis M, Pogany K, Ziekenhuis SE, Juttmann JR, van Kasteren ME, Mudrikova T, Ellerbroek PM, Oosterheert JJ, Barth RE, Kinderziekenhuis W, Bont LJ, De Ruyter Ziekenhuis A, Stegeman A, Alleman MA, Bouwhuis JW, Abgrall S, Barin F, Bentata M, Billaud E, Boué F, Burty C, Cabié A, De Truchis P, Duval X, Duvivier C, Enel P, Fredouille-Heripret L, Gasnault J, Gaud C, Katlama C, Khuong MA, Lang JM, Lascaux AS, Launay O, Mahamat A, Mary-Krause M, Meynard JL, Pavie J, Pialoux G, Pilorgé F, Poizot-Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tissot-Dupont H, Viard JP, Viget N, Jacquemet N, Abgrall S, Costagliola D, Grabar S, Guiguet M, Lanoy E, Lièvre L, Mary-Krause M, Lacombe JM, Potard V, Pitié GH, Bricaire F, Herson S, Katlama C, Simon A, Desplanque N, Meyohas MC, Picard O, Cadranel J, Mayaud C, Pialoux G, Clauvel JP, Decazes JM, Gerard L, Molina JM, Lariboisière-Fernand GH, Bentata M, Honoré P, Jeantils V, Tassi S, Mechali D, Taverne B, Bouvet E, Ecobichon JL, Matheron S, Picard-Dahan C, Yeni P, Dupont C, Chandemerle C, Mortier E, Tisne-Dessus D, Weiss L, Tarnier-Cochin GH, Auperin I, Gilquin J, Roudière L, Viard JP, Boué F, Fior R, Delfraissy JF, Goujard C, Jung C, Vittecoq D, Fraisse P, Lang JM, Beck-Wirth G, Stahl JP, Lecercq P, Gourdon F, Laurichesse H, Fresard A, Basse-Normandie C, Bazin C, Verdon R, Bourgogne C, Bretagne C, Arvieux C, Michelet C, Goudeau A, Maître MF, Hoen B, Faller JP, Haute-Normandie C, Borsa-Lebas F, Caron F, Reynes J, Daures JP, Lorraine C, May T, Rabaud C, Berger JL, Rémy G, Arlet-Suau E, Cuzin L, Massip P, Legrand MF, Pontonnier G, de Calais CN, Viget N, Yasdanpanah Y, Dellamonica P, Pradier C, Pugliese P, Quinsat D, Ravaux I, Tissot H, Delmont JP, Moreau J, Gastaut JA, Poizot-Martin I, Retornaz F, Soubeyrand J, Galinier A, Ruiz JM, Allegre T, Blanc PA, Bonnet D, Lepeu G, Granet-Brunello P, Esterni JP, Cohen-Valensi R, Nezri M, Chadapaud S, Laffeuillade A, Billaud E, Raffi F, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Strobel M, Saint-Martin CH, Bissuel F, Pradinaud R, Sobesky M, Martinique C, Guyon F, Gaud C, Contant M, HC B, CA F, HH H, de Tejada B M, Casabona J, Miró JM, de Barcelona-Idibaps C, Gallois A, Casabona J, Gallois A, Esteve A, Podzamczer D, Murillas J, Gatell JM, Manzardo C, Tural C, Clotet B, Ferrer E, Riera M, Segura F, Navarro G, Vilaró J, Masabeu A, García I, Guadarrama M, Cifuentes C, Dalmau D, Agustí C, Esteve A, Montoliu A, Pérez I, Pérez I, Gargoulas F, Blanco JL, Garcia-Alcaide F, Martínez E, García-Goez JF, Sirera G, Negredo E, Miranda C, Capitan MC, Saumoy M, Imaz A, Tiraboschi JM, Murillo O, Bolao F, Peña C, Cabellos C, Vila A, Sala M, Cervantes M, Amengual J, Navarro M, Barrufet P, Molina J, Guadarrama M, Alvaro M, Mercadal J, Fernández J, Ospina JE, Berenguer J, García F, Gutiérrez F, Labarga P, Moreno S, Caro-Murillo AM, Sobrino P, Jarrín I, Sirvent JL, Rodríguez P, Alemán MR, Alonso MM, López AM, Hernández MI, Soriano V, Labarga P, Barreiro P, Medrano J, Rivas P, Herrero D, Blanco F, Vispo ME, Martín L, Ramírez G, Rubio R, Pulido F, Moreno V, Cepeda C, Iribarren JA, Camino X, Rodríguez-Arrondo F, von Wichmann MA, Pascual L, Goenaga MA, Gutiérrez