Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study

Role of CD4+ cell counts and HIV RNA levels during follow-up

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

Research output: Contribution to journalArticleResearchpeer-review

158 Citations (Scopus)

Abstract

Background and methods. The SMART study compared 2 strategies for using antiretroviral therapy - drug conservation (DC) and viral suppression (VS) - in 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. Results. During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/μL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count <350 cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count ≥350 cells/μL - an increase explained by the higher HIV RNA levels in the DC group. Conclusions. The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death. Trial registration. Clinical Trials.gov identifier: NCT00027352.

Original languageEnglish
Pages (from-to)1145-1155
Number of pages11
JournalJournal of Infectious Diseases
Volume197
Issue number8
DOIs
Publication statusPublished - 15 Apr 2008

Cite this

@article{e43134a880b847c187467fee40bf4151,
title = "Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: Role of CD4+ cell counts and HIV RNA levels during follow-up",
abstract = "Background and methods. The SMART study compared 2 strategies for using antiretroviral therapy - drug conservation (DC) and viral suppression (VS) - in 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. Results. During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/μL (for DC vs. VS, 31{\%} vs. 8{\%}) and with a latest HIV RNA level >400 copies/mL (71{\%} vs. 28{\%}) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count <350 cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95{\%} confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count ≥350 cells/μL - an increase explained by the higher HIV RNA levels in the DC group. Conclusions. The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death. Trial registration. Clinical Trials.gov identifier: NCT00027352.",
author = "Lundgren, {Jens D.} and Abdel Babiker and Wafaa El-Sadr and Sean Emery and Birgit Grund and Neaton, {James D.} and Jacquie Neuhaus and Phillips, {Andrew N.} 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 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 Hoff}, F. and L. Wazydrag 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 A. Duchene and M. Harrison and M. George and C. Hogan and E. Krum and G. Larson and C. Miller and R. Nelson 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 M. Rein 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 Losso, {M. 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 Hoy, {J. F.} and Rogers, {G. D.} and Allworth, {A. M.} and Anderson, {J. St 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 {Rone Y}, {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 {Youd S}, {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 M. Blanc and O. Bouchaud and A. Cabi{\'e} and P. Chavannet and Chennebault, {J. M.} and S. Dargere and {de la Tribonniere}, X. and {The Strategies for Management of Antiretroviral Therapy (SMART) Study Group}",
year = "2008",
month = "4",
day = "15",
doi = "10.1086/529523",
language = "English",
volume = "197",
pages = "1145--1155",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "8",

}

Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study : Role of CD4+ cell counts and HIV RNA levels during follow-up. / The Strategies for Management of Antiretroviral Therapy (SMART) Study Group.

In: Journal of Infectious Diseases, Vol. 197, No. 8, 15.04.2008, p. 1145-1155.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study

T2 - Role of CD4+ cell counts and HIV RNA levels during follow-up

AU - Lundgren, Jens D.

AU - Babiker, Abdel

AU - El-Sadr, Wafaa

AU - Emery, Sean

AU - Grund, Birgit

AU - Neaton, James D.

AU - Neuhaus, Jacquie

AU - Phillips, Andrew N.

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 - 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 Hoff, F.

AU - Wazydrag, 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 - Duchene, A.

AU - Harrison, M.

AU - George, M.

AU - Hogan, C.

AU - Krum, E.

AU - Larson, G.

AU - Miller, C.

AU - Nelson, R.

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, 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 - Losso, M. 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 - Hoy, J. F.

AU - Rogers, G. D.

AU - Allworth, A. M.

AU - Anderson, J. St 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 - Rone Y, 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 - Youd S, 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 - Blanc, M.

AU - Bouchaud, O.

AU - Cabié, A.

AU - Chavannet, P.

AU - Chennebault, J. M.

AU - Dargere, S.

AU - de la Tribonniere, X.

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

PY - 2008/4/15

Y1 - 2008/4/15

N2 - Background and methods. The SMART study compared 2 strategies for using antiretroviral therapy - drug conservation (DC) and viral suppression (VS) - in 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. Results. During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/μL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count <350 cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count ≥350 cells/μL - an increase explained by the higher HIV RNA levels in the DC group. Conclusions. The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death. Trial registration. Clinical Trials.gov identifier: NCT00027352.

AB - Background and methods. The SMART study compared 2 strategies for using antiretroviral therapy - drug conservation (DC) and viral suppression (VS) - in 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. Results. During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/μL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count <350 cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count ≥350 cells/μL - an increase explained by the higher HIV RNA levels in the DC group. Conclusions. The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death. Trial registration. Clinical Trials.gov identifier: NCT00027352.

UR - http://www.scopus.com/inward/record.url?scp=42549131481&partnerID=8YFLogxK

U2 - 10.1086/529523

DO - 10.1086/529523

M3 - Article

VL - 197

SP - 1145

EP - 1155

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 8

ER -