Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART Study

The Strategies for Management of Antiretroviral Therapy (SMART) Study Group

Research output: Contribution to journalArticleResearchpeer-review

306 Citations (Scopus)

Abstract

Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/μL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Methods. Patients who were either ART naive (n = 249) or who had not been receiving ART for ≤6 months (n = 228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). Results. A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for ≤6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for ≤6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; P = .02); outcome (ii), 3.26 (95% CI, 1.04-10.25; P = .04); outcome (iii), 7.02 (95% CI, 1.57-31.38; P = .01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; P = .002). Conclusions. Initiation of ART at CD4+ cell counts >350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. Trial registration. ClinicalTrials.gov identifier: NCT00027352.

Original languageEnglish
Pages (from-to)1133-1144
Number of pages12
JournalJournal of Infectious Diseases
Volume197
Issue number8
DOIs
Publication statusPublished - 15 Apr 2008

Cite this

The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. / Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART Study. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 8. pp. 1133-1144.
@article{1a272c45f32b411284d048a8213547c8,
title = "Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART Study",
abstract = "Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/μL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Methods. Patients who were either ART naive (n = 249) or who had not been receiving ART for ≤6 months (n = 228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). Results. A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for ≤6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for ≤6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95{\%} confidence interval [CI], 1.26-9.56; P = .02); outcome (ii), 3.26 (95{\%} CI, 1.04-10.25; P = .04); outcome (iii), 7.02 (95{\%} CI, 1.57-31.38; P = .01); and outcome (iv), 4.19 (95{\%} CI, 1.69-10.39; P = .002). Conclusions. Initiation of ART at CD4+ cell counts >350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. Trial registration. ClinicalTrials.gov identifier: NCT00027352.",
author = "Sean Emery and Neuhaus, {Jacqueline A.} and Phillips, {Andrew N.} and Abdel Babiker and Cohen, {Calvin J.} and J. Gatell and Girard, {Pierre Marie} and Birgit Grund and Matthew Law and Losso, {Marcelo H.} and Adrian Palfreeman and Robin Wood and F. Gordin and E. Finley and D. Dietz and C. Chesson and M. Vjecha and B. Standridge and B. Schmetter and L. Grue and M. Willoughby and A. Demers and Lundgren, {J. D.} and A. Phillips and Dragsted, {U. B.} and Jensen, {K. B.} and A. Fau and L. Borup and M. Pearson and Jansson, {P. O.} and Jensen, {B. G.} and Benfield, {T. L.} and Darbyshire, {J. H.} and Babiker, {A. G.} and Palfreeman, {A. J.} and Fleck, {S. L.} and Y. Collaco-Moraes and B. Cordwell and W. Dodds and {van Hooff}, F. and L. Wyzydrag and Cooper, {D. A.} and Drummond, {F. M.} and Connor, {S. A.} and Satchell, {C. S.} and S. Gunn and S. Oka and Delfino, {M. A.} and K. Merlin and C. McGinley and Neaton, {J. D.} and G. Bartsch and A. Duchene and M. George and M. Harri-Harrison and C. Hogan and E. Krum and G. Larson and C. Miller and R. Nelson and J. Neuhaus and Roediger, {M. P.} and T. Schultz and L. Thackeray and R. Prineas and C. Campbell and G. Perez and A. Lifson and D. Duprez and Hoy, {J. F.} and C. Lahart and D. Perlman and R. Price and F. Rhame and J. Sampson and J. Worley and Rein, {Board M.} and R. Dersimonian and Brody, {B. A.