F, Masiá M, Ramos JM, Padilla S, Sánchez-Hellín V, Bernal E, Montolio F, Peral Y, Marañón G, Berenguer J, López JC, Miralles P, Cosín J, Sánchez M, Gutiérrez I, Ramírez M, Padilla B, Vidal F, Veloso S, Viladés C, López-Dupla M, Olona M, Vargas M, Lacruz J, Salavert M, Montero M, Cuéllar S, Sanz J, Oteo JA, Blanco JR, Ibarra V, Metola L, Sanz M, Pérez-Martínez L, Sola J, Uriz J, Castiello J, Reparaz J, Arriaza MJ, Irigoyen C, Moreno S, Antela A, Casado JL, Dronda F, Moreno A, Pérez MJ, López D, Gutiérrez C, Martí P, García L, Page C, García F, Hernández J, Peña A, Muñoz L, Parra J, Viciana P, Leal M, López-Cortés LF, Mata R, Justice AC, Rimland D, Jones-Taylor C, Oursler KA, Brown S, Garrison S, Rodriguez-Barradas M, Masozera N, Goetz M, Leaf D, Simberkoff M, Blumenthal D, Leung J, Peck R, Mattocks K, Braithwaite S, Cook R, Conigliaro J, Crothers K, Chang J, Crystal S, Day N, Erdos J, Freiberg M, Kozal M, Gerschenson M, Good B, Gordon A, Goulet JL, Hernán MA, Kraemer K, Lim J, Maisto S, O'Connor P, Papas R, Robins JM, Rinaldo C, Roberts M, Samet J, Tierney B, Whittle J, Phillips A, Babiker A, Brettle R, 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, Ewings F, Fairbrother K, Gnatiuc L, Lodi S, Murphy B, Douglas G, Kennedy N, Pritchard J, Andrady U, Gwynedd Y, 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, Carne C, Browing M, Stanley B, O'Mahony C, Fraser P, Hayman B, Joshi U, Ralph S, Wade A, Mette R, Lalik J, Summerfield H, El-Dalil A, France AJ, White C, Robertson R, Gordon S, Lean C, Morris S, Vithayathil K, McLean L, Winter A, Gale D, Jacobs S, Tayal S, Short L, Roberts M, Williams G, Minton J, Dhar J, Nye F, DeSouza CB, Isaksen A, McDonald L, McLean K, Franca A, Hawkins D, William L, Peters B, El 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, Cook J, Haynes J, Keynes M, Evans E, Ong E, Das R, Grey R, Meaden J, Bignell C, Loay D, Peacock K, Eliot G, Girgis MR, Morgan B, Palfreeman A, Wilcox J, Tobin J, Tucker L, Saeed AM, Williams O, Clwyd G, Lacey H, Herman S, Kinghorn D, Devendra SV, Wither J, Dawson S, Rowen D, Harvey J, Wilkins E, Chauhan M, Kellock D, Young S, Dannino S, Kathir Y, Rooney G, Currie J, Fitzgerald M, Devendra S, Keane F, Booth G, Arumainayyagam J, Chandramani S, Robinson T, Curless E, Gokhale R, Tariq A, Roberts M, Williams O, Luzzi G, FitzGerald M, Fairley I, Wallis F, Smit E, Ward F, Molina JM, Loze B, Morlat P, Bonarek M, Bonnet F, Nouts C, Louis I, Raffi F, Reliquet V, Sauser F, Biron C, Mounoury O, Hue H, Brosseau D, Goujard C, Ghosn J, Rannou MT, Bergmann JF, Badsi E, Rami A, Girard PM, Samanon-Bollens D, Campa P, Tourneur M, Desplanques N, Livrozet JM, Jeanblanc F, Chiarello P, Makhloufi D, Herriot E, Blanc AP, Allègre T, Reynes J, Baillat V, Lemoing V, de Boever CM, Tramoni C, Cabié A, Sobesky G, Abel S, Beaujolais V, Pialoux G, Slama L, Yeni P, Bouvet E, Fournier I, Gerbe J, Trepo C, Koffi K, Miailhes P, Thoirain V, Brochier C, Thomas R, Souala F, Ratajczak M, Beytoux J, Jacomet C, Gourdon F, Montpied G, Rouveix E, Olivier C, Paré A, Lortholary O, Dupont B, Viard JP, Maignan A, Raymond I, Leport C, Jadand C, Jestin C, Longuet P, Boucherit S, Sereni