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

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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 (US)
Pages (from-to)1145-1155
Number of pages11
JournalJournal of Infectious Diseases
Volume197
Issue number8
DOIs
StatePublished - Apr 15 2008
Externally publishedYes

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CD4 Lymphocyte Count
HIV
RNA
Pharmaceutical Preparations
Virus Replication
Therapeutics
Wiskott-Aldrich Syndrome
Clinical Trials
Confidence Intervals
Drug Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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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 journalArticle

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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 = "{The Strategies for Management of Antiretroviral Therapy (SMART) Study Group} and 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 Rodriguez, {Allan E}",
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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 - The Strategies for Management of Antiretroviral Therapy (SMART) Study Group

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 - Rodriguez, Allan E

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.

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DO - 10.1086/529523

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