} and Daar, {E. S.} and Dubler, {N. N.} and Fleming, {T. R.} and Freeman, {D. J.} and Kahn, {J. P.} and Kim, {K. M.} and G. Medoff and Modlin, {J. F.} and R. Moellering and Murray, {B. E.} and B. Pick and Robb, {M. L.} and Scharfstein, {D. O.} and J. Sugarman and A. Tsiatis and C. Tuazon and L. Zoloth and K. Klingman and S. Lehrman and J. Lazovski and Belloso, {W. H.} and Benetucci, {J. A.} and S. Aquilia and V. Bittar and Bogdanowicz, {E. P.} and Cahn, {P. E.} and Casir{\'o}, {A. D.} and I. Cassetti and Contarelli, {J. M.} and Corral, {J. A.} and A. Crinejo and L. Daciuk and David, {D. O.} and G. Guaragna and Ishida, {M. T.} and A. Krolewiecki and Laplume, {H. E.} and Lasala, {M. B.} and L. Lourtau and Lupo, {S. H.} and A. Maranzana and F. Masciottra and M. Michaan and L. Ruggieri and E. Salazar and M. S{\'a}nchez and C. Somenzini and Rogers, {G. D.} and Allworth, {A. M.} and Anderson, {J. S.C.} and J. Armishaw and K. Barnes and A. Carr and A. Chiam and Chuah, {J. C.P.} and Curry, {M. C.} and Dever, {R. L.} and Donohue, {W. A.} and Doong, {N. C.} and Dwyer, {D. E.} and J. Dyer and B. Eu and Ferguson, {V. W.} and French, {M. A.H.} and Garsia, {R. J.} and J. Gold and Hudson, {J. H.} and S. Jeganathan and P. Konecny and J. Leung and McCormack, {C. L.} and M. McMurchie and N. Medland and Moore, {R. J.} and Moussa, {M. B.} and D. Orth and M. Piper and T. Read and Roney, {J. J.} and N. Roth and Shaw, {D. R.} and J. Silvers and Smith, {D. J.} and Street, {A. C.} and Vale, {R. J.} and Wendt, {N. A.} and H. Wood and Youds, {D. W.} and J. Zillman and A. Rieger and V. Tozeau and A. Aichelburg and N. Vetter and N. Clumeck and S. Dewit and {de Roo}, A. and K. Kabeya and P. Leonard and L. Lynen and M. Moutschen and E. O’doherty and Pereira, {L. C.} and Souza, {T. N.L.} and M. Schechter and R. Zajdenverg and Almeida, {M. M.T.B.} and F. Araujo and F. Bahia and C. Brites and Caseiro, {M. M.} and J. Casseb and A. Etzel and Falco, {G. G.} and Filho, {E. C.J.} and Flint, {S. R.} and Gonzales, {C. R.} and Madruga, {J. V.R.} and Passos, {L. N.} and T. Reuter and Sidi, {L. C.} and Toscano, {A. L.C.} and D. Zarowny and E. Cherban and J. Cohen and B. Conway and C. Dufour and M. Ellis and A. Foster and D. Haase and H. Haldane and M. Houde and C. Kato and M. Klein and B. Lessard and A. Martel and C. Martel and N. McFarland and E. Paradis and A. Piche and R. Sandre and W. Schlech and S. Schmidt and F. Smaill and B. Thompson and S. Trottier and S. Vezina and S. Walmsley and {Wolff Reyes}, {M. J.} and R. Northland and L. Ostergaard and C. Pedersen and H. Nielsen and L. Hergens and Loftheim, {I. R.} and M. Raukas and K. Zilmer and J. Justinen and M. Ristola and Girard, {P. M.} and R. Landman and S. Abel and S. Abgrall and K. Amat and L. Auperin and R. Barruet and A. Benalycherif and N. Benammar and M. Bensalem and M. Bentata and Besnier, {J. M.} and {The Strategies for Management of Antiretroviral Therapy (SMART) Study Group}",
year = "2008",
month = "4",
day = "15",
doi = "10.1086/586713",
language = "English",
volume = "197",
pages = "1133--1144",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "8",

}

Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART Study. / The Strategies for Management of Antiretroviral Therapy (SMART) Study Group.

In: Journal of Infectious Diseases, Vol. 197, No. 8, 15.04.2008, p. 1133-1144.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART Study

AU - Emery, Sean

AU - Neuhaus, Jacqueline A.

AU - Phillips, Andrew N.

AU - Babiker, Abdel

AU - Cohen, Calvin J.

AU - Gatell, J.

AU - Girard, Pierre Marie

AU - Grund, Birgit

AU - Law, Matthew

AU - Losso, Marcelo H.

AU - Palfreeman, Adrian

AU - Wood, Robin

AU - Gordin, F.

AU - Finley, E.

AU - Dietz, D.

AU - Chesson, C.