D, Lascoux C, Prevoteau F, Sobel A, Levy Y, Lelièvre JD, Lascaux AS, Mondor H, Aumaître H, Delmas B, Saada M, Medus M, Salmon D, Tahi T, Yazdanpanah Y, Pavel S, Marien MC, Dron CH, Beck C, Benomar M, Muller E, Katlama C, Tubiana R, Mohand HA, Bentata M, Touam F, Hoen B, Folzer A, Massip P, Obadia M, Prudhomme L, Bonnet E, Balzarin F, Pichard E, Chennebault JM, Fialaire P, Loison J, Galanaud P, Boué F, Bornarel D, Verdon R, Bazin C, Six M, Ferret P, Weiss L, Batisse D, Tisne-Dessus D, Devidas A, Chevojon P, Turpault I, Philip G, Morel P, Timsit J, Herson S, Amirat N, Cabane J, Picard O, Tredup J, Desplanques N, Chavanet C, Buisson M, Treuvetot S, Choutet P, Bastides F, May T, Boyer L, Wassoumbou S, Oksenhendeler E, Gérard L, Bernard L, De Truchis P, Berthé H, Poincaré R, Domart Y, Merrien D, Belan AG, Mignot A, Gayraud M, Bodard L, Meudec A, Pape E, Vinceneux P, Simonpoli AM, Zeng A, Mourier L, Fournier L, Jacquet M, Fuzibet JG, Sohn C, Rosenthal E, Quaranta M, Sabah M, Audhuy B, Schieber A, Pasteur L, Moreau P, Vaillant O, Huchon G, Compagnucci A, De Lacroix Szmania I, Lamaury I, Saint-Dizier F, Garipuy D, Gastaut JA, Drogoul MP, Martin IP, Fabre G, Lambert G, Lagarde P, David F, Roche-Sicot J, Saraux JL, Leprêtre A, Veil S, 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, Caron F, Debab Y, Nicolle C, Perronne V, Quesnay F, Lepeu G, Slama B, Duffaut H, Perré P, Miodovski C, Guermonprez G, Dulioust A, Ballanger R, Patey O, Semaille C, Deville J, Beclere A, Galanaud P, Boue F, Chambrin V, Pignon C, Estocq GA, Levy A, Bicetre le K, Delfraissy JF, Goujard C, Duracinsky M, Bras PL, Ngussan MS, Lambert T, Segeral O, Lezeau P, Laurian Y, Piketty C, Karmochkine M, Batisse D, Eliaszewitch M, Jayle D, Tisne D, Leport C, Colasante U, Jadand C, Jestin C, Duval X, Boucherit S, Vilde JL, Girard PM, Bollens D, Binet D, Diallo B, Lagneau JL, Salmon D, Tahi T, Launay O, Pietrie MP, Sicard D, Stieltjes N, Michot J, Sobel A, Levy Y, Bourdillon F, Lascaux AS, Dupont B, Obenga G, Viard JP, Maignan A, Vittecoq D, Escaut L, Bolliot C, Bricaire F, Katlama C, Schneider L, Iguertsira M, Stein A, Tomei C, Ravaux I, Dhiver C, Gallais J, Gallais H, Gastaut JA, Drogoul MP, Dellamonica P, Durant J, Mondain V, Perbost I, Cassuto JP, Karsenti JM, Fuzibet JG, Rosenthal E, Ceppi C, Quaranta M, Krivitsky JA, Bentata M, Honore P, Sereni D, Lascoux C, Delgado J, Rouzioux C, Burgard M, Boufassa L, Peynet J, Pérez-Hoyos S, Schiaffino A, Monge DA, Pujol I, Muga R, Sanvisens A, Clotet B, Tor J, Bolao F, Rivas I, Vallecillo G, del Romero J, Raposo P, Rodríguez C, Vera M, Alastrue EF, Tasa CS, Juan A, Trullen J, de Olalla PG, Cayla J, Sambeat MA, Guerrero R, Rivera E, Guerrero R, Marco A, Quintana M, Gonzalez C, Castilla J, Guevara M, de Mendoza C, Zahonero N, Ortíz M, G D, T K, G P, H S, M C, G P, Schwenk A, Bansi L, Nelson M, Asboe D, Delpech V, Man SL, Smith C, Grabowska H, Gras LA, Branger J, Scherpbier HJ, van der Meer JT, Wit FW, van der Poll T, Nellen FJ, Lange JM, Geerlings SE, van Vugt M, Frissen PH, Schouten WE, van den Berk GE, Vrouenraets SM, van Eeden A, Verhagen DW, Claessen FA, Peters EJ, van Nieuwkoop C, Leyten EM, Gelinck