AU - Vjecha, M.

AU - Standridge, B.

AU - Schmetter, B.

AU - Grue, L.

AU - Willoughby, M.

AU - Demers, A.

AU - Lundgren, J. D.

AU - Phillips, A.

AU - Dragsted, U. B.

AU - Jensen, K. B.

AU - Fau, A.

AU - Borup, L.

AU - Pearson, M.

AU - Jansson, P. O.

AU - Jensen, B. G.

AU - Benfield, T. L.

AU - Darbyshire, J. H.

AU - Babiker, A. G.

AU - Palfreeman, A. J.

AU - Fleck, S. L.

AU - Collaco-Moraes, Y.

AU - Cordwell, B.

AU - Dodds, W.

AU - van Hooff, F.

AU - Wyzydrag, L.

AU - Cooper, D. A.

AU - Drummond, F. M.

AU - Connor, S. A.

AU - Satchell, C. S.

AU - Gunn, S.

AU - Oka, S.

AU - Delfino, M. A.

AU - Merlin, K.

AU - McGinley, C.

AU - Neaton, J. D.

AU - Bartsch, G.

AU - Duchene, A.

AU - George, M.

AU - Harri-Harrison, M.

AU - Hogan, C.

AU - Krum, E.

AU - Larson, G.

AU - Miller, C.

AU - Nelson, R.

AU - Neuhaus, J.

AU - Roediger, M. P.

AU - Schultz, T.

AU - Thackeray, L.

AU - Prineas, R.

AU - Campbell, C.

AU - Perez, G.

AU - Lifson, A.

AU - Duprez, D.

AU - Hoy, J. F.

AU - Lahart, C.

AU - Perlman, D.

AU - Price, R.

AU - Rhame, F.

AU - Sampson, J.

AU - Worley, J.

AU - Rein, Board M.

AU - Dersimonian, R.

AU - Brody, B. A.

AU - Daar, E. S.

AU - Dubler, N. N.

AU - Fleming, T. R.

AU - Freeman, D. J.

AU - Kahn, J. P.

AU - Kim, K. M.

AU - Medoff, G.

AU - Modlin, J. F.

AU - Moellering, R.

AU - Murray, B. E.

AU - Pick, B.

AU - Robb, M. L.

AU - Scharfstein, D. O.

AU - Sugarman, J.

AU - Tsiatis, A.

AU - Tuazon, C.

AU - Zoloth, L.

AU - Klingman, K.

AU - Lehrman, S.

AU - Lazovski, J.

AU - Belloso, W. H.

AU - Benetucci, J. A.

AU - Aquilia, S.

AU - Bittar, V.

AU - Bogdanowicz, E. P.

AU - Cahn, P. E.

AU - Casiró, A. D.

AU - Cassetti, I.

AU - Contarelli, J. M.

AU - Corral, J. A.

AU - Crinejo, A.

AU - Daciuk, L.

AU - David, D. O.

AU - Guaragna, G.

AU - Ishida, M. T.

AU - Krolewiecki, A.

AU - Laplume, H. E.

AU - Lasala, M. B.

AU - Lourtau, L.

AU - Lupo, S. H.

AU - Maranzana, A.

AU - Masciottra, F.

AU - Michaan, M.

AU - Ruggieri, L.

AU - Salazar, E.

AU - Sánchez, M.

AU - Somenzini, C.

AU - Rogers, G. D.

AU - Allworth, A. M.

AU - Anderson, J. S.C.

AU - Armishaw, J.

AU - Barnes, K.

AU - Carr, A.

AU - Chiam, A.

AU - Chuah, J. C.P.

AU - Curry, M. C.

AU - Dever, R. L.

AU - Donohue, W. A.

AU - Doong, N. C.

AU - Dwyer, D. E.

AU - Dyer, J.

AU - Eu, B.

AU - Ferguson, V. W.

AU - French, M. A.H.

AU - Garsia, R. J.

AU - Gold, J.

AU - Hudson, J. H.

AU - Jeganathan, S.

AU - Konecny, P.

AU - Leung, J.

AU - McCormack, C. L.

AU - McMurchie, M.

AU - Medland, N.

AU - Moore, R. J.

AU - Moussa, M. B.

AU - Orth, D.

AU - Piper, M.

AU - Read, T.

AU - Roney, J. J.

AU - Roth, N.

AU - Shaw, D. R.

AU - Silvers, J.

AU - Smith, D. J.

AU - Street, A. C.

AU - Vale, R. J.

AU - Wendt, N. A.

AU - Wood, H.

AU - Youds, D. W.

AU - Zillman, J.

AU - Rieger, A.

AU - Tozeau, V.

AU - Aichelburg, A.

AU - Vetter, N.

AU - Clumeck, N.

AU - Dewit, S.

AU - de Roo, A.

AU - Kabeya, K.

AU - Leonard, P.

AU - Lynen, L.

AU - Moutschen, M.

AU - O’doherty, E.

AU - Pereira, L. C.

AU - Souza, T. N.L.

AU - Schechter, M.

AU - Zajdenverg, R.

AU - Almeida, M. M.T.B.

AU - Araujo, F.

AU - Bahia, F.

AU - Brites, C.

AU - Caseiro, M. M.

AU - Casseb, J.

AU - Etzel, A.

AU - Falco, G. G.

AU - Filho, E. C.J.

AU - Flint, S. R.

AU - Gonzales, C. R.

AU - Madruga, J. V.R.

AU - Passos, L. N.

AU - Reuter, T.

AU - Sidi, L. C.

AU - Toscano, A. L.C.

AU - Zarowny, D.

AU - Cherban, E.

AU - Cohen, J.

AU - Conway, B.

AU - Dufour, C.

AU - Ellis, M.

AU - Foster, A.

AU - Haase, D.

AU - Haldane, H.

AU - Houde, M.

AU - Kato, C.

AU - Klein, M.

AU - Lessard, B.

AU - Martel, A.

AU - Martel, C.

AU - McFarland, N.

AU - Paradis, E.

AU - Piche, A.

AU - Sandre, R.

AU - Schlech, W.

AU - Schmidt, S.

AU - Smaill, F.

AU - Thompson, B.

AU - Trottier, S.

AU - Vezina, S.

AU - Walmsley, S.

AU - Wolff Reyes, M. J.

AU - Northland, R.

AU - Ostergaard, L.

AU - Pedersen, C.

AU - Nielsen, H.

AU - Hergens, L.

AU - Loftheim, I. R.

AU - Raukas, M.

AU - Zilmer, K.

AU - Justinen, J.

AU - Ristola, M.

AU - Girard, P. M.

AU - Landman, R.

AU - Abel, S.

AU - Abgrall, S.

AU - Amat, K.

AU - Auperin, L.

AU - Barruet, R.

AU - Benalycherif, A.

AU - Benammar, N.

AU - Bensalem, M.

AU - Bentata, M.

AU - Besnier, J. M.

AU - The Strategies for Management of Antiretroviral Therapy (SMART) Study Group

PY - 2008/4/15

Y1 - 2008/4/15

N2 - Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/μL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Methods. Patients who were either ART naive (n = 249) or who had not been receiving ART for ≤6 months (n = 228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). Results. A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for ≤6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for ≤6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; P = .02); outcome (ii), 3.26 (95% CI, 1.04-10.25; P = .04); outcome (iii), 7.02 (95% CI, 1.57-31.38; P = .01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; P = .002). Conclusions. Initiation of ART at CD4+ cell counts >350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. Trial registration. ClinicalTrials.gov identifier: NCT00027352.

AB - Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/μL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Methods. Patients who were either ART naive (n = 249) or who had not been receiving ART for ≤6 months (n = 228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). Results. A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for ≤6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for ≤6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; P = .02); outcome (ii), 3.26 (95% CI, 1.04-10.25; P = .04); outcome (iii), 7.02 (95% CI, 1.57-31.38; P = .01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; P = .002). Conclusions. Initiation of ART at CD4+ cell counts >350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. Trial registration. ClinicalTrials.gov identifier: NCT00027352.

UR - http://www.scopus.com/inward/record.url?scp=42549121220&partnerID=8YFLogxK

U2 - 10.1086/586713

DO - 10.1086/586713

M3 - Article

VL - 197

SP - 1133

EP - 1144

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 8

ER -