LB, Ziekenhuis C, Pronk MJ, Delsing CE, Scholvinck EH, Bierman WF, ten Kate RW, de Boer MG, ter Vollaard HJ, Zuiderzee MC, Schreij G, Keuter M, van der Ven AJ, ter Hofstede HJ, Dofferhoff AS, van der Ende ME, de Vries-Sluijs TE, Schurink CA, Rijnders BJ, van Gorp EC, Smeulders AW, den Hollander JG, Hoepelman AI, Schneider MM, Jaspers CA, Arends JE, Wassenberg MW, Geelen SP, Wolfs T, Costagliola D, Cotte L, Gilquin J, Grabar S, Matheron S, Tattevin P, Selinger-Leneman H, Girard PM, Meynard JL, Diemer M, Sellier P, Crickx B, Berthé H, de Truchis P, Salmon D, Lesprit P, Rey D, Lucht F, Chavanet P, Choutet P, Eglinger P, Aleksandrowicz K, Pelissier L, Aubert V, Barth J, Battegay M, Bernasconi E, Böni J, Burton-Jeangros C, Calmy A, Cavassini M, Egger M, Elzi L, Fehr J, Fellay J, Furrer H, Gorgievski M, Günthard H, Hasse B, Hösli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kovari H, Ledergerber B, Martinetti G, Metzner K, Müller N, Nadal D, Pantaleo G, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schöni-Affolter F, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S, Miró JM, Force L, Mallolas J, López-Dieguez M, Romeu J, Jou A, Masó M, Bejarano G, del Amo J, Muñoz MA, Arrizabalaga AJ, Aramburu MJ, Escolano C, Sanjuan M, Peraire J, Aldeguer JL, Blanes M, de los Santos I, Hernández B, Pumares M, Trastoy M, Fiellin DA, Titanji R, Butt A, Brandt C, Bryant K, Gandhi N, Gaziano M, Miller P, Mole L, Darbyshire J, Cursley A, Eduards S, Das R, Estreich S, Magdy A, Jebakumar SP, McMillan S, Morris S, Green S, Sivakumar K, Monteiro E, Jendrulek I, Deheragada A, Rajamanoharan S, Delfraissy JF, Diemer M, Parrinello M, Chakvetadze C, Berrebi V, Dupont C, Augustin-Normand C, Morelon S, Ragnaud JM, Dominguez S, Dumont C, Drenou B, Beck-Wirth G, Drobacheff C, Gonzales-Canali A, Cheret A, Simon A, Brancion C, Stein A, Ravault I, Nau P, Beuscart C, Daniel C, Dellamonica P, Chaillou S, Niault M, Richier L, Abraham B, Perino C, Tremollieres F, Boudon P, Malbec D, Remy G, Béguinot I, Peretti D, Medintzeff N, Weiss L, Buisson M, Kazatchkine M, Meyohas MC, Fonquernie L, Lelievre JD, Dumont C, Herson S, Simon A, Tissot Dupont H, Vallon A, Fabre G, Venti H, Bouchaud O, Muga R, del Amo J, Hurtado I, Belda J, Gargalianos-Kakolyris P, Katsarou O, Lazanas M, Paparizos V, Paraskevis D, Skoutelis A, Touloumi G, Pantazis N, Bakoyannis G, Gioukari V, Antoniadou A, Papadopoulos A, Petrikkos G, Daikos G, Psichogiou M, Gargalianos-Kakolyris P, Xylomenos G, Katsarou O, Kouramba A, Ioannidou P, Kordossis T, Kontos A, Lazanas M, Tsogas N, Paparizos V, Leuow K, Kourkounti S, Sambatakou H, Mariolis I, Skoutelis A, Papastamopoulos V, Baraboutis I.

Abstract

BACKGROUND:

Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.

METHODS:

We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.

FINDINGS:

Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).

INTERPRETATION:

The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.

FUNDING:

National Institutes of Health.

PMID:
26423376
PMCID:
PMC4643831
DOI:
10.1016/S2352-3018(15)00108-3
[Indexed for MEDLINE]
Free PMC Article

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